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 lesions Non-Neoplastic Spongiotic and psorasiform dermatitis Lichenoid pattern lichen sclerosus lichen amyloid lichen planus Zoon s mucositis/dermatitis Verruciform xanthoma Neoplastic lesions Two types of VIN and squamous cell carcinoma Podophylin-treatment reaction C0-existing nigh-grade VIN and condyloma BCCs of the vulva Scrotal lesions
3 Spongiotic and Psorasiform Pattern on Vulva Contact dermatitis Psoriasis Lichen simplex chronicus Vulvovaginal candidiasis Tinea infection Extramammary Paget s disease
4 Spongiotic and Psorasiform Pattern on Vulva Contact dermatitis Psoriasis Lichen simplex chronicus Vulvovaginal candidiasis Tinea infection Extramammary Paget s disease PAS stains
5 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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7 need strong clinical input to secure diagnosis of psoriasis at this site Features on bx are often obscured due to LSC or secondary infection biopsy is not necessary if clinically diagnosed unless lesion is treatmentresistant
8 5% of women with vulvar symptoms Chronic, relapsing condition Multiple forms: Classic and pustular forms, either generalized or localized to vulva Inverse psoraisis Vulvar psoriasis Cutaneous (rather than mucosal) vulva in all forms
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11 DDx includes Paget s disease (which may be subtle) Beware! Erythematous vulvar eruptions that are: Therapy resistant Eroded Unilateral
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13 CK7
14 Overview Vulvovaginal lesions Non-Neoplastic Spongiotic and psorasiform dermatitis Lichenoid pattern lichen sclerosus lichen amyloid lichen planus Zoon s mucositis/dermatitis Verruciform xanthoma Neoplastic lesions Two types of VIN and squamous cell carcinoma BCCs of the vulva Paget s disease Scrotal lesions
15 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%)
16 Established Lichen Sclerosus
17 Histology of Early LS Basement membrane thickening Appendageal hyperkeratosis and hypergranulosis Superficial vascular ectasia Lymphocyte tagging along basement membrane Regauer S, et al. Histopathology, 2005
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19 Diagnosis? CK5/6
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 Genital Lichen Planus
22 Genital 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 DDx: early lichen sclerosus, lichenoid drug eruption
23 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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28 CK903 Reported association of erosive LP and SCC is 2-3% of cases.
29 Plasma cell vulvitis (Zoon s vulvitis)
30 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
31 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
32 Histologic Features Atrophic epidermis Spongiosis Loss of stratum corneum Prominent vessels (extravasated RBCs) Classic description: Plasma cells and lozenge-shaped keratinocytes
33 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
34 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 Identified 16/18 patients in retrospective study Virgili A, et al. J Reprod Med, 2005
35 Overview Vulvovaginal lesions Non-Neoplastic Spongiotic and psorasiform dermatitis Lichenoid pattern lichen sclerosus lichen amyloid lichen planus Zoon s mucositis/dermatitis Verruciform xanthoma Neoplastic lesions Two types of VIN and squamous cell carcinoma Podophylin-treatment reaction C0-existing nigh-grade VIN and condyloma BCCs of the vulva Scrotal lesions
36 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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38
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40 Overview Vulvovaginal lesions Non-Neoplastic Spongiotic and psorasiform dermatitis Lichenoid pattern lichen sclerosus lichen amyloid lichen planus Zoon s mucositis/dermatitis Verruciform xanthoma Neoplastic lesions Two types of VIN and squamous cell carcinoma Podophylin-treatment reaction C0-existing nigh-grade VIN and condyloma BCCs of the vulva Scrotal lesions
41 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
42 Basaloid SCC HPV-WS ISH
43 Keratinizing SCC
44 P16 IHC as a surrogate marker of Uneven staining (combined strongly staining and weak/no staining) high-risk HPV infection Homogeneous nuclear and cytoplasmic 175 archival vulvar lesions, stained with p16 IHC Positive predictive value of diffuse, block-like pattern is 95-97% Modified from Riethdorf S, et al. Hum Pathol 2004
45 P16 IHC and two types of vulvar SCC Diffuse, block-like pattern in warty, basaloid SCC Patchy, heterogeneous pattern in keratinizing SCC
46 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
47 Taube JM, Am J. Dermatopathol, 2011
48 Overview Vulvovaginal lesions Non-Neoplastic Spongiotic and psorasiform dermatitis Lichenoid pattern lichen sclerosus lichen amyloid lichen planus Zoon s mucositis/dermatitis Verruciform xanthoma Neoplastic lesions Two types of VIN and squamous cell carcinoma Podophylin-treatment reaction C0-existing nigh-grade VIN and condyloma BCCs of the vulva Scrotal lesions
49 Podophyllin-treatment reaction (most pronounced within hours) Making the diagnosis: 1) Background features of condyloma 2) Clinical history 3) P16 IHC as adjunct
50 14/14 patients were immunocompromised: 13 had HIV and 1 was transplant patient
51 H&E p16 11/14 of cases showed high-grade VIN and condyloma to be adjacent HPV 16 HPV 6/11
52 Focal HSIL in background condyloma H&E p16
53 Focal HSIL in background condyloma HPV- 6/11 HPV- 16
54 HSIL with condylomatous architecture By ISH contained only HR-HPV, negative for HPV6/11
55 Vulvar BCC
56 Vulvar mass 39 y/o woman
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58 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
59 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
60 Basaloid SCC of Vulva p16 p16 BerEP4 HPV-WS ISH
61 Elwood H, et al. Am J Surg Path, 2014 Vulvar BCC H&E H&E p16 p16 BerEP4 HPV-WS ISH
62 Overview Vulvovaginal lesions Non-Neoplastic Spongiotic and psorasiform dermatitis Lichenoid pattern lichen sclerosus lichen amyloid lichen planus Zoon s mucositis/dermatitis Verruciform xanthoma Neoplastic lesions Two types of VIN and squamous cell carcinoma Podophylin-treatment reaction C0-existing nigh-grade VIN and condyloma BCCs of the vulva Scrotal lesions
63 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
64 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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66 DDx: Localized Lymphedema Reactive, pseudotumor/pseudosarcoma Associated with obesity Secondary to obstruction of lymphatic flow
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69 Questions?
70 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
71 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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74 Cam5.2
75 CK903
76 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
77 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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80 Kazakov D, et al. Adv Anat Pathol, 2011
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83 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
84 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
85 Paget s disease of the nipple
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87 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
88 Her2/neu
89 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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91 CK7
92 DDx: Pagetoid dyskeratosis
93 CK903
94 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
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