Genital Lesions in Dermatopathology
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1 Genital Lesions in Dermatopathology Janis M. Taube, MD Director of Dermatopathology Associate Professor of Dermatology and Pathology Johns Hopkins University SOM
2 Overview Vulvovaginal pathology Inflammatory Spongiotic and psorasiform dermatitis Lichenoid pattern lichen sclerosus lichen amyloid lichen planus Zoon s mucositis/dermatitis In situ and invasive carcinoma Two types of VIN and squamous cell carcinoma BCCs of the vulva Paget s disease Lesions of anogenital mammary-like glands Miscellaneous Verruciform xanthoma Scrotal lesions Paget s disease of the breast
3 Contact Dermatitis Common condition, increasing with chronicity Irritant (exposure to chemical or physical agents) *most common Allergic (cell-mediated following sensitization) Medications Preservatives and fragrances in products Nickel or rubber acute, subacute and chronic phases
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5 Spongiotic and Psorasiform Pattern on Vulva Contact dermatitis Psoriasis Lichen simplex chronicus Vulvovaginal candidiasis Tinea infection Extramammary Paget s disease
6 Vulvar psoriasis 5% of women with vulvar symptoms Chronic, relapsing condition Multiple forms: Classic and pustular forms, either generalized or localized to vulva Inverse psoraisis Cutaneous (rather than mucosal) vulva in all forms Mons pubis Labia majora
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9 need strong clinical input to secure diagnosis of psoriasis at this site biopsy is not necessary if clinically diagnosed unless lesion is treatmentresistant
10 DDx includes Paget s disease (which may be subtle) Beware! Erythematous vulvar eruptions that are: Therapy resistant Eroded Unilateral
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12 CK7
13 Lichen Sclerosus Chronic fibrosing disease of the anogenital skin Labia majora is most common site Relapsing and remitting course Obliteration and stenosis over time Bimodal age peak at pre-menarche and post-menopause Lesions start as ivory white papules and macules that coalesce Increased risk for developing non-hpvrelated SCC (2-5%)
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15 Histology of Early LS Basement membrane thickening Appendageal hyperkeratosis and hypergranulosis Superficial vascular ectasia Lymphocyte tagging along basement membrane Modified from Regauer S, et al. Histopathology, 2005
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18 CK5/6
19 Diagnosis: Primary, localized lichen amyloidosis of the vulva
20 Lichen Amyloidosis Most common form of primary localized cutaneous amyloidosis Typically seen on the shins Papules may coalesce into thickened plaques Often shows associated LSC-type changes
21 Lichen planus 50% of women who have lichen planus have genital involvement Very commonly associated with oral lesions Erosive LP is the most common cause of noninfectious erosive vulvar disease Scarring secondary to LP can lead to narrowing of the introitus DDx: early lichen sclerosus, lichenoid drug eruption
22 Vulvar Lichen Planus Erosive* (most common) papulosquamous Anatomic site Mucosal surface Hair-bearing skin (labia majora) Histology Often non-specific ulceration* Like classic cutaneous LP hypertrophic Perineal and perianal regions Like classic hypertrophic LP *Suggest additional sampling adjacent, inflamed, but nonulcerated areas. If present, sample white reticulated areas. -DIF may also be of use
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27 CK903 Reported association of erosive LP and SCC is 2-3% of cases.
28 Plasma cell vulvitis (Zoon s vulvitis) 1952 Zoon first made his histologic description in the foreskin 1957 Garnier described a rare condition of erythematous plaques on the vulva in postmenopausal women vulvitis circumscripta plasmacellularis idiopathic lymphoplasmacellular mucositisdermatitis
29 Plasma cell vulvitis (Zoon s vulvitis) Rare, chronic inflammatory condition in classically in post-menopausal women Vestibule and labia minora Single erythematous plaque: glistening, redorange-brown, and resembling purpura Vulvar soreness, pruritic, burning, discharge, and bleeding Clinical DDx: VIN, Paget s disease, Fixed drug eruption
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31 Retrospective histopathologic re-evaluation of 18 cases of plasma cell vulvitis Lichenoid infiltrate with plasma cells: >50% of plasma cells or 25-50% plasma cells with epithelial atrophy and hemosiderin deposition <25% may be attributed to mucosal site lozenge-shaped keratinocytes were rarely observed Virgili A, et al. J Reprod Med, 2005
32 Overview Vulvovaginal pathology Inflammatory Spongiotic and psorasiform dermatitis Lichenoid pattern lichen sclerosus lichen amyloid lichen planus Zoon s mucositis/dermatitis In situ and invasive carcinoma Two types of VIN and squamous cell carcinoma BCCs of the vulva Paget s disease Lesions of anogenital mammary-like glands Miscellaneous Verruciform xanthoma Scrotal lesions Paget s disease of the breast
33 Vulvar SCC Basaloid SCC Keratinizing SCC Age Younger females Older females Distribution Often multifocal Usually unifocal Frequency 1/3 of cases 2/3 of cases Morphology Basaloid-Warty Kertatinizing Associated VIN Common, classic-type Uncommon, differentiated (simplex) type Association with HPV Yes (most often HPV 16, 18), p16 IHC positive in block-like pattern Association with lichen sclerosus No No Yes
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36 HPV-WS ISH
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39 P16 IHC as a surrogate marker of high-risk HPV infection Positive predictive value of diffuse, block-like pattern is 95-97% Modified from Riethdorf S, et al. Hum Pathol 2004
40 P16 IHC and two types of vulvar SCC Diffuse, block-like pattern in warty, basaloid SCC Patchy, heterogeneous pattern in keratinizing SCC
41 Differentiated (simplex) VIN Rarely diagnosed in its pure form Usually identified adjacent to non-hpv SCC Older women, often background Lichen Sclerosus?prognostic significance keratinizing SCC thought to have a worse prognosis than basaloid variants
42 Taube JM, Am J. Dermatopathol, 2011
43 Proposal for reclassification of VIN
44 Proposal for reclassification of VIN DVIN-not graded Current WHO: Classic VIN is graded I, II, and III (like CIN) CINI > CINIII VIN1<VINIII ISSVD proposed VIN I category dropped, and combining VINII and VINIII VINI is not reproducible, natural history unknown VINII and VINIII no treatment difference
45 Podophyllin-treatment reaction (most pronounced within hours)
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47 14/14 patients were immunocompromised: 13 had HIV and 1 was transplant patient
48 H&E p16 11/14 of cases showed high-grade VIN and condyloma to be adjacent HPV 16 HPV 6/11
49 HSIL with condylomatous architecture By ISH contained only HR-HPV, negative for HPV6/11
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51 H&E p16
52 HPV- 6/11 HPV- 16
53 Right lateral perianal mass 39 y/o man
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57 Vulvar BCC 3-5% of vulvar malignancies Not associated with VIN or HPV May have squamoid areas, and is likely to be confused with more common HPV-related basaloid SCC
58 Treatment Differences LN metastases Surgery BCC Singular cases with high risk features* Conservative reexcision SCC 15% of cases >1 mm deep Wide excision and sentinel lymph node *size >2 cm or involvement of subcutis, Benedet, et al. Obstet Gynecol. 1997
59 Basaloid SCC of Vulva p16 p16 BerEP4 HPV-WS ISH
60 Elwood H, et al. Am J Surg Path, 2014 Vulvar BCC H&E H&E p16 p16 BerEP4 HPV-WS ISH
61 Paget s disease of the Vulva Intraepidermal adenocarcinoma with tumor cells involving the epidermis and sometimes underlying skin adnexal structures Typically CK7+, CEA+ and Cam5.2+ The minority are secondary to a carcinoma of the cervix, rectum, or bladder Immunophenotype reflects underlying primary carcinoma
62 Primary EMPD Vulva 7 th decade Labia majora>labia minora>clitoris Primary disease is slowly progressive and rarely metastasizes Approx 30% of cases have dermal invasion, prognostic significance unknown
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64
65 Cam5.2
66 CK903
67 Overview Vulvovaginal pathology Inflammatory Spongiotic and psorasiform dermatitis Lichenoid pattern lichen sclerosus lichen amyloid lichen planus Zoon s mucositis/dermatitis In situ and invasive carcinoma Two types of VIN and squamous cell carcinoma BCCs of the vulva Paget s disease Lesions of anogenital mammary-like glands Miscellaneous Verruciform xanthoma Scrotal lesions Paget s disease of the breast
68 Anogenital mammary-like glands Located in sulcus between labia minora and majora Normal histology ranges from simple glandular structures to complex lobular units Demonstrate changes of sclerosing adenosis, columnar cell change, UDH, ADH, lactating adenoma
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71 Kazakov D, et al. Adv Anat Pathol, 2011
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74 Overview Vulvovaginal pathology Inflammatory Spongiotic and psorasiform dermatitis Lichenoid pattern lichen sclerosus lichen amyloid lichen planus Zoon s mucositis/dermatitis In situ and invasive carcinoma Two types of VIN and squamous cell carcinoma BCCs of the vulva Paget s disease Lesions of anogenital mammary-like glands Miscellaneous Verruciform xanthoma Scrotal lesions Paget s disease of the breast
75 Verruciform Xanthoma Slow-growing, painless, solitary exophytic tumors 0.5 to 2.0 cm in size HPV has not been detected
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79 Overview Vulvovaginal pathology Inflammatory Spongiotic and psorasiform dermatitis Lichenoid pattern lichen sclerosus lichen amyloid lichen planus Zoon s mucositis/dermatitis In situ and invasive carcinoma Two types of VIN and squamous cell carcinoma BCCs of the vulva Paget s disease Lesions of anogenital mammary-like glands Miscellaneous Verruciform xanthoma Scrotal lesions Paget s disease of the breast
80 Survey of 25 yrs JHH archives Category Soft tissue lesions (liposarcoma most common) N=364 total 77 (21%) EIC 46 (16%) Inflammatory lesions 36 (13%) Benign keratoses 26 (9%) Melanocytic lesions 20 (7%) SCC 20 (7%) Fournier s gangrene 19 (7%) Fibroepithelial polyps 16 (6%) Adnexal tumors 13 (5%) Abscess 13 (5%) Idiopathic scrotal calcinosis 8(3%) Paget s disease 4 (1%) Angiokeratoma 4 (1%) Search terms: scrotum and scrotal Elwood H, Taube JM, unpublished data
81 Liposarcoma Majority arise in the spermatic cord and testicular tunics Mean age 63 years Tumors range in size from 3-30 cm 2/3 are atypical lipomatous tumor/wdl 1/3 de-differentiated or myxoid/round cell variant
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84 Localized Lymphedema Reactive, pseudotumor/pseudosarcoma Associated with obesity Secondary to obstruction of lymphatic flow
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87 Overview Vulvovaginal pathology Inflammatory Spongiotic and psorasiform dermatitis Lichenoid pattern lichen sclerosus lichen amyloid lichen planus Zoon s mucositis/dermatitis In situ and invasive carcinoma Two types of VIN and squamous cell carcinoma BCCs of the vulva Paget s disease Lesions of anogenital mammary-like glands Miscellaneous Verruciform xanthoma Scrotal lesions Paget s disease of the breast
88 Paget s disease of the nipple
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90 Approx 5% of Paget s cases have dermal invasion No correlation with increasing tumor stage of underlying breast carcinoma Depth of invasion measured from DEJ Clinical significance is unclear, thus patients are managed according to the underlying carcinoma Am J Surg Path, 2014
91 Her2/neu
92 DDx: Toker cell hyperplasia Found in normal epidermis of nipple (seen in 10% of patients on routine stains, 80% of patients with CK7). Usually found at opening of lactiferous ducts. Bland cells with condensed chromatin. Lack prominent nucleoli. HER2/neu negative. Garijo, MF, et al. Histol Histopathol, 2009
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94 CK7
95 DDx: Pagetoid dyskeratosis
96 CK903
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