genital lesions in dermatopathology - pathcme.com · cutaneous lp. likeclassic hypertrophic lp...

Genital Lesions in Dermatopathology

Janis M. Taube, MDDirector of Dermatopathology

Associate Professor of Dermatology and PathologyJohns Hopkins University SOM

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

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

Spongiotic and PsorasiformPattern on Vulva

• Contact dermatitis• Psoriasis• Lichen simplex chronicus• Vulvovaginal candidiasis• Tinea infection• Extramammary Paget’s disease

• 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

•need strong clinical input to secure diagnosis of psoriasis at this site•biopsy is not necessary if clinically diagnosed unless lesion is treatment-resistant

DDx includes Paget’s disease (which may be subtle)

Beware!Erythematousvulvar eruptions that are:

•Therapy resistant•Eroded•Unilateral

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%)

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

Diagnosis: Primary, localized lichen amyloidosis of the vulva

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

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

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

Reported association of erosive LP and SCC is 2-3% of cases.

CK903

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)

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

• 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

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

HPV-WS ISH

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

Diffuse, block-like pattern in warty, basaloid SCC

Patchy, heterogeneous pattern in keratinizing SCC

P16 IHC and two types of vulvar SCC

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

Taube JM, Am J. Dermatopathol, 2011

Proposal for reclassification of VIN

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

Podophyllin-treatment reaction (most pronounced within 48-72 hours)

14/14 patients were immunocompromised: 13 had HIV and 1 was transplant patient

11/14 of cases

showed high-grade

VIN and condyloma

to be adjacent

H&E p16

HPV 6/11HPV 16

HSIL with condylomatous architecture

By ISH contained only HR-HPV, negative for HPV6/11

H&E p16

HPV-6/11

HPV-16

Right lateral perianal mass 39 y/o man

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

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

Basaloid SCC of Vulva

p16

p16 BerEP4 HPV-WS ISH

Vulvar BCC

H&E

BerEP4p16

p16H&E

HPV-WS ISH

Elwood H, et al. Am J Surg Path, 2014

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

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

Cam5.2

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

Kazakov D, et al. Adv Anat Pathol, 2011

Verruciform Xanthoma

• Slow-growing, painless, solitary exophytictumors

• 0.5 to 2.0 cm in size• HPV has not been detected

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

• 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

Localized Lymphedema

• Reactive, pseudotumor/pseudo-sarcoma

• Associated with obesity• Secondary to obstruction of lymphatic

flow

Paget’s disease of the nipple

• 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

Her2/neu

• 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

DDx: Pagetoid dyskeratosis

genital lesions in dermatopathology - pathcme.com · cutaneous lp. likeclassic hypertrophic lp...

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