extramammary Paget disease

Images

 Extramammary Paget disease.

• https://twitter.com/JMGardnerMD/status/674200848369475585
• https://twitter.com/JRamirezMD/status/881860527684767746

Digital cases

 JRC:10823 : Extramammary Paget disease.

Localization

 cutaneous Paget disease
 vulvar Paget disease
 extramammary Paget disease in a retrorectal dermoid cyst (18367943)

IHC

Primary extramammary Paget’s disease is positive for CEA, CK7, CAM 5.2, GCDFP-15, Her2-neu, EMA and infrequently CK20.

Differential diagnosis

 urothelial carcinoma

• IHC: positive for CK7, CK20 and uroplakin.

 primary anorectal adenocarcinoma

• IHC : CK20 +, CK7 -, CDX2 +, MUC2 +.

Differential diagnosis

 clear cell papulosis
 metastatic epidermotropic carcinoma
 melanocytic lesions
 Pagetoid actinic keratosis
 Pagetoid Bowen disease

Molecular biology

The mutations of MLH1 V384D (15.7%), R217C (4.1%), and I219V (5.2%) are common in this cancer. (27487738)

In a study, the yeast 2-hybrid and immunoprecipitation assays exhibited reduced interaction between MLH1 and PMS2 in MLH1 V384D and R217C but not I219V. (27487738)

Moreover, MLH1 V384D and R217C had impaired MMR activity compared with the wild-type and I219V mutation by an in vitro MMR assay. (27487738)

The germline mutations in MMR genes are involved in the pathogenesis of EMPD and partially explain the genetic abnormalities for this disease.

References

 Thway K, Polson A, Pope R, Thomas JM, Fisher C. Extramammary Paget Disease in a Retrorectal Dermoid Cyst: Report of a Unique Case. Am J Surg Pathol. 2008 Apr;32(4):635-639. PMID: 18367943