Penis & scrotum

• Paget disease of the penis and scrotum is a rare, intraepidermal adenocarcinoma; it arises as a primary tumor or from secondary involvement of a nonpenoscrotal neoplasm

• Primary Paget disease: unknown precursor cell
  • May be Toker cell, as seen in other regions but not yet identified on penile or scrotal sites (Dermatol Online J 2019;25:13030)
  • May also originate from apocrine glands, eccrine glands or epidermal basal cells (Dermatol Online J 2019;25:13030)
• Secondary Paget disease: direct extension or epidermotropic spread of underlying tumor from urogenital, colorectal or cutaneous origin sites (Dis Colon Rectum 2019;62:1283)
  • Usually metachronous, with presentation at a median of 4 years after diagnosis of Paget disease (Dis Colon Rectum 2019;62:1283)

• No known risk factors
• Not human papillomavirus (HPV) related (Int J Surg Pathol 2018;26:617)
• 10% also have a genitourinary malignancy, most commonly prostatic adenocarcinoma, followed by urothelial carcinoma of the upper urinary tract / bladder (Dis Colon Rectum 2019;62:1283)

• Clinical history and evaluation with a punch biopsy (Dermatol Online J 2019;25:13030)
• Microscopic examination of tissue
• Clinical and radiologic evaluation in order to evaluate for secondary involvement from a tumor of nonpenoscrotal origin
• Sentinel lymph node biopsy may be considered to assist in disease staging (Dermatol Online J 2019;25:13030)

Images hosted on other servers:

AFIP images


Images hosted on other servers:

Contributed by Debra L. Zynger, M.D.

Contributed by Debra L. Zynger, M.D.

Contributed by Debra L. Zynger, M.D.

Images hosted on other servers:

• Primary (Dermatol Online J 2019;25:13030, Indian J Dermatol Venereol Leprol 2020;86:134, Hum Pathol 2016;47:70, Int J Surg Pathol 2018;26:617, Hum Pathol 2018;77:152, Appl Immunohistochem Mol Morphol 2020;28:524, Histopathology 2023;83:104)
  • AE1 / AE3, CAM 5.2, EMA, LMWK
  • CK7
  • CEA
  • GATA3
  • AR
  • TRPS1 (Histopathology 2023;83:104)
  • PAS, Alcian blue, colloidal iron, mucicarmine
  • GCDFP-15: variable expression in ~60 - 100% of cases
  • HER2: ~50% positive
• Secondary
  • Urothelial carcinoma: p63, CK5/6 (note: both express GATA3)
  • Prostatic adenocarcinoma: PSA, NKX3.1 (note: both express AR)
  • Colorectal adenocarcinoma: CK20 (note: both express CEA)

• Primary
  • p63, CK5/6
  • S100, HMB45, MelanA, SOX10
  • CK20, CDX2
  • NKX3.1, PSA, prostein
  • Vimentin
• Secondary
  • Urothelial carcinoma: CEA
  • Prostatic adenocarcinoma: CK7
  • Colorectal adenocarcinoma: CK7
• Reference: Appl Immunohistochem Mol Morphol 2020;28:524

A 68 year old man presented with a whitish, itchy plaque-like lesion that was located at the base of his penis and had grown larger over the past 2 years. The lesion was resected and a microscopic photo is shown above. Immunostains reveal that the lesional cells are positive for AE1 / AE3, CK7 and CEA and are negative for S100, CK20, CK5/6, p63 and NKX3.1. What is the diagnosis?

1. Malignant melanoma
2. Primary extramammary Paget disease
3. Prostatic adenocarcinoma
4. Squamous cell carcinoma
5. Urothelial carcinoma

B. Primary extramammary Paget disease. Penoscrotal extramammary Paget disease presents in elderly men as a whitish plaque. The lesion is often misdiagnosed for several years as a nonneoplastic lesion. Primary penoscrotal extramammary Paget disease tumoral cells express AE1 / AE3, CK7 and CEA and are negative for S100, CK20, CK5/6 and NKX3.1. Answer A is incorrect because melanoma is positive for S100 and negative for AE1 / AE3. Answer C is incorrect because prostatic adenocarcinoma is negative for CK7 and positive for NKX3.1. Answer D is incorrect because squamous cell carcinoma is negative for CEA and positive for p63 and CK5/6. Answer E is incorrect because urothelial carcinoma is positive for p63. Of note, primary penoscrotal extramammary Paget disease expresses GATA3 and AR, overlapping with urothelial carcinoma and prostatic adenocarcinoma.

Comment Here

Reference: Extramammary Paget disease

Which of the following markers is typically expressed in penoscrotal primary extramammary Paget disease (shown in the image)?

1. CK5/6
2. CK7
3. CK20
4. p63
5. S100

B. CK7 (shown in the image). Most cases of primary extramammary Paget disease express AE1 / AE3, EMA, CK7, CEA, GATA3 and AR. There is variable expression of GCDFP and HER2. Answers A, C, D and E are incorrect because most cases are negative for CK5/6, CK20, p63 and S100 and are also negative for CDX2, SOX10, HMB45, NKX3.1, PSA and prostein. Lack of expression for these makers helps exclude malignant melanoma, prostatic adenocarcinoma, squamous cell carcinoma and urothelial carcinoma.

Comment Here

Reference: Extramammary Paget disease