Merkel cell polyomavirus is a passenger virus in both poroma and porocarcinoma.

BACKGROUND: Merkel cell polyomavirus (MCPyV) has been studied in several malignant and nonmalignant tissues. However, only in Merkel cell carcinoma (MCC) has the connection to tumorigenesis been established. Previously, eccrine porocarcinoma samples were shown to express MCPyV in the majority of samples. We aimed to examine MCPyV in porocarcinoma and poroma samples using MCC as the reference material. METHODS: We analyzed 17 porocarcinoma and 50 poroma samples for the presence of MCPyV using LT antigen immunostaining and DNA detection methods. In addition, 180 MCC samples served as controls. RESULTS: MCPyV LT antigen immunostaining was detected in 10% of poroma and 18% of porocarcinoma samples; on the other hand, it was present in 65% of MCC samples. MCPyV DNA was detected in only 10% of poroma and porocarcinoma samples compared with 96% of MCC samples. The viral DNA copy number in all MCPyV DNA-positive MCCs was at least 25 times higher than that in porocarcinoma or poroma samples with the highest MCPyV DNA-to-PTPRG ratio. CONCLUSIONS: The low number of viral DNA copies in poroma and porocarcinoma samples, together with the negative LT expression of MCPyV DNA-positive tumors, indicates that MCPyV is simply a passenger virus rather than an oncogenic driver of porocarcinoma.

Comparison of Immunohistochemical Expression of Cytokeratin 19, c-KIT, BerEP4, GATA3, and NUTM1 Between Porocarcinoma and Squamous Cell Carcinoma.

ABSTRACT: Distinguishing porocarcinoma from squamous cell carcinoma (SCC) is clinically significant; however, differential diagnosis can often be challenging. This study sought to confirm the diagnostic utility of cytokeratin 19, c-KIT, BerEP4, GATA3, and NUTM1 immunohistochemistry in distinguishing porocarcinoma from SCC. Immunohistochemical analysis of cytokeratin 19, c-KIT, BerEP4, GATA3, and NUTM1 in 14 porocarcinomas and 22 SCCs was performed; the extents and intensities of expression of these markers were recorded. The statistical associations of the immunoexpression between porocarcinoma and SCC were analyzed using the Pearson χ2 test. Cytokeratin 19 was positive in 13 (92.9%) of 14 porocarcinomas, and for all the positive cases, staining was strong and evident in >20% of the tumor cells. By contrast, 9 (40.9%) of 22 SCCs expressed cytokeratin 19 (P = 0.0018), of which 6 showed extremely focal (≤10% of the tumor cells) expression. Of the 14 porocarcinomas, 11 (78.6%) cases showed c-KIT positivity, whereas only 3 of 22 SCCs (13.6%) expressed c-KIT focally (P = 0.0001). In addition, BerEP4 immunostaining differed between porocarcinomas and SCCs (57.1% vs. 9.1%, respectively; P = 0.0017). However, no significant difference between the groups was reported in terms of GATA3 expression (57.1% vs. 72.7%, respectively; P = 0.3336). NUTM1 was expressed in 4/14 (28.6%) porocarcinomas but not in the SCCs. Immunohistochemistry for cytokeratin 19, c-KIT, and BerEP4 could be helpful in distinguishing porocarcinomas from SCCs. In addition, NUTM1 immunoexpression is highly specific, although not sensitive, to porocarcinomas. GATA3 immunohistochemistry has no meaningful implications in the differential diagnosis of porocarcinoma and SCC.

NUT Is a Specific Immunohistochemical Marker for the Diagnosis of YAP1-NUTM1-rearranged Cutaneous Poroid Neoplasms.

YAP1-NUTM1 fusion transcripts have been recently reported in poroma and porocarcinoma. NUTM1 translocation can be screened by nuclear protein in testis (NUT) immunohistochemistry in various malignancies, but its diagnostic performance has not been thoroughly validated on a large cohort of cutaneous epithelial neoplasms. We have evaluated NUT immunohistochemical expression in a large cohort encompassing 835 cases of various cutaneous epidermal or adnexal epithelial neoplasms. NUT expression was specific to eccrine poromas and porocarcinoma, with 32% of cases showing NUT expression. All other cutaneous tumors tested lacked NUT expression, including mimickers such as seborrheic keratosis, Bowen disease, basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, nodular hidradenoma, and all other adnexal tumors tested. Remarkably, NUT expression was more frequent in a distinct morphologic subgroup. Indeed, 93% of poroid hidradenoma (dermal/subcutaneous nodular poroma, 13/14) and 80% of poroid hidradenocarcinoma cases (malignant poroid hidradenoma, 4/5) showed NUT expression, in contrast to 17% and 11% of classic poroma (4/23) and porocarcinoma cases (4/35), respectively. RNA sequencing of 12 NUT-positive neoplasms further confirmed the presence of a YAP1-NUTM1 fusion transcript in all cases, and also an EMC7-NUTM1 gene fusion in a single case. In the setting of a cutaneous adnexal neoplasm, nuclear expression of NUT accurately and specifically diagnosed a specific subgroup of benign and malignant poroid tumors, all associated with a NUTM1 fusion, which frequently harbored a poroid hidradenoma morphology.

Utility of YAP1 and NUT immunohistochemistry in the diagnosis of porocarcinoma.

BACKGROUND: Porocarcinoma is the malignant counterpart of poroma, a benign tumor derived from the eccrine or apocrine units. In contrast to poroma, porocarcinoma is rare and its diagnosis may be challenging. Recent work has identified YAP1-associated gene fusions in most poromas, and a subset of porocarcinomas. These included YAP1-MAML2 and YAP1-NUTM1, the latter being enriched in porocarcinomas over poromas. METHODS: We studied YAP1 C-terminus and NUT immunohistochemistry in a cohort of 12 porocarcinomas, 10 poromas, 10 squamous cell carcinomas, and 6 hidradenocarcinomas. RESULTS: Seven of 12 (58%) porocarcinomas showed loss of YAP1 C-terminus expression, consistent with a YAP1 fusion. Of these seven, five showed NUT positivity, implying the presence of the YAP1-NUTM1 fusion. One of 12 (8%) cases showed NUT positivity, but retention of YAP1 C-terminus expression, consistent with a non-YAP1 NUT-associated fusion. Eight of 10 (80%) poromas showed loss of YAP1 C-terminus expression and negative NUT staining, consistent with non-NUT YAP1 fusions. All squamous cell carcinomas and hidradenocarcinomas retained YAP1 C-terminus expression and were negative for NUT. CONCLUSION: YAP1 C-terminus and NUT immunohistochemistry may be helpful in the diagnosis of porocarcinoma, with the combination of YAP1 C-terminus loss and NUT positivity being particularly informative.

Engrailed Homeobox 1 and Cytokeratin 19 Are Independent Diagnostic Markers of Eccrine Porocarcinoma and Distinguish It From Squamous Cell Carcinoma.

OBJECTIVES: The diagnostic utility of En1 in the histopathologic differentiation of eccrine porocarcinoma (EPC) from invasive squamous cell carcinoma (SCC) was investigated. METHODS: Expression of En1 and CK19 in 16 cases of EPC was immunohistochemically examined and compared with that in 32 cases of SCC. RESULTS: In all 16 EPCs, En1 was expressed in 3% to 100% of tumor cells. In 20 of the 32 SCCs, En1 was expressed in 3% to 90% of tumor cells. A total of 13 of the 16 EPCs and five of the 32 SCCs were judged as En1 positive, with a cutoff value of 25%. In addition, 11 of the 16 EPCs and four of the 32 SCCs were CK19 positive. The frequencies of En1- and CK19-positive cases were significantly higher in EPCs than in SCCs. In a logistic regression analysis for predicting EPC, En1 and CK19 were independent markers. When expression patterns of En1 and CK19 were combined, none of the 32 SCCs was both positive. In contrast, 15 of the 16 EPCs were positive for either En1 or CK19. CONCLUSIONS: A combination of En1 and CK19 expression can improve the accuracy of histologic diagnosis of EPC.

Altered Rb, p16, and p53 expression is specific for porocarcinoma relative to poroma.

BACKGROUND: Porocarcinomas are rare aggressive carcinomas that harbor tumor suppressor mutations and must be distinguished from benign entities such as poromas. METHODS: To determine whether altered expression of these genes was diagnostically informative, we examined p53, Rb, and p16 staining patterns in 15 poromas and 16 porocarcinomas. RESULTS: Poromas consistently displayed diffuse strong expression of Rb in all but one case that displayed focal loss (1/15, 7%), and no evidence of aberrancy in p53 or p16. Porocarcinomas displayed diffuse or focal loss of Rb expression in 9/16 (56%) cases, diffuse loss or overexpression of p53 in 8/15 (53%), and diffuse loss or overexpression of p16 in 6/14 (43%). Diffuse aberrancy in p53 and Rb expression correlated with tumor mutations in TP53 and RB1, respectively, whereas focal Rb loss was associated with wild type RB1. Diffuse p16 overexpression correlated with Rb loss rather than CDKN2A mutation. For porocarcinomas with all three stains evaluable, 10/13 (77%) displayed aberrancy in at least one marker. CONCLUSIONS: Our findings suggest that altered p53, p16, and/or Rb expression is relatively specific to porocarcinoma in comparison with poroma. Technical limitations of this panel, including possible focal Rb loss, must be kept in mind, especially in limited samples.

CD117 (KIT) is a useful immunohistochemical marker for differentiating porocarcinoma from squamous cell carcinoma.

BACKGROUND: Distinguishing porocarcinoma from squamous cell carcinoma (SCC) is clinically significant but can pose a diagnostic dilemma. The present study sought to confirm the diagnostic utility of CD117 immunohistochemistry in distinguishing porocarcinoma from SCC and to examine histologic, carcinoembryonic antigen (CEA) immunohistochemical and CA19-9 immunohistochemical differences between these tumors. METHODS: Immunostaining with anti-CD117, anti-CEA and anti-CA19-9 antibodies was performed for 22 porocarcinomas and 31 SCCs. The extent of CD117, CEA and CA19-9 staining was classified as negative (<1%), rarely positive (1-4%), focally positive (5-29%) or diffusely positive (30-100%). CD117 staining intensity was semi-quantitatively graded as weak, moderate or strong. RESULTS: All (100%) porocarcinomas were positive for CD117, with mainly focal (8/22) or diffuse (11/22) and moderate (9/22) to strong (8/22) staining. In contrast, only 6 of 31 SCCs (19.4%) expressed CD117 focally, and this expression was limited to the basal layer of the tumor in four cases. CEA immunostaining highlighted the lumina of all 22 porocarcinomas; however, CEA expression was not significantly different between porocarcinomas and SCCs (100 vs. 71.0%, respectively). CA19-9 was not expressed in the lumina of 5 of 22 porocarcinomas. CONCLUSIONS: Along with CEA, CD117 immunohistochemistry could be helpful in distinguishing porocarcinomas from SCCs.

A Rare Case of Eccrine Porocarcinoma of the Eyelid.

BACKGROUND: To report a rare case of eyelid eccrine porocarcinoma and compare this to previous documented cases in the literature. MAIN OBSERVATIONS: We report a case of an 86-year-old man who presented with three months' history of irritation in the right eye, who was found to have an irregular nodule on lower eyelid, which was later diagnosed as eccrine porocarcinoma (EPC). The lesion was excised and the defect repaired with Hughes flap. A computerized tomography (CT) scan of the head, neck, and chest showed no metastasis and no lymphadenopathy. There was no evidence of recurrence after 18 months of follow-up. CONCLUSION: To date, there have been only six cases of eyelid EPC reported in the literature. EPC has significant risk of recurrence and metastases after local excision. It is therefore important to consider it in the differential diagnosis of malignant eyelid tumour. A histological diagnosis should prompt wide margin excision, assessment of the patient for regional lymph node involvement, and imaging for metastatic disease.

Perilipin and adipophilin expression in sebaceous carcinoma and mimics.

Although adipophilin has been reported to be a sensitive marker for sebaceous carcinoma, others have noted its expression in squamous cell carcinoma and a variety of noncutaneous tumors, suggesting that lipid droplet accumulation is a frequent feature of neoplastic cells. We investigated the expression of adipophilin and perilipin in 101 cutaneous carcinomas. They included 30 cases of sebaceous carcinoma, 28 squamous cell carcinoma with clear cell change (18 invasive and 10 in situ tumors), 8 hidradenocarcinomas, 1 spiradenocarcinoma, 10 porocarcinomas, 4 malignant chondroid syringomas, 1 malignant cylindroma, 7 apocrine carcinomas, 6 eccrine carcinomas, 5 aggressive digital papillary adenocarcinomas, and 1 pilomatrical carcinoma. Adipophilin stained the rim of cytoplasmic lipid droplets in various tumor types, including sebaceous carcinomas (30/30, 100%), squamous cell carcinoma with clear cell change (21/28, 75%), and eccrine-apocrine carcinomas (25/43, 58%). On the other hand, perilipin expression was seen in 13 (43%) of 30 sebaceous carcinoma and only 1 hidradenocarcinoma. The remaining 28 squamous cell carcinomas with clear cell change and 42 eccrine-apocrine carcinomas were negative. Although specific for invasive sebaceous carcinoma, perilipin expression was not helpful in distinguishing sebaceous carcinoma in situ from squamous cell carcinoma in situ with clear cell change. The expression of adipophilin seen in variety of cutaneous tumors suggests that the biosynthesis of lipid is altered in these neoplasms.

BerEP4 is widely expressed in tumors of the sweat apparatus: a source of potential diagnostic error.

BACKGROUND: A 63-year-old man presented with an ulcerated nodule with a rolled pearly edge on his back. A punch biopsy showed diffuse strong BerEP4 expression and retraction artifact. Consequently the tumor was diagnosed as a basal cell carcinoma but on excision the tumor proved to be a porocarcinoma. Although Jimenez et al. reported BerEP4 expression in porocarcinoma, this result is not widely appreciated. This observation prompted us to investigate BerEP4 expression in sweat apparatus tumors. METHODS: Immunocytochemistry was performed using Dako monoclonal mouse BerEP4 with Ventana Benchmark XT immunostainer. Omission of the primary antibody served as a negative control. RESULTS: Fourteen of 26 porocarcinomas had at least focal BerEP4 expression and two were diffusely and at least focally strongly positive. Seven of seven chondroid syringomas stained diffusely positive, with strong ductal expression; the single chondroid syringocarcinoma was negative. Five of 6 poromas and two of two hidradenomas had focal expression, and staining particularly highlighted the ducts, a co-localization also apparent in the four spiradenomas and three cylindromas. The single primary mucinous carcinoma had diffuse strong BerEP4 expression. DISCUSSION: This case and pilot study shows that BerEP4 expression is common in these selected sweat apparatus tumors, and staining may be strongly so. This observation should be borne in mind in clinical practice.

An immunohistochemical comparison of cytokeratin 7, cytokeratin 15, cytokeratin 19, CAM 5.2, carcinoembryonic antigen, and nestin in differentiating porocarcinoma from squamous cell carcinoma.

The distinction of porocarcinoma from squamous cell carcinoma is clinically relevant but can often be a diagnostic dilemma. Current markers reported to be helpful in diagnosing porocarcinoma include carcinoembryonic antigen and cytokeratin 7; however, their expression has been demonstrated in 30% to 80% and 13% to 22% of squamous cell carcinoma cases, respectively. In this study, we assessed immunohistochemical expression of cytokeratin 7, cytokeratin 15, cytokeratin 19, CAM 5.2, carcinoembryonic antigen, and nestin in 67 cases (39 porocarcinomas and 28 moderately differentiated squamous cell carcinomas) to determine their use as histologic adjuncts. Expression of carcinoembryonic antigen, cytokeratin 19, cytokeratin 7, CAM 5.2, cytokeratin 15, and nestin was seen in 77%, 67%, 64%, 51%, 49%, and 13% of porocarcinomas, respectively; and in 57%, 18%, 26%, 32%, 30%, and 37% of squamous cell carcinomas, respectively. Of these, cytokeratin 19 was the most specific (specificity, 82%) in detecting porocarcinomas, and carcinoembryonic antigen was the most sensitive (sensitivity, 77%). By χ(2) test, statistically significant P values (<.05) were observed for cytokeratin 7, cytokeratin 19, and nestin in the distinction of porocarcinoma from squamous cell carcinoma. However, in a logistic regression and stepwise selection for predicting a porocarcinoma, statistical significance was observed only for cytokeratin 19 (P = .0003). In conclusion, we found cytokeratin 19 to be a helpful marker in the distinction of porocarcinoma from squamous cell carcinoma, although a focal staining pattern can be seen in a third of cases. The diagnostic sensitivity and specificity appear to be significantly improved using a selected panel of immunohistochemical stains that include cytokeratin 7, cytokeratin 19, and nestin.

A case of porocarcinoma arising in pigmented hidroacanthoma simplex with multiple lymph node, liver and bone metastases.

Porocarcinoma is a rare skin appendage carcinoma that may arise de novo or be associated with pre-existing poroma and hidroacanthoma simplex (HAS). Here, we report a case of porocarcinoma arising in pigmented HAS, which led to death from multiple lymph node, liver and bone metastases. A 72-year-old Japanese man presented with a brown to focal black flat plaque, measuring 17 × 12 mm, on the posterior region of his right thigh. Histopathological study of the tumor revealed that there was intraepidermal proliferation of small-sized basaloid cells, and it exhibited the 'Jadassohn phenomenon', with dendritic melanocytes, and a few ductal structures were observed. Continuing to the intraepidermal nests, the invasive proliferation of large polygonal cells with occasional intracytoplasmic ductal structures was observed. Carcinoembryonic antigen and epithelial membrane antigen were expressed in some carcinoma cells and they highlighted the intracytoplasmic ductal structures. Multiple lymph node, liver and bone metastases were observed, and the patient died 8 months after the initial surgery. Clinical diagnosis of HAS is extremely rare. Porocarcinoma may be associated with pre-existing HAS and sometimes shows aggressive behavior. Therefore, pigmented HAS must be included in the differential diagnosis of brown or black lesions. Ishida M, Hotta M, Kushima R, Okabe H. A case of porocarcinoma arising in pigmented hidroacanthoma simplex with multiple lymph node, liver and bone metastases.