Genital Lesions in Dermatopathology - pathcme.com · cutaneous LP. Likeclassic hypertrophic LP...
Transcript of Genital Lesions in Dermatopathology - pathcme.com · cutaneous LP. Likeclassic hypertrophic LP...
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Genital Lesions in Dermatopathology
Janis M. Taube, MDDirector of Dermatopathology
Associate Professor of Dermatology and PathologyJohns Hopkins University SOM
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OverviewVulvovaginal 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 lesionsPaget’s disease of the breast
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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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Spongiotic and PsorasiformPattern on Vulva
• Contact dermatitis• Psoriasis• Lichen simplex chronicus• Vulvovaginal candidiasis• Tinea infection• Extramammary Paget’s disease
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• 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
Vulvar psoriasis
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•need strong clinical input to secure diagnosis of psoriasis at this site•biopsy is not necessary if clinically diagnosed unless lesion is treatment-resistant
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DDx includes Paget’s disease (which may be subtle)
Beware!Erythematousvulvar eruptions that are:
•Therapy resistant•Eroded•Unilateral
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CK7
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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-HPV-related SCC (2-5%)
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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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CK5/6
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Diagnosis: Primary, localized lichen amyloidosis of the vulva
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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
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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 non-
infectious erosive vulvar disease• Scarring secondary to LP can lead to narrowing of
the introitus• DDx: early lichen sclerosus, lichenoid drug
eruption
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Erosive* (most common)
papulosquamous hypertrophic
Anatomic site Mucosal surface Hair-bearing skin (labia majora)
Perineal and perianal regions
Histology Often non-specific ulceration*
Like classic cutaneous LP
Like classic hypertrophic LP
*Suggest additional sampling adjacent, inflamed, but non-ulcerated areas. If present, sample white reticulated areas.-DIF may also be of use
Vulvar Lichen Planus
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Reported association of erosive LP and SCC is 2-3% of cases.
CK903
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1952– Zoon first made his histologic description in the foreskin
1957—Garnier described a rare condition of erythematous plaques on the vulva in post-menopausal women
“vulvitis circumscripta plasmacellularis”“idiopathic lymphoplasmacellular mucositis-
dermatitis”
Plasma cell vulvitis (Zoon’s vulvitis)
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Plasma cell vulvitis (Zoon’s vulvitis)
• Rare, chronic inflammatory condition in classically in post-menopausal women
• Vestibule and labia minora• Single erythematous plaque: glistening, red-
orange-brown, and resembling purpura• Vulvar soreness, pruritic, burning, discharge,
and bleeding• Clinical DDx: VIN, Paget’s disease, Fixed drug
eruption
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• 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
Retrospective histopathologic re-evaluation of 18 cases of plasma cell vulvitis
Virgili A, et al. J Reprod Med, 2005
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OverviewVulvovaginal 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 lesionsPaget’s disease of the breast
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Vulvar SCCBasaloid 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
No
Association with lichen sclerosus
No Yes
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HPV-WS ISH
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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
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Diffuse, block-like pattern in warty, basaloid SCC
Patchy, heterogeneous pattern in keratinizing SCC
P16 IHC and two types of vulvar SCC
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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
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Taube JM, Am J. Dermatopathol, 2011
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Proposal for reclassification of VIN
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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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Podophyllin-treatment reaction (most pronounced within 48-72 hours)
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14/14 patients were immunocompromised: 13 had HIV and 1 was transplant patient
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11/14 of cases
showed high-grade
VIN and condyloma
to be adjacent
H&E p16
HPV 6/11HPV 16
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HSIL with condylomatous architecture
By ISH contained only HR-HPV, negative for HPV6/11
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H&E p16
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HPV-6/11
HPV-16
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Right lateral perianal mass 39 y/o man
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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
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BCC SCC
LN metastases Singular cases with high risk features*
15% of cases >1 mm deep
Surgery Conservative re-excision
Wide excision and sentinel lymph
node
Treatment Differences
*size >2 cm or involvement of subcutis, Benedet, et al. Obstet Gynecol. 1997
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Basaloid SCC of Vulva
p16
p16 BerEP4 HPV-WS ISH
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Vulvar BCC
H&E
BerEP4p16
p16H&E
HPV-WS ISH
Elwood H, et al. Am J Surg Path, 2014
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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
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Primary EMPD Vulva
• 7th 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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Cam5.2
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CK903
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OverviewVulvovaginal 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 lesionsPaget’s disease of the breast
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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 sclerosingadenosis, columnar cell change, UDH, ADH, lactating adenoma
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Kazakov D, et al. Adv Anat Pathol, 2011
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OverviewVulvovaginal 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 lesionsPaget’s disease of the breast
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Verruciform Xanthoma
• Slow-growing, painless, solitary exophytictumors
• 0.5 to 2.0 cm in size• HPV has not been detected
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OverviewVulvovaginal 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 lesionsPaget’s disease of the breast
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Survey of 25 yrs JHH archivesCategory N=364 total
Soft tissue lesions (liposarcoma most common)
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
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• 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
Liposarcoma
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Localized Lymphedema
• Reactive, pseudotumor/pseudo-sarcoma
• Associated with obesity• Secondary to obstruction of lymphatic
flow
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OverviewVulvovaginal 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 lesionsPaget’s disease of the breast
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Paget’s disease of the nipple
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• 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
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Her2/neu
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• 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.
DDx: Toker cell hyperplasia
Garijo, MF, et al. Histol Histopathol, 2009
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CK7
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DDx: Pagetoid dyskeratosis
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CK903