Essences of clinical medicine.

Cardiology / 循環器科

Pulmonology/ 呼吸器科

Gastroenterology / 消化器科

Endocrinology / 内分泌科

Nephrology / 腎臓科

Hematology / 血液科

Rheumatology / リウマチ科

Infectious Diseases / 感染症科

Neurology / 神経科

Psychiatry / 精神科

Ophthalmology / 眼科

Otolaryngology / 耳鼻咽喉科

Dermatology / 皮膚科

Pigmentation Disorder / 色素疾患

Freckle / 雀卵斑

• Overview
  • Enhanced pigment production/transfer of melanocytes
• Subjective
  • Small brown macules on face, darken/fade in summer/winter
• Assessment
  • [Related] Melasma: Tan discolorization on face, often in reproductive woman
  • [Association] Suspect neurofibromatosis: If >=6 larger macules (cafe-au-lait spot)

Lentigo / 黒子

• Overview
  • Benign localized hyperplasia of melanocytes
• Subjective
  • Oval tan-brown macule/patch
• Objective
  • [Pathology] Linear melanocytic hyperplasia above basement membrane
• Assessment
  • [Related] Senile lentigo: Hyperpigmentation due to aging

Melanocytic Nevus / 色素性母斑

• Overview
  • Benign neoplasm of melanocytes
  • Mostly due to activating mutation in RAS signaling pathway
• Subjective
  • Tan to brown, uniformly pigmented, well-defined small macules
• Objective
  • [Pathology] Nests or cords of nevus cells: Progress from dermoepidermal junction (junctional) to dermis (compound) and loss in epidermis (intradermal)
• Assessment
  • [Variant] Congenital nevus: Large variants have increased melanoma risk
  • [Variant] Blue nevus: Black-blue nodule
  • [Variant] Spitz nevus: Red-pink nodule
  • [Variant] Halo nevus: Depigmentation of nevus due to Immune response against nevus cells
  • [Variant] Dysplastic nevus: Potential marker or precursor of melanoma
  • [Related] Nevus of Ota: Blue discoloration in periorbital region from birth
  • [Related] Mongolian spot: Blue discoloration in lumbosacral region from birth
• Plan
  • Observation
  • Surgical excision: If malignant risk

Melanoma / 悪性黒色腫

• Overview
  • Malignant neoplasm of melanocytes, related to UV light
  • Mutations include CDKN2A, RAF/RAS, TERT promoter
• Subjective
  • Macules characterized by “ABCDE”: Asymmetry, Border irregularity, Color variegation, Diameter enlargement, Evolution
• Objective
  • [Dermoscopy] Parallel ridge pattern, atypical pigment network: Extensive melanocyte proliferation
  • [Pathology] Nests of atypical cells with enlarged nuclei, prominent nucleoli, increased mitosis: Initial radial growth, later vertical growth
• Assessment
  • [Type] Acral lentiginous melanoma: Unrelated to sun exposure, most common in Asian/Africa
  • [Type] Superficial spreading melanoma: Related to sun exposure, most common in Western world
  • [Type] Nodular melanoma: Vertical growth
  • [Type] Lentigo maligna melanoma: indolent growth over decades
  • [Staging] T1: < 1mm, T2: <2mm, T3: <4mm, T4: >4mm
  • [Related] Merkel cell carcinoma: Malignant neoplasm from Merkel cell (sensory cell from neural crest)
• Plan
  • Surgical resection, sentinel lymph node biopsy, lymph node dissection
  • Anti-CTLA4, anti-PD1: Melanoma is inherently immunogenic
  • BRAF inhibitor, MEK inhibitor: Inhibit RAS signaling pathway

Vitiligo Vulgaris / 尋常性白斑

• Overview
  • Pigment loss due to melanocyte loss, may be due to autoimmune melanocyte destruction or nerve innervation abnormality
• Subjective
  • Well-demarcated zone of pigment loss
• Assessment
  • [Type] Segmental: Following dermatome
  • [Type] Non-segmental: Not following dermatome
• Plan
  • Topical steroid
  • UVB

Benign Epithelial Tumor / 良性上皮腫瘍

Seborrheic Keratosis / 脂漏性角化症

• Overview
  • Benign proliferation of keratinocytes, frequent in older individuals
  • Often due to activating mutation in FGFR3
• Subjective
  • Well-demarcated, tan to dark brown plaque with granular surface
• Objective
  • [Pathology] Basaloid cells with melanin pigmentation, keratin-filled cyst (horn cyst)
• Assessment
  • [Association] Suspect gastrointestinal malignancy: If suddenly appear in large numbers (Leser-Trelat sign)
  • [Related] Porokeratosis: Keratinocyte proliferation with annular ridge
  • [Related] Epidermal nevus: Keratinocyte proliferation from birth

Acanthosis Nigricans / 黒色表皮腫

• Overview
  • Hyperplasia of keratinocytes
  • Causes include inheritance, obesity, diabetes, malignancy (especially gastrointestinal)
  • Often due to FGFR3 mutation (familial), IGF1R activation (diabetes), EGFR activation (malignancy)
• Subjective
  • Thickened hyperpigmented rough skin in flexural areas
• Objective
  • [Pathology] Papillomatosis, hyperkeratosis, hyperpigmentation

Fibroepithelial Polyp / 軟性線維腫

• Overview
  • Benign skin hyperplasia (skin tag)
• Subjective
  • Soft and flesh-colored tumor, often with stalk
• Objective
  • [Pathology] Fibrovascular core covered by benign epithelium

Epidermal Cyst / 表皮囊腫

• Overview
  • Invagination and cystic expansion of epidermis or hair follicle
• Subjective
  • Skin-colored, dome-shaped nodule
  • Painful if inflamed
• Objective
  • [Pathology] Keratin-filled cyst with epidermal wall

Appendage Tumor / 付属器腫瘍

• Overview
  • Neoplasm arising from or differentiating toward skin appendage, mostly benign
• Assessment
  • [Type] Pilomatrixoma: Resembling germinal portion of hair bulb
  • [Type] Trichoepithelioma: Resembling primitive hair follicle
  • [Type] Syringoma, eccrine poroma: Resembling eccrine gland
  • [Type] Apocrine carcinoma: Resembling apocrine gland
  • [Type] Cylindroma: Resembling eccrine/apocrine duct
  • [Type] Sebaceous adenoma: Resembling sebaceous gland
  • [Related] Sebaceous nevus: Sebaceous gland proliferation from birth

Malignant Epithelial Tumor / 悪性上皮腫瘍

Actinic Keratosis / 日光角化症

• Overview
  • Precancerous neoplasm of keratinocytes due to UV light, may progress to SCC
• Subjective
  • Tan-brown to red macule with scale/horn
• Objective
  • [Pathology] Hyperplasia of atypical basal cell, parakeratosis, elastosis
• Assessment
  • [Related] Bowen disease: Full-thickness atypia, not limited to sun-exposed sites
• Plan
  • Surgical resection, freezing
  • Topical imiquimod: Activate TLR and innate immune response

Extramammary Paget Disease / 乳房外Paget病

• Overview
  • Malignant neoplasm of Paget cell within epidermis (intraepidermal adenocarcinoma)
• Subjective
  • Large erythematous and erosive patch on external genitalia
• Objective
  • [Pathology] Large cell with clear cytoplasm (Paget cell) within epidermis
• Plan
  • Wide excision

Squamous Cell Carcinoma / 有棘細胞癌

• Overview
  • Malignant neoplasm of keratinocytes due to UV light (and immunosuppression, chronic ulcer, burn scar)
  • Mutation in TP53 and RAS/NOTCH signaling pathway
• Subjective
  • Red nodule/plaque with scale, sometimes with ulceration
• Objective
  • [Pathology] Atypical keratinocytes with variable differentiation, keratin pearl, dermal invasion
• Assessment
  • [Variant] Keratoacanthoma: Dome-shaped tumor with central keratinous plug, well-differentiated SCC that often spontaneously regress
• Plan
  • Surgical resection
  • Radiotherapy

Basal Cell Carcinoma / 基底細胞癌

• Overview
  • Malignant neoplasm of basaloid cell, related to UV light
  • Due to mutation in Hedgehog signaling pathway (often PTCH)
• Subjective
  • Brown to black pearly papules/nodules, sometimes with ulceration
• Objective
  • [Dermoscopy] Telangiectasias, multifocal or nodular growth
  • [Pathology] Nests of basaloid cells, peripheral palisading, artificial cleft
• Assessment
  • Locally aggressive but slow growing and rarely metastasize
• Plan
  • Surgical resection

Dermal Tumor / 真皮腫瘍

Dermatofibroma / 皮膚線維腫

• Overview
  • Benign neoplasm of fibroblast and histiocyte
• Subjective
  • Tan to brown firm papule/nodule
• Objective
  • [Pathology] Benign spindle cells in dermis, overlying epidermal hyperplasia

Dermatofibrosarcoma Protuberans / 隆起性皮膚線維肉腫

• Overview
  • Malignant neoplasm of fibroblast
  • Locally aggressive but slow growing and rarely metastasize
  • Due to COL1A1-PDGFB translocation, lead to increased PDGFβ secretion
• Subjective
  • Firm protuberant nodule
• Objective
  • [Pathology] Storiform fibroblast, often extend to subcutaneous fat
• Plan
  • Surgical resection

Mycosis Fungoides / 菌状息肉症

• Overview
  • Malignant neoplasm of CD4+ T-helper cells involving skin (cutaneous T cell lymphoma)
  • Localized to skin initially, may evolve to systemic lymphoma after years
• Subjective
  • Multiple erythematous patches: Erythematous stage
  • Red to brown scaling plaques: Plaque stage
  • Brown ulcerated nodule: Tumor stage
• Objective
  • [Pathology] CD4+ lymphocyte infiltration, band-like in dermis, Pautrier microabscess in epidermis
• Assessment
  • [Stage] Sezary syndrome: Advanced stage with diffuse erythroderma, lymphadenopathy, circulating atypical lymphocytes
• Plan
  • Topical steroid, UV light: For early stage
  • Systemic chemotherapy: For advanced stage

Mastocytosis / 肥満細胞症

• Overview
  • Benign proliferation of mast cells in skin (urticaria pigmentosa)
  • Due to mutation in KIT (and also PDGFRA)
• Subjective
  • Multiple red-brown patches/nodules, mainly in children
  • Localized edema when lesion rubbed (Darier sign): Histamine release
  • Wheals/pruritus/flush triggered by food or temperature change: Histamine release
• Objective
  • [Pathology] Proliferation of mast cells in dermis
• Assessment
  • Spontaneous resolve in children

Vascular Tumor / 血管腫瘍

Vascular Ectasia / 血管拡張症

• Overview
  • Dilatations of capillaries/venules/arterioles, not neoplasm
• Subjective
  • [Nevus flammeus] Pink/purple patch on head/neck in infant
  • [Spider telangiectasia] Radial pulsatile lesion
• Assessment
  • [Type] Nevus flammeus: Regress spontaneously (except for port wine stain which persists)
  • [Type] Spider telangiectasia: Associated with hyper-estrogenic state
  • [Association] Sturge-Weber syndrome: Vascular ectasia of face (port wine stain), leptomenings (intellectual disability, hemiplegia), choroid plexus (glaucoma), due to GNAS mutation
  • [Association] Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease): Multiple telangiectasias on skin/mucosa, causing recurrent epistaxis

Hemangioma / 血管腫

• Overview
  • Benign neoplasm of endothelial cell with blood-filled vessels
• Subjective
  • Blood-rich tumor on skin/mucosa or viscera
• Assessment
  • [Type] Capillary hemangioma: Common, with thin-walled capillaries
  • [Type] Cavernous hemangioma: Infiltrative, with cavernous vascular space, associated with von Hippel-Lindau disease
  • [Type] Juvenile hemangioma: Common in newborn, mostly regress
  • [Type] Pyogenic granuloma: Rapidly growing pedunculated lesion, easily bleeding
  • [Complication] Kasabach-Merritt syndrome: Thrombocytopenia or DIC due to hemorrhage in hemangioma
  • [Related] Bacillary angiomatosis: Vascular proliferation in immunocompromised hosts due to Bartonella infection

Lymphangioma / リンパ管腫

• Overview
  • Benign neoplasm of lymphatic endothelial cell
• Subjective
  • Tumor on head/neck/axilla
• Assessment
  • [Capillary lymphangioma] With thin-walled capillaries
  • [Cavernous lymphangioma] With cavernous vascular space, associated with Turner syndrome

Glomus Tumor / グロムス腫瘍

• Overview
  • Benign neoplasm of smooth muscle cell of glomus body
• Subjective
  • Painful tumor on distal digit (often under fingernails)

Kaposi Sarcoma / Kaposi肉腫

• Overview
  • Borderline neoplasm of endothelial cell, caused by HHV8 infection and immunosuppression (AIDS, transplant, aging)
  • HHV8 infect endothelial cell and stimulate growth
• Subjective
  • Red-purple patches, plaques, nodules: Disease progression
• Objective
  • [PCR] HHV8 (+)
  • [Pathology] Irregular vascular space, plump spindle cells, interspersed erythrocytes and mononuclear cells
• Assessment
  • [Type] Classic KS: In older man, not HIV-related
  • [Type] Endemic African KS: In younger African, not HIV-related
  • [Type] Transplant-associated KS: In organ transplant recipient under immunosuppression
  • [Type] AIDS-associated KS: Most common, AIDS-defining illness
• Plan
  • Surgery, radiotherapy, chemotherapy
  • Withdrawal of immunosuppression: Transplant-associated
  • Antiretroviral therapy: AIDS-associated

Angiosarcoma / 血管肉腫

• Overview
  • Malignant neoplasm of endothelial cell, idiopathic or related to lymphedema after mastectomy, radiation, trauma
• Subjective
  • Initial red papules, later red-tan nodules with blurring margin, bleeding and ulceration: Often in head/neck of elderly
• Objective
  • [Pathology] Irregular vascular space, atypical endothelial cells (various degree of differentiation)
• Plan
  • Surgery, radiotherapy, chemotherapy

Inflammatory Dermatosis / 炎症性皮膚疾患

Urticaria / じんま疹

• Overview
  • Dermal microvascular hyperpermeability due to localized mast cell degranulation of histamine
  • Causes include antigens, exercise, temperature change, stress
• Subjective
  • Pruritic edematous plaques (wheals)
  • Develop and fade within hours, episode for days to months
  • [Angioedema] Edema without pruritus for days, often on eyelid/lip
• Objective
  • [Pathology] Edema and dilated vessels in superficial dermis
• Assessment
  • [Related] Angioedema: Edema of deeper dermis and subcutaneous fat
  • [Related] C1 inhibitor deficiency: Hereditary angioedema due to excessive bradykinin production
• Plan
  • Avoid causative agents
  • Antihistamine

Eczematous Dermatitis / 湿疹性皮膚炎

• Overview
  • Acute inflammation of skin, often due to immune reaction mediated by CD4+ T lymphocytes
  • Causes include external antigen (plant, metal), internal antigen (food, drug), predisposition (atopy)
• Subjective
  • Erythematous pruritic patch/plaque, sometimes with papules/vesicles/crusts/scales: Acute phase
  • Lichenification, pigmentation: Chronic phase
  • [Contact dermatitis] Lesion coincides with contact region
  • [Atopic dermatitis] Recurrent and chronic course, symmetrical distribution
  • [Asteatotic eczema] Dry and itchy skin on extensor surface
  • [Seborrheic dermatitis] Greasy lesions with scales/crusts on seborrheic area
  • [Nummular eczema] Coin-like lesions on lower leg
  • [Autosensitization dermatitis] Widespread pruritic lesions following worsening localized lesion
  • [Stasis dermatitis] Purpura and atrophy on lower leg
  • [Lichen Vidal] Pruritic plaque/lichenification
  • [Pompholyx] Pruritic vesicles at palm/sole
• Objective
  • [Contact dermatitis] Patch test positive
  • [Atopic dermatitis] White dermographism, IgE↑, eosinophil↑
  • [Pathology] Spongiosis (epidermal edema), inflammatory infiltration, acanthosis, hyperkeratosis
• Assessment
  • [Type] Contact dermatitis: Due to contact of causative agents (irritant/allergic)
  • [Type] Atopic dermatitis: Due to atopy and impaired skin barrier function
  • [Type] Asteatotic eczema: Due to decreased sebum secretion and impaired skin barrier function
  • [Type] Seborrheic dermatitis: Due to sebum production and Malassezia colonization
  • [Type] Nummular eczema: Characteristic coin-like lesions
  • [Type] Autosensitization dermatitis: Due to generalized hypersensitivity reaction to worsening localized lesion
  • [Type] Stasis dermatitis: Due to venous stasis of varicose veins
  • [Type] Lichen Vidal: Due to chronic contact irritation
  • [Type] Pompholyx: Characteristic pruritic vesicles on palm/sole
  • [Related] Prurigo: Pruritic acute/chronic papules/nodules
• Plan
  • Topical steroid
  • [Contact dermatitis] Avoid causative agents
  • [Atopic dermatitis] Tacrolimus ointment, JAK inhibitor
  • [Asteatotic eczema] Moisturizer
  • [Seborrheic dermatitis] Antifungals

Erythema Multiforme / 多形紅斑

• Overview
  • Hypersensitivity reaction of skin, due to keratinocyte injury mediated by CD8+ T lymphocytes
  • Causes include infection (herpes, mycoplasma), drug (sulfonamide, carbamazepine), cancer, collagen disease
• Subjective
  • Multiple target-like erythematous macules/patches
• Objective
  • [Pathology] Keratinocyte necrosis, lymphocytic infiltrates along dermoepidermal junction
• Plan
  • Topical steroid, antihistamine

Acute Febrile Neutrophilic Dermatosis / 急性熱性好中球性皮膚症

• Overview
  • Tender erythematous nodule with fever, related to hematologic/solid malignancy (Sweet’s disease)
• Subjective
  • Tender erythematous nodule/plaque: Often on face and upper limbs
  • Often with high fever, arthralgia
• Objective
  • [Blood] Neutrophil↑, CRP↑
  • [Pathology] Neutrophilic infiltration in dermis, edema of dermal papilla
• Plan
  • NSAID, corticosteroid

Pyoderma Gangrenosum / 壊疽性膿皮症

• Overview
  • Noninfectious necrotic ulcer, related to systemic disease (inflammatory bowel disease, hematologic malignancy, rheumatoid arthritis)
• Subjective
  • Necrotic ulcer with violaceous elevated edge
• Objective
  • [Pathology] Neutrophilic infiltration in dermis

Drug Eruption / 薬疹

• Overview
  • Adverse drug reaction of skin, often due to type IV hypersensitivity
• Subjective
  • [Maculopapular] Widespread erythematous papules
  • [Fixed] Erythematous patch at same place due to same drug
  • [SJS] Extensive erythema with blister/erosion on skin/mucosa, fever
  • [TEN] Extensive erythema with necrosis/sloughing of skin/mucosa, fever
  • [DHIS] Extensive erythema, fever, lymphadenopathy
• Objective
  • [Pathology, SJS] Keratinocyte necrosis in cluster
  • [Pathology, TEN] Keratinocyte necrosis in layer
  • [Blood, DHIS] AST/ALT↑, eosinophil↑, anti-HHV6↑
• Assessment
  • [Type] Maculopapular rash: Most common drug eruption
  • [Type] Fixed drug eruption: Same location due to same drug
  • [Type] Stevens-Johnson syndrome: Severe reaction, life-threatening, involve < 10% BSA
  • [Type] Toxic epidermal necrolysis: Severe reaction, high mortality, involve > 10% BSA
  • [Type] Drug-induced hypersensitivity syndrome: Systemic reaction involving organs, due to HHV-6 reactivation
• Plan
  • Terminate causative drug
  • Steroid, antihistamine
  • IVIg, plasma exchange: For severe cases

Graft-Versus-Host Disease / 移植片対宿主病

• Overview
  • Host tissue attacked by graft lymphocyte after bone marrow transplantation
• Subjective
  • [Acute] Edematous erythema, papules,
  • [Chronic] Skin atrophy, sclerosis
• Objective
  • [Pathology, acute] Keratinocyte necrosis. lymphocytic infiltration
  • [Pathology, chronic] Dermal collagen proliferation, bank-like lymphocytic infiltration
• Assessment
  • [Type] Acute GVHD: <100 days
  • [Type] Chronic GVHD: >100 days
• Plan
  • Steroid

Keratosis / 角化症

Psoriasis / 乾癬

• Overview
  • Chronic inflammation of skin with autoimmune basis (environmental + genetic)
  • Result from T cell infiltration, cytokine secretion, keratinocyte proliferation
• Subjective
  • Multiple well-demarcated salmon-colored plaques with silver-white scale: Often on elbow/knee/scalp
  • [Koebner phenomenon] New lesion induced by local trauma: Local inflammation becomes self-perpetuating
  • [Auspitz sign] Pinpoint bleeding when scales scraped off: Thinning of epidermis overlying dermal papillae
  • [Nail change] Pitting, onycholysis
  • [Psoriatic arthritis] Joint pain, deformity: Associated with HLA-B27
• Objective
  • [Pathology] Acanthosis, elongated rete ridges, hyperkeratosis, parakeratosis: Increased keratinocyte turnover rate
  • [Pathology] Neutrophil aggregate in superficial epidermis (spongiform pustule) and stratum corneum (Munro microabscess): Local inflammation
• Assessment
  • [Type] Psoriasis vulgaris (1st common): Erythematous plaques with white scale
  • [Type] Guttate psoriasis: Multiple small drop-shaped lesions
  • [Type] Pustular psoriasis: Localized or generalized lesions with pustules; including palmoplantar pustulosis
  • [Type] Palmoplantar pustulosis: Pustules on palms and soles, related to metal allergy and smoking, associated with sternocostoclavicular hyperostosis
  • [Type] Psoriatic erythroderma: Generalized erythroderma and scaling
• Plan
  • [Topical therapy] Steroid, vitamin D
  • [Light therapy] PUVA, UVB
  • [Biological agents] Anti-TNFα, anti-IL17, anti-IL23

Lichen Planus / 扁平苔癬

• Overview
  • Chronic inflammation of skin
  • May be due to CD8+ T cells response elicited by altered antigen expressed in basal cell
• Subjective
  • Multiple pruritic purple papule/plaque with white lines on skin/mucosa
  • [Wickham striae] White lines in lace-like pattern: Hypergranulosis
  • [Koebner phenomenon] New lesion induced by local trauma: Local inflammation becomes self-perpetuating
• Objective
  • [Pathology] Band-like lymphocytes infiltrate along dermoepidermal junction: Interface dermatitis
  • [Pathology] Basal keratinocyte degeneration and squamatization, dermoepidermal interface sawtoothing: Destruction of basal cells
  • [Pathology] Acanthosis, hypergranulosis, hyperkeratosis: Chronic changes
• Plan
  • Topical steroid

Ichthyosis / 魚鱗癬

• Overview
  • Excessive keratin buildup due to defective desquamation, mostly inherited but also acquired
• Subjective
  • Fish-like scale, dry skin: Often since birth
• Objective
  • [Pathology] Buildup of compacted stratum corneum
• Assessment
  • [Type] Ichthyosis vulgaris: Filaggrin gene mutation lead to impaired water retention
  • [Type] X-linked ichthyosis: Steroid sulfatase deficiency lead to excessive adherence of keratinocytes
  • [Type] Congenital ichthyosiform erythroderma: Erythema without blister
  • [Type] Epidermolytic ichthyosis: Erythema with blister
  • [Type] Lamellar ichthyosis
  • [Related] Palmoplantar keratoderma: Hyperkeratosis of palm/sole
• Plan
  • Moisturizer: For dry skin
  • Salicylic acid: Soften and remove scales

Keratosis Follicularis / 毛包性角化症

• Overview
  • Chronic keratotic papules due to ATP2A2 mutation (Darier’s disease)
• Subjective
  • Keratotic papules in seborrheic/intertriginous part: Onset in adolescence
  • Pruritus, foul smelling: Exacerbated by sweat and sunlight
• Objective
  • [Pathology] Hyperkeratosis, acantholysis
• Assessment
  • [Related] Keratosis pilaris: Noninflammatory keratotic papules on arms/legs, very common
• Plan
  • Retinoid

Blistering Disorder / 水疱性疾患

Pemphigus / 天疱瘡

• Overview
  • Blistering disease due to autoantibody against protein for adherence between keratinocytes (desmoglein)
• Subjective
  • Multiple flaccid bullae with rupture/erosion/erythema in skin/mucosa: Dissolution of epidermis/epithelium
  • [Nikolsky sign] Skin peeling with gentle rubbing
• Objective
  • [Blood] Anti-Dsg3 IgG (+) (vulgaris), anti-Dsg1 IgG (+) (foliaceus)
  • [Pathology] Acantholysis in deep epidermis (suprabasal blister), row of tombstones: In pemphigus vulgaris/vegetans, anti-Dsg3 (deep)
  • [Pathology] Acantholysis in superficial epidermis (subcorneal blister): In pemphigus foliaceus/erythematosus, anti-Dsg1 (superficial)
  • [Pathology] Net-like IgG deposit (all-layer for vulgaris, superficial for foliaceus): Autoantibody against desmoglein (component of desmosome)
• Assessment
  • [Type] Pemphigus vulgaris (1st common): Suprabasal blister, anti-Dsg3
  • [Type] Pemphigus vegetans: Vegetating plaques, anti-Dsg3
  • [Type] Pemphigus foliaceus (2nd common): Subcorneal blister, anti-Dsg1
  • [Type] Pemphigus erythematosus: Lupus-like erythema, anti-Dsg1
  • [Type] Paraneoplastic pemphigus: Often non-Hodgkin lymphoma
• Plan
  • Systemic steroid, immunosuppressant

Bullous Pemphigoid / 水疱性類天疱瘡

• Overview
  • Blistering disease due to autoantibody against protein for adherence of basal keratinocytes to basement membrane (BPAG2)
• Subjective
  • Multiple tense bullae with pruritic erythema in skin/mucosa: Detachment of epidermis and dermis
• Objective
  • [Blood] Anti-BPAG2 IgG (+)
  • [Pathology] Separation of basal keratinocytes and basement membrane (subepidermal blister), lymphocyte and eosinophil infiltrate: Due to anti-BPAG2
  • [Pathology] Linear IgG deposit at dermoepidermal junction: Autoantibody against BPAG2 (component of hemidesmosome)
• Plan
  • Topical steroid
  • Tetracycline

Dermatitis Herpetiformis / 疱疹状皮膚炎

• Overview
  • Blistering disease due to antibody cross-reacting with protein for anchoring of basement membrane to dermis (reticulin)
• Subjective
  • Pruritic grouped vesicles and erythema (urticaria)
• Objective
  • [Pathology] Separation of basement membrane and superficial dermis (subepidermal blister), neutrophil infiltrate at tip of dermal papillae
  • [Pathology] Granular IgA deposit at dermal papillae: Autoantibody against reticulin (anchoring fiber of basement membrane)
• Assessment
  • [Association] Celiac disease: IgA antibody cross-react to reticulin
• Plan
  • Topical steroid
  • Gluten-free diet: If associated with celiac disease

Epidermolysis Bullosa / 表皮水疱症

• Overview
  • Blistering disease due to inherited defect in structural protein of skin
• Subjective
  • Localized (simplex) or generalized (junctional, dystrophic) bullae
• Assessment
  • [Type] Simplex: Blister in basal cell layer, due to mutation of keratin 14/5
  • [Type] Junctional: Blister in lamina lucida, due to mutation of laminin
  • [Type] Dystrophic: Blister beneath lamina densa, due to mutation of COL7A1

Porphyria / ポルフィリン症

• Overview
  • Congenital (or acquired) disturbances of porphyrin metabolism
• Subjective
  • Urticaria and vesicles: Exacerbated by sun exposure
  • Reddish urine: Under sun exposure
• Objective
  • [Pathology] Subepidermal blister, abnormal vessel at superficial dermis
• Assessment
  • [Type] Congenital erythropoietic porphyria
  • [Type] Erythropoietic protoporphyria
  • [Type] Acute intermittent porphyria
  • [Type] Porphyria cutanea tarda

Skin Appendage Disorder / 皮膚付属器疾患

Acne Vulgaris / 尋常性痤瘡

• Overview
  • Inflammation of hair follicle and sebaceous gland
  • Contributed to keratin plug blocking sebum outflow, androgen inducing sebaceous gland hypertrophy, Propionibacterium acnes resulting in proinflammatory fatty acids
• Subjective
  • Erythematous papule/nodule/pustule, with/without central black keratin plug: Open/closed comedones
• Objective
  • [Pathology] Open or closed comedones, immune cell infiltrate
• Plan
  • Antibiotics: For Propionibacterium acnes
  • Vitamin A derivative: Inhibit sebum production

Rosacea / 酒皶

• Overview
  • Chronic inflammation around hair follicle, related to innate immune response
• Subjective
  • Persistent erythema/telangiectasia, papules/pustules, nasal skin thickening (rhinophyma)
• Objective
  • [Pathology] Perifollicular lymphocyte infiltrate, dermal edema/telangiectasia

Miliaria / 汗疹

• Overview
  • Sweat leakage to peripheral tissue due to obstruction of eccrine sweat gland duct
• Subjective
  • Multiple small blisters or papules
• Assessment
  • [Type] Miliaria crystallina: Bullae in corneum
  • [Type] Miliaria rubra: Bullae in epidermis
  • [Type] Miliaria profunda: Bullae in dermis
• Plan
  • Avoid sweating

Alopecia / 脱毛症

• Overview
  • Hair loss
• Subjective
  • [Androgenetic] M-shape receding hairline, vertex hair loss: Chronic progress
  • [Areata] Hair loss in rounded patches: Acute onset
• Assessment
  • [Type] Androgenetic alopecia: Due to androgen (DHT)
  • [Type] Alopecia areata: Related to autoimmune and stress
• Plan
  • 5α-reductase inhibitor
  • Hair transplantation

Panniculitis / 脂肪織炎

Erythema Nodosum / 結節性紅斑

• Overview
  • Inflammation of subcutaneous fat septa, related to delayed hypersensitivity reaction
  • Causes include infection, drug, sarcoidosis, IBD, malignancy
• Subjective
  • Poorly-defined erythematous tender patch/nodule: Often on legs
• Objective
  • [Blood] WBC↑, CRP↑
  • [Pathology] Edema/fibrin/infiltration of subcutaneous fat septa

Erythema Induratum / 硬結性紅斑

• Overview
  • Inflammation of subcutaneous fat lobule, related to vasculitis or tuberculosis
  • Vasculitis of deep vessels supplying subcutaneous fat leads to fat necrosis
• Subjective
  • Erythematous slightly-tender nodule, ulceration: Often on legs
• Objective
  • [Pathology] Caseating granulomatous inflammation of subcutaneous fat lobule

Infectious Disorder / 感染症

Herpes Simplex / 単純疱疹

• Overview
  • Viral infection caused by herpes simplex virus (HSV1/2), primary or latent infection
  • Latent infection in trigeminal ganglion (HSV1) or sacral ganglion (HSV2), reactivated in immunocompromised state (stress)
• Subjective
  • [Labial] Painful vesicles on lips and perioral region
  • [Genital] Painful vesicles on external genitalia, symmetric ulceration
• Assessment
  • [Variant] Herpetic gingivostomatitis: Oral mucosa involvement in children
  • [Variant] Kaposi’s varicella form eruption: Widespread involvement in patient with weakened skin barrier (atopic dermatitis)
  • [Variant] Herpetic whitlow: Finger involvement in infant
• Objective
  • [Pathology] Intraepithelial vesicles
  • [Cytology] Giant cell, inclusion body
• Plan
  • Acyclovir and derivatives

Herpes Zoster / 帯状疱疹

• Overview
  • Viral infection caused by varicella-zoster virus (VZV), latent infection (primary: varicella)
  • Latent infection in dorsal root ganglia, reactivated in immunocompromised state (aging, stress, malignancy, HIV, steroid)
• Subjective
  • Vesicles with erythema along dermatome (unilateral, band-like)
  • Neuropathic pain: May be persistent
• Assessment
  • [Variant] Ramsay Hunt syndrome: Facial palsy due to involvement of CN VII geniculate ganglion
  • [Related] Pityriasis rosea: Multiple erythema with scales due to HHV6/7 reactivation
• Plan
  • Acyclovir and derivatives
  • NSAID: For acute pain
  • Pregabalin: For post-herpetic neuralgia

Verruca / 疣贅

• Overview
  • Viral infection caused by human papillomavirus (HPV), transmitted by direct contact
  • HPV 16/18 are carcinogenic due to E6 inhibiting p53
• Subjective
  • [Verruca vulgaris] Tan papules/nodules on various location
  • [Verruca plana] Slightly elevated papules on face/dorsal-hand
  • [Verruca plantaris] Ant-hill-like nodules on soles/palms
  • [Condyloma acuminata] Cauliflower-like mass on genitalia/anus
• Objective
  • [Pathology] Papillomatous epidermal hyperplasia, cytoplasmic vacuolization (koilocytosis)
• Assessment
  • [Type] Verruca vulgaris: HPV 2/27/57
  • [Type] Verruca plana: HPV 3/10
  • [Type] Condyloma acuminatum: HPV 6/11
• Plan
  • [Verruca vulgaris] Topical salicylic acid, cryotherapy,
  • [Condyloma acuminatum] Topical imiquimod, cryotherapy

Molluscum Contagiosum / 伝染性軟属腫

• Overview
  • Viral infection caused by a poxvirus, transmitted by direct contact
• Subjective
  • Multiple skin-colored umbilicated papules, curd-like material from central umbilication
• Objective
  • [Pathology] Cup-like epidermal hyperplasia, molluscum body (large cytoplasmic inclusion) in stratum granulosum/corneum

Folliculitis / 毛包炎

• Overview
  • Bacterial infection of hair follicle caused by staphylococcus aureus
• Subjective
  • Erythema, swelling, pustule: Around hair follicle
• Assessment
  • [Type] Folliculitis: Superficial infection of single follicle
  • [Type] Furuncle: Deep infection of single follicle
  • [Type] Carbuncle: Deep infection of multiple follicle
  • [Related] Paronychia: Infection of skin around nail
• Plan
  • Antibiotics

Impetigo / 膿痂疹

• Overview
  • Bacterial infection of epidermis caused by staphylococcus/streptococcus, highly contagious
  • Local invasion result in serous exudate (crust)
  • Exfoliative toxin cleave desmoglein1 (blister)
• Subjective
  • Erythematous macule/patch with honey-colored crust (contagiosa) or blister/erosion (bullosa)
• Objective
  • [Pathology] Neutrophil accumulation beneath stratum corneum
• Assessment
  • [Type] Impetigo contagiosa: Caused by group A streptococcus (also staphylococcus now)
  • [Type] Impetigo bullosa: Caused by staphylococcus aureus
• Plan
  • Antibiotics

Cellulitis / 蜂巣炎

• Overview
  • Bacterial infection of dermis and subcutaneous tissue caused by staphylococcus/streptococcus
• Subjective
  • Ill-defined painful edematous erythema: Rapidly enlarging
  • Fever, chill
• Objective
  • [Blood] WBC↑, CRP↑
• Assessment
  • [Related] Erysipelas: Infection of dermis caused by group A streptococcus
• Plan
  • Antibiotics
  • Drainage

Necrotizing Fasciitis / 壊死性筋膜炎

• Overview
  • Bacterial infection of subcutaneous tissue and fascia caused by streptococcus/staphylococcus
• Subjective
  • Ill-defined painful edematous erythema/purpura/blister/sloughing: Rapidly progress
  • Fever, septic shock, multiorgan failure
• Objective
  • [Blood] WBC↑, CRP↑
  • [CT] Subcutaneous edema
• Assessment
  • [Related] Gas gangrene: Muscle necrosis with gas production caused by clostridium perfringens
• Plan
  • Emergent debridement
  • Antibiotics

Tinea / 白癬

• Overview
  • Superficial fungal infection caused by dermatophytes (mainly Trichophyton)
• Assessment
  • [Type] Tinea capitis: Scalp, erythematous patch with hair loss
  • [Type] Tinea corporis: Various location, expanding round erythematous patch
  • [Type] Tinea cruris: Inguinal area, erythematous patch with scaly border
  • [Type] Tinea pedis: Sole, diffuse erythema and scaling (interdigital, vesicular, hyperkeratotic)
  • [Type] Tinea unguium: Nail, discoloration and thickening/deformity
  • [Related] Tinea versicolor: Trunk, discolored macule or patch, caused by malassezia instead of dermatophyte
  • [Related] Sporotrichosis: Deep fungal infection caused by sporothrix
• Objective
  • [KOH] Septate hyphae
  • [Pathology] Red hyphae in stratum corneum under PAS stain
• Plan
  • Topical azoles/allylamines

Scabies / 疥癬

• Overview
  • Itchy skin rash caused by Sarcoptes scabiei parasitizing corneum layer, transmitted by direct or indirect contact
• Subjective
  • Extremely pruritic red papules
  • Track-like burrows (scabies burrow)
• Plan
  • Topical phenothrin, oral ivermectin
  • Environmental cleaning

Miscellaneous Skin Disorder / その他の皮膚疾患

Hypertrophic Scar & Keloid / 肥厚性瘢痕・ケロイド

• Overview
  • Excessive collagen production due to abnormal wound healing
• Subjective
  • Skin elevation at wound site
• Assessment
  • [Type] Hypertrophic scar: Stay within original boundary
  • [Type] Keloid: Extend beyond original boundary
• Plan
  • Steroid injection
  • Surgical excision

Clavus & Callus / 鶏眼・胼胝

• Overview
  • Noninflammatory keratosis due to chronic physical irritation
• Subjective
  • [Clavus] Skin hardening with tenderness
  • [Callus] Skin thickening without tenderness
• Assessment
  • [Type] Clavus: Inward growth
  • [Type] Callus: Outward growth
• Plan
  • Salicylic acid, excision

Pressure Ulcer / 褥瘡

• Overview
  • Skin damage due to long-term pressure causing skin hypoperfusion
• Subjective
  • Skin defect, erythema: Common in sacral area
  • Black necrosis, yellow necrosis, red granulation, white scarring: Disease progress
• Assessment
  • [Stage] Stage I: Erythema
  • [Stage] Stage II: Blister
  • [Stage] Stage III: Fat
  • [Stage] Stage IV: Bone
• Plan
  • Wet dressing, negative pressure
  • Pressure redistribution: Preventive

Burn / 熱傷

• Overview
  • Skin damage due to high temperature
• Subjective
  • Erythema, edema: 1st-degree
  • Blister, erosion: 2nd-degree
  • White plaque, sensation loss: 3rd-degree
  • Shock, sepsis: Impaired skin barrier
• Assessment
  • [Stage] First-degree burn: To epidermis
  • [Stage] Second-degree burn: To dermis
  • [Stage] Third-degree burn: To subcutaneous tissue
  • [Evaluation] Rule of 9s
• Plan
  • Topical steroid: For 1st-degree burn
  • Vaseline ointment: For 2nd-degree burn
  • Debridement, skin grafting: For 3rd-degree burn
  • IV fluid (parkland formula), antibiotics: For systemic disease
  • Intubation: If airway burn

Solar Dermatitis / 日光皮膚炎

• Overview
  • Skin damage due to excessive sun exposure (UVB)
• Subjective
  • Erythema, edema, blister: Sunburn
  • Pigmentation: Suntan
• Assessment
  • [Related] Photosensitive disorder: Chromophore in skin activated by sun and leading to toxic or allergic reaction
• Plan
  • Sunscreen: Preventive

Xeroderma Pigmentosum / 色素性乾皮症

• Overview
  • Hereditary disorder of photosensitivity due to defective DNA repair (nucleotide excision repair)
• Subjective
  • Severe sunburn, diffuse pigmentation, multiple skin malignancy
  • Gait disturbance, hearing loss
• Plan
  • UV protection

Orthopedic Surgery / 整形外科

Urology / 泌尿器科

Gynecology / 婦人科

Vulva Disorder / 外陰疾患

Bartholin Cyst / Bartholin腺嚢胞

• Overview
  • Infection of Bartholin gland due to obstruction of duct
• Subjective
  • Cyst, pain
• Plan
  • Excision, marsupialization

Lichen Sclerosus / 硬化性苔癬

• Overview
  • Chronic skin lesion, related to autoimmune
• Subjective
  • Smooth white patch/plaque, mostly on genitalia
• Objective
  • [Pathology] Thinning of epidermis, sclerosis of superficial dermis, bandlike lymphocyte infiltrate in dermis

Lichen Simplex Chronicus / 慢性単純性苔癬

• Overview
  • Chronic skin lesion, related to rubbing/scratching (squamous cell hyperplasia)
• Subjective
  • Thickened scaly plaque
• Objective
  • [Pathology] Acanthosis, hyperkeratosis

Vulvar Intraepithelial Neoplasia & Carcinoma / 外陰上皮内腫瘍・癌

• Overview
  • Premalignant and malignant neoplasm of vulvar epithelium, related or unrelated to high-risk HPV (16/18)
• Subjective
  • Gray-while papule/plaque: Vulvar intraepithelial neoplasia
  • Exophytic or ulcerated lesion: Vulvar carcinoma
• Objective
  • [Pathology] Immature basaloid cells within epidermis: Classic vulvar intraepithelial neoplasia
  • [Pathology] Immature basaloid cells invading dermis: Basaloid carcinoma
  • [Pathology] Atypical but mature basal/squamous cells within epidermis: Differentiated vulvar intraepithelial neoplasia
  • [Pathology] Atypical but mature keratinizing squamous cells invading dermis: Keratinizing squamous cell carcinoma
• Assessment
  • [Type, HPV] Classic vulvar intraepithelial neoplasia: Due to HPV infection
  • [Type, HPV] Basaloid and warty carcinoma: From classic VIN, younger age
  • [Type, non-HPV] Differentiated vulvar intraepithelial neoplasia: Due to long-standing lichen sclerosus or lichen simplex chronicus
  • [Type, non-HPV] Keratinizing squamous cell carcinoma: From differentiated VIN, older age
• Plan
  • Excision, vulvectomy

Papillary Hidradenoma / 乳頭状汗腺腫

• Overview
  • Benign neoplasm of modified apocrine sweat gland
• Subjective
  • Subcutaneous nodules on labia majora or interlabial fold
• Objective
  • [Pathology] Papillary projections, columnar secretary cells and myoepithelial cells

Extramammary Paget Disease / 乳房外Paget病

• Overview
  • Malignant neoplasm of modified apocrine sweat gland within epidermis
• Subjective
  • Pruritic red patch on labia majora
• Objective
  • [Pathology] Large cells with pale cytoplasm (mucopolysaccharide), cytokeratin 7 (+)
• Plan
  • Wide excision

Vagina Disorder / 腟疾患

Vaginal Adenosis / 腟腺症

• Overview
  • Residual glandular epithelium in vagina, related to DES exposure in utero
• Objective
  • [Pathology] Columnar mutinous epithelium
• Assessment
  • [Association] Clear cell carcinoma

Gartner Duct Cyst / Gartner管嚢胞

• Overview
  • Benign cyst from residual Wolffian duct
• Subjective
  • Fluid-filled submucosal cysts in vagina lateral wall
• Assessment
  • [Related] Müllerian cyst: Mucus cyst from müllerian duct

Vaginal Intraepithelial Neoplasia & Carcinoma / 膣上皮内腫瘍・癌

• Overview
  • Premalignant or malignant neoplasm of vagina, due to high-risk HPV (16/18) infection
• Subjective
  • Vaginal bleeding

Embryonal Rhabdomyosarcoma / 胎児型横紋筋肉腫

• Overview
  • Malignant neoplasm of embryonal rhabdomyoblast (sarcoma botryoides)
• Subjective
  • Polypoid grapelike mass in vagina of infants/children
• Objective
  • [Pathology] Small round to spindle cells, crowded (superficial) or in edematous stroma (deep)
• Plan
  • Surgery + chemotherapy

Cervix Disorder / 子宮頸疾患

Cervicitis / 子宮頸管炎

• Overview
  • Acute or chronic inflammation of cervix, due to vaginal environment change (reduced lactobacilli) or infection
  • Environment change: Bleeding, sexual intercourse, vaginal douching, antibiotics
  • Infection: Gonococci, chlamydiae, HSV
• Assessment
  • [Type] Acute cervicitis
  • [Type] Chronic cervicitis

Endocervical Polyp / 子宮頸管ポリープ

• Overview
  • Benign exophytic growth in endocervical canal
• Subjective
  • Sessile or polypoid mass in endocervical canal
• Objective
  • [Pathology] Fibrous stroma covered by mucus-secreting glands
• Plan
  • Curettage

Cervical Intraepithelial Neoplasia & Carcinoma / 子宮頸部上皮内腫瘍・癌

• Overview
  • Premalignant and malignant neoplasm of cervical epithelium, due to high risk HPV (16/18) infection
  • HPV Infect immature squamous cells at squamocolumnar junction
  • HPV replicate in mature squamous cell and establish persistent infection
  • E6 inactivate p53 and and E7 inactivates RB
  • Viral DNA integrates into host cell genome
• Subjective
  • Abnormal vaginal bleeding
• Objective
  • [Pap smear] Enlarged nuclei (N/C ratio↑), koilocytosis, HPV-DNA (+)
  • [Colposcopy] Aceto-white area
  • [Pathology] Nuclear atypia (enlargement, hyperchromasia, pleomorphism), koilocytic atypia (perinuclear halo)
  • [Pathology] HPV-DNA (upper), Ki-67 (basal>upper), p16 (whole)
  • [Pathology, LSIL] Nuclear atypia in lower 1/3 epithelium
  • [Pathology, HSIL] Nuclear atypia in lower 2/3 to full epithelium
  • [Pathology, squamous] Nests of malignant squamous cells invading stroma
  • [Pathology, adeno] Glandular epithelium with large hyperchromatic nuclei invading stroma
• Assessment
  • [Type] LSIL (CIN I): 60% regress, 30% persist, 10% to HSIL
  • [Type] HSIL (CIN II/III): 30% regress, 60% persist, 10% to carcinoma
  • [Type] Squamous cell carcinoma: 80%
  • [Type] Adenocarcinoma: 15%
  • [Type] Adenosquamous carcinoma: <5%
  • [Type] Neuroendocrine carcinoma: <5%
  • [Stage] Stage 0: Carcinoma in situ
  • [Stage] Stage I: Carcinoma confined to cervix
  • [Stage] Stage II: Carcinoma beyond cervix
  • [Stage] Stage III: Carcinoma to lower 1/3 vagina or pelvic wall
  • [Stage] Stage IV: Carcinoma to bladder/rectum mucosa, beyond true pelvis, metastasis
• Plan
  • Observation: LSIL
  • Conization: HSIL
  • Hysterectomy, lymph node dissection: Cancer
  • Radiotherapy, chemotherapy: Advanced
  • [Prevention] HPV vaccine

Uterus Disorder / 子宮疾患

Uterine Anomaly / 子宮奇形

• Overview
  • Abnormal uterus development from Mullerian duct
• Subjective
  • Infertility, recurrent pregnancy loss
  • Menstrual molimen
• Objective
  • [Hysterosalpingography] Uterine anomaly
• Assessment
  • [Type] Unicornuate uterus
  • [Type] Double uterus
  • [Type] Bicornuate uterus
  • [Type] Septate uterus
  • [Type] Arcuate uterus
  • [Type] Imperforate hymen
• Plan
  • Hysteroplasty

Dysfunctional Uterine Bleeding / 機能性子宮出血

• Overview
  • Abnormal/absent uterine bleeding due to hormonal disturbances
  • [DUB] Causes include puberty, perimenopausal, weight loss, stress, hyperprolactinemia, PCOS
  • [Amenorrhea] Causes include anorexia nervosa, Sheehan syndrome, premature ovarian failure, Turner syndrome
• Subjective
  • Polymenorrhea, oligomenorrhea, menorrhagia, hypomenorrhea
  • Amenorrhea
  • Infertility
• Objective
  • [Pathology] Stromal condensation without secretory changes (subnuclear vacuoles, predecidual changes)
• Assessment
  • [Condition] Anovulatory cycle: Failure of ovulation causes excessive estrogen stimulation unopposed by progesterone
  • [Condition] Luteal insufficiency: Shortened luteal phase due to insufficient secretion of progesterone
  • [Condition] Amenorrhea: Absent estrogen/progesterone stimulation due to hypothalamus/pituitary/ovary lesion
• Plan
  • Progestogen, estrogen-progestogen: For bleeding
  • Clomiphene, gonadotropin: For infertility

Endometritis / 子宮内膜炎

• Overview
  • Acute or chronic inflammation of endometrium
• Subjective
  • Pelvic pain, abnormal bleeding
• Assessment
  • [Type] Acute endometritis: Due to retained conception products after delivery/miscarriage
  • [Type] Chronic endometritis: Due to chronic PID, retained gestational tissue, intrauterine contraceptive devices, tuberculosis
• Plan
  • Curettage
  • Antibiotics

Endometriosis / 子宮内膜症

• Overview
  • Ectopic endometrial tissue outside of uterus, theories include regurgitation, metastasis, metaplasia, stem cell
  • Common sites: Douglas pouch, ovary, peritoneum
  • Additional alteration: Release of proinflammatory and angiogenic factors, increased estrogen and retinoic acid production, mutation in tumor suppressor genes and oncogenes
• Subjective
  • Dysmenorrhea, dyspareunia, pelvic pain: In reproductive female
  • Infertility: Due to adhesion
  • [Adenomyosis] Menometrorrhagia
• Objective
  • [Pelvic exam] Retroverted uterus, restricted mobility
  • [Ultrasound, MRI] Ovarian cyst, myometrium thickening (adenomyosis)
  • [Laparoscopy] Red/black/white peritoneum lesion
  • [Blood] CA125↑
  • [Pathology, gross] Bleeding, fibrous adhesions, chocolate cyst
  • [Pathology, micro] Endometrial gland and stroma, atypical features (cytologic atypia, glandular crowding)
• Assessment
  • [Related] Adenomyosis: Endometrial tissue in myometrium
  • [Association] Ovarian cancer (endometriosis, clear cell)
• Plan
  • Hormone: LEP, progestin, GNRH agonist, danazol
  • Surgery: Ablation, excision, adhesiolysis, hysterectomy

Endometrial Polyp / 子宮内膜ポリープ

• Overview
  • Benign exophytic growth of endometrium, responsive to estrogen (related to tamoxifen)
• Subjective
  • Sessile or polypoid mass

Endometrial Hyperplasia / 子宮内膜増殖症

• Overview
  • Benign or premalignant proliferation of endometrial gland, due to prolonged estrogen stimulation of endometrium
  • Causes: Prolonged estrogen administration, obesity, PCOS, granulosa cell tumor
  • Often with PTEN inactivating mutation (same as endometrial carcinoma)
• Subjective
  • Abnormal vaginal bleeding
• Objective
  • [Ultrasound] Endometrium thickening
  • [Pathology] Increased gland-to-stroma ratio, retained intervening stroma: Typical hyperplasia
  • [Pathology] Nuclear atypia (vesicular nuclei, prominent nucleoli), back-to-back gland crowding: Atypical hyperplasia
• Assessment
  • [Type] Typical hyperplasia: Rarely progress to carcinoma
  • [Type] Atypical hyperplasia: Often progress to carcinoma
• Plan
  • Observation: Typical hyperplasia
  • Hysterectomy: Atypical hyperplasia
  • Curettage + progestin: Atypical hyperplasia but desire birth

Endometrial Carcinoma / 子宮内膜癌

• Overview
  • Malignant neoplasm of endometrial gland
  • Type I: Due to unopposed estrogen (obesity, nulliparity, PCOS), mutations include PTEN, PIK3CA, KRAS, ARID1A, also MSI, POLE, TP53
  • Type II: Due to endometrial atrophy, mutations include TP53, also chromosomal instability
  • MMMT: Due to sarcomatous transformation, mutations include PTEN, TP53, PIK3CA,
• Subjective
  • Abnormal vaginal bleeding: Irregular, postmenopausal
  • Hypogastric pain
• Objective
  • [Hysteroscopy] Exophytic mass, atypical vessels
  • [Ultrasound] Endometrium thickening
  • [MRI] Junctional zone defect
  • [Pathology, endometrioid] Well-formed glands, solid sheets: Well-differentiated (gland only), moderately-differentiated (solid <50%), poorly differentiated (solid >50%)
  • [Pathology, serous] Papillary growth, cytologic atypia
  • [Pathology, carcinosarcoma] Mixed epithelial and stromal components (metastasis only epithelial)
• Assessment
  • [Type] Type I (endometrioid): More, younger, better prognosis
  • [Type] Type II (serous): Less, older, poorer prognosis
  • [Type] MMMT (carcinosarcoma): Least, similar to type II
  • [Grade] Grade 1~3: Endometrioid
  • [Grade] Grade 3: Serous
  • [Stage] Stage I: Carcinoma confined to corpus uteri
  • [Stage] Stage II: Carcinoma to cervix
  • [Stage] Stage III: Carcinoma to outside of uterus
  • [Stage] Stage IV: Carcinoma to bladder/rectum mucosa, beyond true pelvis, metastasis
• Plan
  • Hysterectomy
  • Adjuvant radiotherapy/chemotherapy

Adenosarcoma / 腺肉腫

• Overview
  • Neoplasm with malignant endometrial stroma and benign endometrial gland
• Objective
  • [Pathology] Biphasic pattern of malignant stroma and benign glands

Stromal Tumor / 間質性腫瘍

• Overview
  • Benign or malignant neoplasm of endometrial stroma, often due to translocation including JAZF1-SUZ12, YWHAE-NUTM2A/B
• Assessment
  • [Type] Stromal nodule: Benign
  • [Type] Low-grade stromal sarcoma: JAZF1-SUZ12 fusion
  • [Type] High-grade stromal sarcoma: YWHAE-NUTM2A/B fusion

Leiomyoma / 子宮筋腫

• Overview
  • Benign neoplasm of smooth muscle cell, related to estrogen, alteration include HMGIC/HMGIY rearrangement and MED12 mutation
• Subjective
  • Abnormal vaginal bleeding, menorrhagia, dysmenorrhea
  • Hypogastric pain, low back pain, frequent urination
  • Infertility, increased spontaneous abortion
• Objective
  • [Echo, MRI, hysteroscopy] Solid pelvic mass
  • [Pathology] Circumscribed round firm gray-white tumors: At intramural, submucosal, subserosal
  • [Pathology] Uniform spindle cell, low mitotic index
• Assessment
  • Malignant transformation is extremely rare
• Plan
  • Observation
  • GnRH agonist
  • Myomectomy, hysterectomy

Leiomyosarcoma / 平滑筋肉腫

• Overview
  • Malignant neoplasm of smooth muscle cell, alteration include complex karyotype and MED12 mutation
• Objective
  • [Pathology] Nuclear atypia, mitotic index
• Plan
  • Hysterectomy

Fallopian Tube Disorder / 卵管疾患

Salpingitis / 卵管炎

• Overview
  • Inflammation of Fallopian tube
• Assessment
  • [Type] Suppurative salpingitis: Gonococcus or Chlamydiae infection
  • [Type] Tuberculous salpingitis: Mycobacterium infection

Paratubal Cyst / 傍卵管嚢腫

• Overview
  • Benign fluid-filled cyst adjacent to fallopian tube, remnant of mullerian duct
• Objective
  • [Pathology] Cyst lined by benign serous epithelium

Fallopian Tube Carcinoma / 卵管癌

• Overview
  • Malignant neoplasm of fallopian tube epithelium
  • May be origin of serous ovarian cancer

Ovary Disorder / 卵巣疾患

Functional Cyst / 機能性嚢胞

• Overview
  • Unruptured follicles (or ruptured and immediately sealed)
• Objective
  • [Ultrasound] Hypoechoic cyst
  • [Pathology] Fluid-filled cyst lined by granulosa cell
• Assessment
  • [Type] Follicle cyst: Spontaneous regress
  • [Type] Luteal cyst: Often in pregnancy

Epithelial Tumor / 上皮性腫瘍

• Overview
  • Neoplasm from mullerian epithelial cell (ovarian/tubal epithelium, endometriosis)
  • [Serous] Related to nulliparity (increased ovulation) and BRCA1/2 germline mutation, derived from benign/borderline tumor (low-grade, KRAS/BRAF mutation) or inclusion cyst of fallopian epithelium (high-grade or BRCA-related, TP53 mutation, genomic imbalance)
  • [Mucinous] KRAS mutation
  • [Endometrioid] Related to endometriosis, similar to endometrial cancer (PTEN/PIK3CA/ARID1A/KRAS mutation)
  • [Clear cell] Related to endometrioisis, similar to endometrial cancer (PTEN/PIK3CA/ARID1A/KRAS mutation)
• Subjective
  • Abdominal distention or pain
  • Urinary symptoms, gastrointestinal symptoms: Tumor compression
  • Ascites: Peritoneal seeding
• Objective
  • [Blood] CA125↑ (serous, endometrioid, clear cell), CEA↑ (mucinous), CA19-9↑ (mucinous)
  • [Ultrasound] Unilocular (serous) or multilocular (mucinous) cyst, irregular wall thickening, papillary solid component
  • [Pathology, Serous] Columnar epithelium (benign), increased complexity (borderline), micropapillary (low-grade), nuclear atypia and stromal invasion (high-grade)
  • [Pathology, Mucinous] Columnar epithelium with mucin (benign), increased complexity (borderline), confluent glandular growth (malignant)
  • [Pathology, Endometrioid] Endometrium-like tubular gland
  • [Pathology, Clear cell] Gestational endometrium-like clear cell, hobnail cell
  • [Pathology, Transitional cell] Urothelium-like nests, ovarian stroma
• Assessment
  • [Type] Serous: Benign (60%, cystadenoma/cystadenofibroma), borderline, malignant (low-grade/high-grade), often bilateral
  • [Type] Mucinous: Benign (80%) (cystadenoma/cystadenofibroma), borderline, malignant
  • [Type] Endometrioid: Benign, borderline, malignant (mostly)
  • [Type] Clear cell: Benign, borderline, malignant (mostly)
  • [Type] Transitional cell (Brenner): Benign (mostly), borderline, malignant
  • [Stage] Stage I: Carcinoma confined to ovary
  • [Stage] Stage II: Carcinoma to pelvic organ
  • [Stage] Stage III: Carcinoma to retroperitoneal lymph node or extrapelvic peritoneum
  • [Stage] Stage IV: Metastasis
• Plan
  • Cystectomy: For benign tumor
  • Unilateral salpingo-oophorectomy: For early malignant tumor
  • Bilateral salpingo-oophorectomy + hysterectomy + omentectomy: For malignant tumor (staging and debulking)
  • Neoadjuvant chemotherapy + debulking surgery + adjuvant chemotherapy (paclitaxel + carboplatin): For advanced malignant tumor
  • Prophylactic salpingo-oophorectomy: For germline BRCA1/2 mutation

Sex Cord-Stromal Tumor / 性索間質性腫瘍

• Overview
  • Neoplasm from stromal cell (derived from sex cord)
  • [Granulosa cell tumor] Granulosa cell differentiation, FOXL2 mutation
  • [Sertoli-Leydig cell tumor] Sertoli or Leydig cell differentiation, DICER1 mutation
  • [Fibroma/Thecoma] Stromal fibroblast or theca cell differentiation
• Subjective
  • Abnormal genital bleeding (endometrial hyperplasia/carcinoma), proliferative breast disease: Granulosa cell tumor (adult)
  • Precocious puberty: Granulosa cell tumor (juvenile)
  • Amenorrhea, breast atrophy, hirsutism, clitoris hypertrophy, voice deepening: Sertoli-Leydig cell tumor
  • Pelvic mass/pain, ascites, hydrothorax: Fibroma/Thecoma (Meigs syndrome)
• Objective
  • [Blood] Estrogen↑ (granulosa), androgen↑ (Sertoli-Leydig), inhibin↑ (both)
  • [Ultrasound] Solid tumor
  • [Pathology, Granulosa cell tumor] Small cuboidal/polygonal cells in cords/sheets, follicle-like structure (Call-Exner body)
  • [Pathology, Sertoli-Leydig cell tumor] Tubules composed of Sertoli/Leydig cells
  • [Pathology, Fibroma/Thecoma] Well-differentiated fibroblast, scant collagenous stroma
• Assessment
  • [Type] Granulosa cell tumor: Malignant (low-grade)
  • [Type] Sertoli-Leydig cell tumor: Malignant (low-grade)
  • [Type] Fibroma/Thecoma: Benign
• Plan
  • Unilateral salpingo-oophorectomy
  • Bilateral salpingo-oophorectomy + hysterectomy + omentectomy

Germ Cell Tumor / 胚細胞腫瘍

• Overview
  • Neoplasm from germ cell
  • [Teratoma] Embryonic differentiation
  • [Yolk sac tumor] Extraembryonic differentiation
  • [Choriocarcinoma] Extraembryonic differentiation
  • [Dysgerminoma] No specific differentiation, KIT mutation
• Subjective
  • Abdominal mass/pain
  • Acute pelvic pain: Ovarian torsion (often in teratoma)
• Objective
  • [Blood] AFP↑ (yolk sac tumor), hCG↑ (choriocarcinoma), LDH↑ (dysgerminoma)
  • [Ultrasound, CT, MRI] Heterogenous cyst (hair ball, fat, tooth) (teratoma), solid tumor
  • [Pathology, Mature teratoma] Ectoderm (squamous epithelium, hair follicles, sebaceous gland, neural tissue), mesoderm (fat, bone, cartilage, thyroid)
  • [Pathology, Monodermal teratoma] Mature thyroid tissue (struma ovarii)
  • [Pathology, Immature teratoma] Immature neuroepithelium, ectoderm, mesoderm
  • [Pathology, Yolk sac tumor] Central vessel enveloped by tumor cells (Schiller-Duval body)
  • [Pathology, Choriocarcinoma] Proliferating syncytiotrophoblast and cytotrophoblast
  • [Pathology, Dysgerminoma] Nests of large cells with clear cytoplasm, in fibrous stroma with lymphocyte infiltration
• Assessment
  • [Type] Mature teratoma (dermoid cyst): Benign (rarely transform to SCC), associated with inflammatory limbic encephalitis
  • [Type] Monodermal teratoma: Benign (struma ovarii, carcinoid)
  • [Type] Immature teratoma: Malignant
  • [Type] Yolk sac tumor: Malignant
  • [Type] Choriocarcinoma: Malignant
  • [Type] Dysgerminoma: Malignant (counterpart of testicular seminoma), associated with pseudohermaphroditism
• Plan
  • Cystectomy: For teratoma
  • Unilateral salpingo-oophorectomy + adjuvant chemotherapy (bleomycin + etoposide + cisplatin): For malignant tumor

Metastatic Tumor / 転移性腫瘍

• Overview
  • From uterus, fallopian tube, contralateral ovary, breast, colon, stomach, often bilateral
• Objective
  • [Pathology] Mucin-producing signet ring cell (Krukenberg tumor): Often from signet ring gastric cancer

Polycystic Ovarian Syndrome / 多囊胞性卵巣症候群

• Overview
  • Endocrine disorder related to excessive androgen production and metabolic disorder
• Subjective
  • Menstrual abnormality, chronic anovulation, infertility: Endocrine disturbance
  • Hirsutism, acne, voice deepening: Hyperandrogenism
  • Obesity, diabetes mellitus, premature atherosclerosis: Metabolic disorder
• Objective
  • [Blood] LH↑, FSH→, androgen↑, estrogen↑
  • [Ultrasound] Polycystic ovary
• Assessment
  • [Related] Stromal hyperthecosis: Proliferated and luteinized stromal cells, similar symptoms with PCOS
• Plan
  • Weight loss
  • Progestogen, estrogen-progestogen: For menstrual abnormality
  • Clomiphene, gonadotropin, ovarian drilling: For infertility

Premature Ovarian Failure / 早発卵巣不全

• Overview
  • Premature loss of ovarian function before 40
• Subjective
  • Amenorrhea, infertility
  • [Climacteric] Menstrual irregularity, hot flash, flushing, sweating, depression, irritability, insomnia, joint stiffness
• Objective
  • [Blood] Estrogen↓, GnRH↑
• Assessment
  • [Related] Climacteric disturbance: Functional disorders during menopausal period
• Plan
  • Hormone replacement therapy

Ovarian Hyperstimulation Syndrome / 卵巣過剰刺激症候群

• Overview
  • Ovulation induction therapy (particularly hMG-hCG) lead to multiple follicle ovulation and increased vascular permeability, often in PCOS patients
• Subjective
  • Abdominal distension, nausea/vomiting: Ascites
  • Dyspnea: Pleural effusion
  • Oliguria: Hemoconcentration
• Objective
  • [Ultrasound] Ovary enlargement with multiple cysts, ascites, pleural effusion
  • [Blood] Hemoconcentration, hypoproteinemia
• Plan
  • IV fluid, albumin
  • Dopamine

Sexually Transmitted Infection / 性感染症

Genital Herpes / 性器ヘルペス

• Overview
  • Infection of external genitalia caused by HSV2/1 with primary and latent infection
  • Latent in lumbosacral nerve ganglia, reactivate under decreased immune function
• Subjective
  • External genitalia pain/vesicles/ulcer (kissing ulcer)
  • Fever, lymphadenopathy
• Objective
  • [Cytology] Multinucleated giant cell, intranuclear inclusion body
  • [Smear] Culture (+), antigen (+), PCR (+)
• Plan
  • Valacyclovir, acyclovir

Condyloma Acuminatum / 尖圭コンジローマ

• Overview
  • Infection of external genitalia caused by HPV6/11
• Subjective
  • Painless exophytic warts on vulvar/perineal/perianal region (less often vagina/cervix)
• Objective
  • [Smear] PCR (+)
  • [Pathology] Papillary exophytic growth, koilocytic atypia (nuclear enlargement, perinuclear halo)
• Plan
  • Topical imiquimod, cryotherapy
  • [Prevention] HPV vaccine

Chlamydial Infection / クラミジア感染症

• Overview
  • Infection of lower/upper genital tract caused by Chlamydia trachomatis
• Subjective
  • Asymptomatic
  • Serous vaginal discharge, abnormal bleeding: Cervicitis
  • Infertility, ectopic pregnancy: Pelvic inflammatory disease
• Objective
  • [Smear] PCR (+)
• Plan
  • Macrolide, fluoroquinolone, tetracycline

Gonococcal Infection / 淋菌感染症

• Overview
  • Infection of lower/upper genital tract caused by Neisseria gonorrhoeae
• Subjective
  • Purulent vaginal discharge, abnormal bleeding: Cervicitis
  • Dysuria, urethral discharge: Urethritis
  • Pelvic pain, adnexal tenderness, fever: Pelvic inflammatory disease
  • Infertility, ectopic pregnancy: Pelvic inflammatory disease
• Objective
  • [Smear] PCR (+)
  • [Pathology] Inflammatory exudate with gram-negative diplococci: Cervicitis
  • [Pathology] Dilated tube lumen and edematous tubal plicae (acute), scarring and fusing tubal plicae (chronic): Salpingitis
  • [Pathology] Collection of pus in tube/ovary: Pyosalpinx, tubo-ovarian abscess
• Plan
  • IV ceftriaxone
  • Surgery: For tubo-ovarian abscess

Bacterial Vaginosis / 細菌性膣症

• Overview
  • Infection of lower genital tract caused by mainly Gardnerella vaginalis
• Subjective
  • Green-gray fishy vaginal discharge
  • Premature labor
• Objective
  • [Smear] Squamous cells covered with coccobacilli

Genital Candidiasis / カンジダ外陰腟炎

• Overview
  • Infection of lower genital tract caused by Candida, exogenous or endogenous (DM, antibiotics, pregnancy)
• Subjective
  • Pruritus, erythema, swelling, curdlike discharge
• Objective
  • [KOH] Pseudospores, hyphae
• Plan
  • Fluconazole (symptomatic case only)

Vaginal Trichomoniasis / 腟トリコモナス症

• Overview
  • Infection of lower genital tract caused by Trichomonas vaginalis
• Subjective
  • Pruritus, frothy yellow vaginal discharge, dysuria, dyspareunia
  • Red cervical/vaginal mucosa: Strawberry cervix
• Objective
  • [Smear] Flagellated ovoid protozoan
• Plan
  • Metronidazole

Breast Disorder / 乳房疾患

Breast Inflammatory Disorder / 乳房炎症性疾患

• Overview
  • Inflammation of breast due to various causes
• Subjective
  • [Acute mastitis] Breast erythema and pain, fever
  • [Squamous metaplasia] Painful erythematous subaerolar abscess, fistula opening on edge of areola
  • [Duct ectasia] Palpable periareolar mass, white nipple secretion
  • [Fat necrosis] Painless palpable mass
  • [Lymphocytic mastopathy] Palpable mass
• Objective
  • [Pathology, squamous metaplasia] Squamous metaplasia of lactiferous duct, keratin plug and duct rupture, chronic granulomatous inflammation
  • [Pathology, duct ectasia] Ectatic duct filled lipid-laden macrophage, periductal inflammation and fibrosis
  • [Pathology, fat necrosis] Chalky-white nodules, necrotic adipose tissue, chronic inflammatory cells
  • [Pathology, lymphocytic mastopathy] Collagenized stroma, atrophic ducts, lymphocytic infiltrate
  • [Pathology, granulomatous mastitis] Lobulocentric granulomatous inflammation
• Assessment
  • [Type] Acute mastitis: Acute bacterial infection of breast during breastfeeding, mostly due to staphylococcus aureus
  • [Type] Squamous metaplasia of lactiferous ducts: Metaplasia of lactiferous duct leading to recurrent subareolar abscess, related to smoking
  • [Type] Duct ectasia: Ectasia of lactiferous duct leading to periductal inflammation and fibrosis
  • [Type] Fat necrosis: Fat necrosis of breast, related to trauma or surgery
  • [Type] Lymphocytic mastopathy: Inflammation of lactiferous duct, related to autoimmune disease (type 1 DM, thyroid disease)
  • [Type] Granulomatous mastitis: Granulomatous inflammation of mammary lobules, localized or systemic (GPA, sarcoidosis, TB)
• Plan
  • [Acute mastitis] Antibiotics, continue lactation
  • [Squamous metaplasia] Drainage, surgical removal of involved duct
  • [Granulomatous mastitis] Antibiotics, steroid

Nonproliferative Breast Change / 非増殖性乳腺変化

• Overview
  • Benign nonproliferative changes in breast ductal/acinar epithelium (fibrocystic change)
• Subjective
  • Breast pain/tenderness/swelling: Cyclic change with menstruation
• Objective
  • [Ultrasound] Heterogenous echogenicity
  • [Mammograph] Dense breast with cysts
  • [Pathology] Cyst, fibrosis, adenosis, apocrine metaplasia

Proliferative Breast Disease / 増殖性乳腺疾患

• Overview
  • Benign proliferation of breast ductal/acinar epithelium (with or without atypia), increased risk of carcinoma
• Subjective
  • Breast mass/induration
  • Nipple discharge (bloody/serous): Intraductal papilloma
  • Gynecomastia: Often in puberty or cirrhosis
• Objective
  • [Mammograph] Density, calcification
  • [Pathology, typical] Epithelial hyperplasia, sclerosing adenosis, radial sclerosing lesion, intraductal papilloma
  • [Pathology, atypical] Atypical ductal hyperplasia, atypical lobular hyperplasia: Resembling DCIS/LCIS, partially involved duct/lobule

Breast Cancer / 乳癌

• Overview
  • Malignant neoplasm of breast ductal/acinar epithelium, related to estrogen exposure and genetic inheritance
  • [Somatic] Estrogen-dependent proliferation (luminal), PIK3CA mutation (luminal), HER2 amplification (HER2), TP53 mutation (TNBC)
  • [Germline] BRCA1 (TNBC), BRCA2 (luminal), TP53 (HER2), PTEN, STK11, CDH1, PALPB2, ATM, CHEK2 mutations
  • [Lobular] CDH1 mutation, loss of cohesion
• Subjective
  • Palpable mass
  • Nipple retraction/discharge/erosion, dimpling sign
  • Erythematous pruritic eruption with crust: Paget disease due to intra-epidermal spread
  • Orange peel-like skin: Inflammatory carcinoma due to dermal lymphatics involvement
  • Male breast cancer: Often BRCA2 germline mutation
• Objective
  • [Ultrasound] Posterior attenuation, irregular border
  • [Mammography] Density, spicula, microcalcification
  • [Pathology, DCIS] Proliferation limited to ducts/lobules, comedo (central necrosis/calcification), cribriform, micropapillary, papillary, Paget disease (clear cell in epidermis)
  • [Pathology, LCIS] Loosely cohesive rounded cells, signet ring cells
  • [Pathology, IDC] Tubules, solid nests, ragged sheets, stromal desmoplasia
  • [Pathology, ILC] Decohesive infiltrating tumor cells without tubules, signet ring cells
  • [Pathology, others] Mucin lake (mucinous), well-formed tubules (tubular), papillae (papillary), abundant cytoplasm (apocrine), intercellular fluid (micropapillary), solid sheets (medullary), spindle cell (metaplastic), eosinophilic material (secretory)
• Assessment
  • [Molecular type] Luminal A: ER (+), HER2 (-), low proliferation (Ki67↓)
  • [Molecular type] Luminal B: ER (+), HER2 (-), high proliferation (Ki67↑)
  • [Molecular type] HER2-enriched: HER2 (+)
  • [Molecular type] Basal-like (TNBC): ER (-), HER2 (-)
  • [Histologic type] Ductal carcinoma in situ (DCIS): Intraductal spreading, resembling ducts
  • [Histologic type] Lobular carcinoma in situ (LCIS): Intraductal spreading, resembling lobules
  • [Histologic type] Invasive ductal carcinoma (IDC): Stromal invasion, resembling ducts
  • [Histologic type] Invasive lobular carcinoma (ILC): Stromal invasion, resembling lobules
  • [Histologic type] Lobular/mucinous/tubular/papillary carcinoma (luminal), apocrine/micropapillary carcinoma (HER2), medullary/metaplastic/secretory carcinoma (TNBC)
  • [Prognostic factor] Lymph node metastases, distant metastasis, tumor size, locally advanced disease, lymphovascular invasion, inflammatory carcinoma, molecular subtype
• Plan
  • Breast-conserving surgery + radiotherapy: For most cases
  • Modified radical mastectomy (+ reconstruction): For locally advanced cases
  • Axillary lymph node dissection: If sentinel lymph node biopsy (+)
  • Chemotherapy (neoadjuvant/adjuvant): For highly proliferative tumors (luminal/HER2/TNBC)
  • Hormone therapy (tamoxifen, GnRH agonist, aromatase inhibitor): For ER-positive tumors (luminal/HER2)
  • Target therapy (trastuzumab, lapatinib): For HER2-amplified tumors (HER2)

Fibroadenoma / 線維腺腫

• Overview
  • Benign neoplasm of intralobular stroma, due to MED12 mutation
• Subjective
  • Well-defined mobile mass
• Objective
  • [Ultrasound] Well-defined homogeneous mass
  • [Mammograph] Well-defined shadow
  • [Pathology] Proliferated intralobular stroma, compressed epithelium

Phyllodes Tumor / 葉状腫瘍

• Overview
  • Benign (occasionally malignant) neoplasm of intralobular stroma, due to MED12 mutation (TERT if malignant)
• Subjective
  • Rapidly enlarging mass
• Objective
  • [Pathology] Proliferated stroma covered by epithelium (leaf-like), variable cellularity and mitotic rate
• Plan
  • Surgical excision

Obstetrics / 産科

Abnormal Early Pregnancy / 妊娠初期の異常

Spontaneous Abortion / 自然流産

• Overview
  • Pregnancy loss before 22 gestational week due to fetal (early) or maternal (late) factors
  • Fetal chromosomal anomaly: Aneuploidy, polypoidy, translocation
  • Uterine physical defect: Leiomyoma, polyp, malformation
  • Maternal systemic disorder: Luteal-phase defect, diabetes, hypertension, APS, coagulopathy
  • Infection: Toxoplasma, Mycoplasma, Listeria
• Subjective
  • Few vaginal bleeding, mild abdominal pain, closed cervical os: Threatened miscarriage
  • Vaginal bleeding, labor-like abdominal pain, open cervical os: Progressive miscarriage
• Objective
  • [Ultrasound] Gestational sac without embryo/fetus: Missed miscarriage
• Plan
  • Tocolytics: For threatened miscarriage
  • Curettage: For progressive/missed miscarriage

Ectopic Pregnancy / 異所性妊娠

• Overview
  • Extrauterine implantation of fertilized egg (mostly fallopian tube, also peritoneum/ovary/cervix)
  • Predisposing: Pelvic inflammatory disease, surgery history, intrauterine contraceptive device, assisted reproductive technology
• Subjective
  • Amenorrhea, abdominal pain, vaginal bleeding
  • Acute abdominal pain, hemorrhagic shock: Tubal rupture
• Objective
  • [Blood] hCG↑
  • [Ultrasound] Extrauterine gestational sac, intraperitoneal hemorrhage
  • [Pathology] Chorionic villi in fallopian tube
• Plan
  • Observation: Monitor hCG change
  • Methotrexate (local, systemic)
  • Salpingostomy, tubal resection

Hyperemesis Gravidarum / 妊娠悪阻

• Overview
  • Unresolved nausea/vomiting during pregnancy, related to endocrine changes
• Subjective
  • Nausea, vomiting: Not resolved after middle pregnancy
  • Weight loss
• Objective
  • [Urine] Ketone (+)
• Plan
  • Eat small amounts frequently
  • IV fluid with glucose, vitamin B1

Abnormal Late Pregnancy / 妊娠後期の異常

Placenta Previa / 前置胎盤

• Overview
  • Placenta implants in lower uterus near/over internal os, related to previous cesarean section and intrauterine surgery
• Subjective
  • [Pregnancy] Vaginal bleeding
  • [Delivery] Massive hemorrhage
• Objective
  • [Ultrasound] Placenta covering internal os
• Assessment
  • [Related] Vasa previa: Vessels lie across internal os, cause fetal distress during delivery
• Plan
  • Cesarean section

Placenta Accreta / 癒着胎盤

• Overview
  • Placental villi penetrate decidua and invade myometrium, related to placenta previa and previous cesarean section
• Subjective
  • Difficult placenta separation, severe postpartum bleeding
• Objective
  • [Ultrasound, MRI] Absent sonolucent zone, thinning of myometrium
• Assessment
  • [Type] Placenta accreta: Villi attach to myometrium
  • [Type] Placenta increta: Villi invade into myometrium
  • [Type] Placenta percreta: Villi penetrate through myometrium
• Plan
  • Hemostasis: Uterotonic agents, compression sutures, arterial ligation, arterial balloon occlusion
  • Hysterectomy: If failed placental separation or hemostasis

Placental Abruption / 常位胎盤早期剝離

• Overview
  • Separation of placenta from uterine wall before delivery, related to HDP, CAM, trauma
• Subjective
  • Abdominal pain, board-like uterine wall
  • Hemorrhagic shock, DIC: Severe case
• Objective
  • [CTG] Late deceleration
  • [Ultrasound] Retroplacental hematoma
  • [Blood] FDP↑, D-dimer↑
• Plan
  • Emergent cesarean section

Chorioamnionitis / 絨毛膜羊膜炎

• Overview
  • Ascending infection of chorion-amnion by bacteria
• Subjective
  • Fever, tachycardia, uterine tenderness, foul vaginal discharge
  • Preterm delivery: Due to cervical maturation, premature rupture of membrane, premature labor pain
• Objective
  • [Vaginal discharge] Lactobacillus↓, Bacteroides/Gardnerella↑, pH>4.5, granulotic elastase↑
  • [Blood] WBC↑
  • [Pathology] Neutrophilic infiltrate of chorion-amnion, cloudy amniotic fluid
• Assessment
  • [Stage] Bacterial vaginosis: Lactobacillus replaced by anaerobics (Bacteroides/Gardnerella)
  • [Stage] Subclinical chorioamnionitis: Vaginal discharge findings
  • [Stage] Clinical chorioamnionitis: Maternal infection symptoms
• Plan
  • Tocolytics, corticosteroids: Subclinical chorioamnionitis
  • Labor induction, cesarean section: Clinical chorioamnionitis

Cervical Insufficiency / 頸管無力症

• Overview
  • Cervix weakening and dilation in middle pregnancy
• Subjective
  • Miscarriage, preterm birth
• Objective
  • [Pelvic exam] Cervical effacement
  • [Ultrasound] Cervical shortening, internal os dilation
• Plan
  • Cervical cerclage

Premature Delivery / 早産

• Overview
  • Birth in gestational week <37, causes include chorioamnionitis, cervical insufficiency, multiple pregnancy
• Subjective
  • Regular uterine contraction, vaginal bleeding: Threatened premature delivery
  • Watery vaginal discharge, visible fetal presenting part: Premature rupture of membranes
• Objective
  • [Ultrasound] Cervical dilation and shortening: Threatened premature delivery
  • [Vaginal discharge] pH>7, AFP(+), IGFBP-1(+), fFN(+): Premature rupture of membranes
• Assessment
  • [Condition] Threatened premature delivery: Labor onset before 37 weeks
  • [Condition] Premature rupture of membranes: Amniotic sac rupture before labor onset
  • [Complication] Intraventricular hemorrhage, retinopathy of prematurity, respiratory distress syndrome, patent ductus arteriosus, hyperbilirubinemia: Due to incomplete development
  • [Complication] Cerebral palsy, sepsis, chronic lung disease, necrotizing enterocolitis: Due to fetal inflammatory response syndrome
• Plan
  • Tocolytics, corticosteroids: <34 weeks
  • Labor induction, cesarean section: >34 weeks, or intrauterine infection or fetal distress

Post-term Pregnancy / 過期産

• Overview
  • Birth in gestational week >41
• Assessment
  • [Complication] Non-reassuring fetal status: Due to oligohydramnios
  • [Complication] Meconium aspiration syndrome: Due to meconium staining
  • [Complication] Shoulder dystocia: Due to excessively large infant
• Plan
  • Labor induction

Abnormal Fetal Status / 胎児の異常

Twin Pregnancy / 双胎妊娠

• Overview
  • Fertilization of two ova (dizygotic) or division of one fertilized ovum (monozygotic)
• Objective
  • [Ultrasound] Two gestational sac: Dichorionic
  • [Ultrasound] One gestational sac, two embryos: Monochorionic
• Assessment
  • [Type] Dichorionic diamnionic: Dizytotic or monozygotic (early division)
  • [Type] Monochorionic diamnionic: Monozygotic (intermediate division)
  • [Type] Monochorionic monoamnionic: Monozygotic (late division)
  • [Complication] Spontaneous abortion, premature delivery, anemia, hypertensive disorders of pregnancy
  • [Complication] Twin-to-twin transfusion syndrome: Shunt between monochorionic twin lead to unbalanced blood flow and heart failure (recipient) or fetal growth restriction (donor)

Fetal Growth Restriction / 胎児発育不全

• Overview
  • Small-for-gestational-age fetus (weight <-1.5 SD)
  • [Fetal] Chromosomal abnormality, congenital anomaly, fetal infection
  • [Maternal] Preeclampsia, multiple pregnancy, alcohol, cigarette
  • [Placental] Placental infarction, placenta previa, umbilical vascular anomalies,
• Subjective
  • Symmetric growth restriction: Fetal factor
  • Asymmetric growth restriction (sparing of brain): Placental or maternal factor

Fetal Hydrops / 胎児水腫

• Overview
  • Accumulation of fluid in fetus
  • [Immune] Rh(-) mother immunized by previous RH(+) fetus RBC, IgG destruct subsequent RH(+) fetus RBC, hemolytic anemia, cardiac decompensation
  • [Nonimmune] Cardiovascular defect (malformation, arrhythmia), chromosomal anomaly (45X, trisomy), fetal anemia (homozygous α-thalassemia, B19 infection)
• Subjective
  • Generalized edema (hydrops fetalis)
  • Pleural fluid, peritoneal fluid, postnuchal fluid (cystic hydroma)
  • Jaundice, kernicterus: Immune hydrops
• Objective
  • [Ultrasound] MCA peak velocity↑: Compensation for anemia
  • [Blood] Indirect Coombs test (+): Presence of antibody
• Assessment
  • [Type] Immune hydrops
  • [Type] Nonimmune hydrops
• Plan
  • Intrauterine fetal transfusion: For severe fetal anemia or hydrops
  • Anti-D antibody: For maternal isoimmunization

Polyhydramnios / 羊水過多症

• Overview
  • Excessive amniotic fluid (>800mL)
  • Causes: Idiopathic, gestational diabetes, gastrointestinal atresia (esophageal, duodenal), CNS anomaly (ancephaly, spina bifida)
• Subjective
  • [Maternal] Abdominal distension, shortness of breath
• Objective
  • [Ultrasound] AFP >8cm, AFI >24cm

Oligohydramnios / 羊水過少症

• Overview
  • Insufficient amniotic fluid (<100mL)
  • Causes: Premature rupture of membranes, renal agenesis (Potter syndrome)
• Subjective
  • [Fetal] Pulmonary hypoplasia, limb deformity
• Objective
  • [Ultrasound] AFP <2cm, AFI <5cm

Complicated Pregnancy / 合併症妊娠

Gestational Diabetes Mellitus / 妊娠糖尿病

• Overview
  • Pregnancy complicated with preexisting (pregestational) or newly-onset (gestational) diabetes
  • Due to insulin resistance resulting from hormonal change (hPL)
• Subjective
  • [Fetal] Macrosomnia, hypoglycemia, malformation, stillbirth: At birth
  • [Fetal] Obesity, diabetes: Long term
• Objective
  • [Blood] Fasting glucose ≥ 92, OGTT 1hr ≥ 180, OGTT 2hr ≥ 153: Gestational DM
  • [Blood] Fasting glucose ≥ 126, OGTT 2hr ≥ 200, HbA1c ≥ 6.5%: Overt DM in pregnancy
• Assessment
  • [Type] Pregestational DM: DM diagnosed before pregnancy
  • [Type] Gestational DM: Elevated glucose during pregnancy
  • [Type] Overt DM in pregnancy: DM diagnosed during pregnancy
  • [Course] Usually resolve after delivery, often develop DM years later
• Plan
  • Diet therapy
  • Insulin therapy

Hypertensive Disorders of Pregnancy / 妊娠高血圧症候群

• Overview
  • Pregnancy complicated with hypertension with/without organ dysfunction, related to aging and obesity
  • [Mechanism] Abnormal trophoblastic implantation, vascular remodeling failure
  • [Mechanism] Placental hypoxia, release of sFlt1 (antagonize VEGF/PGI2) and endoglin (antagonize TGFβ/NO)
  • [Mechanism] Vasoconstriction, hyperpermeability, hypercoagulability
  • [Mechanism] Hypertension, kidney damage (preeclampsia), brain damage (eclampsia), liver damage (HELLP)
• Subjective
  • Hypertension, edema, proteinuria: Preeclampsia
  • Headache, visual disturbance, convulsions: Eclampsia
  • Acute abdominal pain, fatigue, nausea: HELLP
  • Fetal growth restriction, non-reassuring fetal status
• Objective
  • [Urine] Protein (+), P/C ratio↑: Preeclampsia
  • [MRI] Cerebral edema (posterior reversible encephalopathy syndrome): Eclampsia
  • [Blood] Bilirubin/LDH↑, AST/ALT↑, platelet↓: HELLP
  • [Patho, placenta] Decidual vasculopathy, villous infarction, syncytial knots
  • [Patho, organs] Endothelial swelling, fibrin deposition, intraparenchymal hemorrhage
• Assessment
  • [Type] Preeclampsia: Proteinuria
  • [Type] Eclampsia: Convulsion
  • [Type] HELLP syndrome: Hemolysis, elevated liver enzyme, low platelet
  • [Course] Usually resolve after delivery
• Plan
  • Delivery: If possible
  • Antihypertensive, MgSO4: Control hypertension/convulsion
  • Airway, oxygen: For convulsion episode

Transplacental Infection / 経胎盤感染

• Overview
  • Transplacental infection from mother to fetus by virus/bacteria/parasite
• Subjective
  • [Rubella] Cataract, cardiac anomaly (PDA), hearing loss
  • [CMV] Microcephaly, intracranial calcification, hepatosplenomegaly, jaundice, petechiae, hearing loss, chorioretinitis
  • [B19] Hydrops fetalis, spontaneous abortion, stillbirth
  • [Zika] Microcephaly, intracranial calcification, arthrogryposis, ocular abnormality
  • [Treponema] Hepatosplenomegaly, rash, osteochondritis, rhinitis (snuffles), saddle nose, Hutchinson teeth, saber shins
  • [Toxoplasma] Chorioretinitis, hydrocephalus, intracranial calcification, seizure, hepatosplenomegaly
• Assessment
  • [Pathogen] Rubella virus
  • [Pathogen] Cytomegalovirus
  • [Pathogen] Parvovirus B19
  • [Pathogen] Zika virus
  • [Pathogen] Treponema pallidum
  • [Pathogen] Toxoplasma gondii

Intrapartum Infection / 産道感染

• Overview
  • Intrapartum infection from mother to fetus by virus/bacteria/fungus
• Subjective
  • [HSV] Neonatal herpes, mortality
  • [VZV] Neonatal varicella, mortality
  • [HPV] Laryngeal papilloma
  • [HBV] Carrier, chronic hepatitis
  • [HCV] Carrier, chronic hepatitis
  • [HIV] Carier, AIDS
  • [GBS] Pneumonia, meningitis, sepsis
  • [Gonococcus] Suppurative conjunctivitis
  • [Chlamydia] Conjunctivitis, pneumonitis
  • [Candida] Oral thrush
• Assessment
  • [Pathogen] Herpes simplex virus
  • [Pathogen] Varicella-zoster virus
  • [Pathogen] Human papilloma virus (6, 11)
  • [Pathogen] Hepatitis B virus
  • [Pathogen] Hepatitis C virus
  • [Pathogen] Human immunodeficiency virus
  • [Pathogen] Group B streptococcus
  • [Pathogen] Neisseria gonorrhea
  • [Pathogen] Chlamydia trachomatis
  • [Pathogen] Candida albicans

Abnormal Labor / 分娩の異常

Abnormal Labor Mechanism / 分娩機転の異常

• Overview
  • Abnormality of uterine contraction, fetal presentation, fetal attitude, fetal rotation, and others
• Assessment
  • [Contraction] Weak: Interval >6min, duration <40sec
  • [Contraction] Strong: Interval <1min, duration >120sec
  • [Presentation] Breech: Head up
  • [Presentation] Transverse: Head lateral
  • [Attitude] Vertex: Anterior + posterior fontanelle presenting
  • [Attitude] Bregmatic: Anterior fontanelle presenting
  • [Attitude] Brow: Forehead presenting
  • [Attitude] Face: Eye/nose presenting
  • [Rotation] High sagittal: Sagittal suture in longitudinal axis at high position
  • [Rotation] Deep transverse: Sagittal suture in transverse axis at low position
  • [Rotation] Occiput posterior: Occiput facing posterior direction
  • [Entering] Anterior parietal: Sagittal suture displaced posteriorly
  • [Entering] Posterior parietal: Sagittal suture displaced anteriorly
  • [Canal] Cephalopelvic disproportion: Head - pelvis mismatch
  • [Canal] Shoulder dystocia: Shoulder - pubic symphysis mismatch
  • [Umbilical] Forelying: Cord lying below fetus
  • [Umbilical] Prolapse: Cord prolapse out
• Plan
  • Cesarean section
  • Labor induction

Non-Reassuring Fetal Status / 胎児機能不全

• Overview
  • Abnormality of fetal evaluation results, may indicate fetal hypoxia and acidosis
• Objective
  • [CTG] Baseline variability decrease/absence, sinusoidal pattern, bradycardia, late/variable/prolonged deceleration
• Assessment
  • [Complication] Hypoxic ischemic encephalopathy (cerebral palsy)
• Plan
  • Lateral position
  • Adjust uterotonics, tocolysis agents
  • Oxygen, IV fluids
  • Labor induction: If cervix opened and head descended
  • Cesarean section: Otherwise

Postpartum Hemorrhage / 分娩後異常出血

• Overview
  • Massive bleeding during/after delivery, due to placental separation, birth canal injury, DIC
• Subjective
  • Massive bleeding
  • Pallor, perspiration, cyanosis, hypotension, tachycardia, tachypnea
  • Highly-positioned and soft uterus: Atonic bleeding
  • Sudden severe abdominal pain: Uterine rupture
• Objective
  • [Blood] Platelets↓, FDP↑, D-dimer↑: DIC
• Assessments
  • [Causes] Atonic bleeding: Poor uterine contraction due to myometrium fatigue or placenta retention
  • [Causes] Perineal laceration: Tears involving skin (1), muscle (2), anal sphincter (3), rectal mucosa (4)
  • [Causes] Cervical laceration: Tears involving cervix
  • [Causes] Uterine rupture: Rupture of uterus due to surgical history or excessive uterotonics
  • [Causes] Uterine inversion: Inversion of uterus
  • [Causes] Placenta accreta: Difficult separation of placenta
  • [Causes] Placental abruption: Lead to DIC due to tissue factor entering
  • [Causes] Amniotic fluid embolism: Lead to DIC due to tissue factor entering
• Plan
  • Blood transfusion: RBC, platelets, FFP, antithrombin (if DIC)
  • Non-surgical hemostasis: Astriction (hand, balloon), suture, uterotonics, TAE, arterial balloon catheter
  • Surgical hemostasis: Arterial ligation, compression suture, hysterectomy
  • Shock management: Airway, oxygen, fluid, vasopressor
  • Autologous blood donation: Preventive

Amniotic Fluid Embolism / 羊水塞栓症

• Overview
  • Amniotic fluid entering maternal bloodstream, lead to cardiopulmonary collapse (physical embolism) and DIC (anaphylaxis-like)
• Subjective
  • Acute chest pain, dyspnea, shock, respiratory arrest, cardiac arrest: Cardiopulmonary collapse
  • Massive hemorrhage and shock: DIC
• Objective
  • [Pathology] Fetal components (mucin, ZnCP-1, STN) in pulmonary artery
• Plan
  • CPR, anti-shock therapy, anti-DIC therapy

Abnormal Puerperium / 産褥の異常

Subinvolution of Uterus / 子宮復古不全

• Overview
  • Delayed involution of uterus, often due to retention of placental tissue
• Subjective
  • Large soft uterus
  • Persistent lochia rubra
• Plan
  • Uterotonic agent, uterine curettage

Puerperal Fever / 産褥熱

• Overview
  • Postpartum fever, often due to infection of of uterus/pelvis
• Subjective
  • Fever: ≥ 2 days
  • Lower abdominal pain, foul-smelling lochia
• Plan
  • Antibiotics, uterine curettage

Venous Thromboembolism / 静脈血栓塞栓症

• Overview
  • Venous thromboembolism during/after pregnancy, related to obesity and cesarean section
• Subjective
  • [DVT] Pain and swelling in one leg
  • [PTE] Acute chest pain, dyspnea
• Objective
  • [Ultrasound, DVT] Deep vein thrombus, absent blood flow
  • [Blood, PTE] PaO2↓, PaCO2↓
  • [CT, PTE] Pulmonary artery thrombus, absent blood flow
• Assessment
  • [Condition] Deep vein thrombosis
  • [Condition] Pulmonary thromboembolism
• Plan
  • Anticoagulation, thrombolytics
  • Oxygen therapy, catheter embolectory: Pulmonary embolism
  • Early ambulation, elastic stockings: Prevention

Trophoblastic Disorder / 絨毛性疾患

Hydatidiform Mole / 胞状奇胎

• Overview
  • Abnormal proliferation of chorionic villi
  • [Complete] Fertilization of empty ovum with one sperm + duplication (or two sperm)
  • [Partial] Fertilization of normal ovum with two sperm
• Subjective
  • Abnormal vaginal bleeding, hyperemesis
  • Spontaneous abortion, uterine enlargement
• Objective
  • [Blood] hCG↑
  • [Ultrasound] Vesicular pattern, luteal cyst
  • [Pathology] Grapelike mass, villous edema, trophoblastic proliferation
• Assessment
  • [Type] Complete mole: 46XX / 46XY, without fetal tissue, higher malignancy risk
  • [Type] Partial mole: 69XXX / 69XXY, with fetal tissue, lower malignancy risk
  • [Type] Invasive mole: Invasion into myometrium
• Plan
  • Curettage, monitor hCG
  • Chemotherapy: For invasive mole

Choriocarcinoma / 絨毛癌

• Overview
  • Malignant neoplasm of trophoblastic cells
  • Following complete mole, abortion, normal pregnancy
• Subjective
  • Abnormal vaginal bleeding
  • Cough, bloody sputum: Lung metastasis
• Objective
  • [Blood] hCG↑
  • [Ultrasound] Hypervascular tumor
  • [Pathology] Proliferating trophoblasts without villi, invading myometrium
• Assessment
  • [Related] Placental site trophoblastic tumor: Neoplasm of intermediate trophoblasts, good prognosis
• Plan
  • Chemotherapy (etoposide, methotrexate, dactinomycin, cyclophosphamide, vincristine): Good respond

Pediatrics / 小児科