Porocarcinoma: Clinical and Histological Features, Immunohistochemistry and Outcomes: A Systematic Review.

Porocarcinoma (PC) is a rare adnexal tumor, mainly found in the elderly. The tumor arises from the acrosyringium of eccrine sweat glands. The risk of lymph node and distant metastasis is high. Differential diagnosis with squamous cell carcinoma is difficult, although NUT expression and YAP1 fusion products can be very useful for diagnosis. Currently, wide local excision is the main surgical treatment, although Mohs micrographic surgery is promising. To date, there is no consensus regarding the role of sentinel lymph node biopsy and consequential lymph node dissection. No guidelines exist for radiotherapy, which is mostly performed based on tumor characteristics and excision margins. Only a few studies report systemic treatment for advanced PC, although therapy with pembrolizumab and EGFR inhibitors show promise. In this review, we discuss epidemiology, clinical features, histopathological features, immunohistochemistry and fusion products, surgical management and survival outcomes according to stage, surgical management, radiotherapy and systemic therapy.

Porocarcinoma with YAP1-NUTM1 fusion presenting as a NUT immunohistochemistry-positive lymph node metastasis.

INTRODUCTION: Porocarcinoma is a rare, malignant adnexal tumor that recently has been shown to contain YAP1-NUTM1 and YAP1-MAML2 fusion transcripts, with nuclear protein in testis (NUT) immunohistochemistry (IHC) positivity in a subset of these tumors. Consequently, NUT IHC may either aid in the differential diagnosis, or represent a confounding factor depending on the clinical scenario. Here, we present a case of NUTM1-rearranged sarcomatoid porocarcinoma of the scalp presenting as a NUT IHC-positive lymph node metastasis. CASE REPORT: A mass was excised from the right neck level 2 region with a lymph node initially diagnosed as metastatic NUT carcinoma with unknown primary site. An enlarging scalp mass was identified 4 months later, excised and diagnosed as NUT-positive carcinoma. Additional molecular testing was performed to detect the fusion partner in the NUTM1 rearrangement, confirming a YAP1-NUTM1 fusion. Given this molecular data along with the histopathologic characteristics, the clinicopathologic picture was retrospectively determined to be most consistent with a primary sarcomatoid porocarcinoma of the scalp with metastasis to a right neck lymph node and the right parotid. DISCUSSION: Porocarcinoma is a rare entity, and typically only enters the differential diagnosis when the clinical consideration is a cutaneous neoplasm. In an alternative clinical scenario such as the approach to tumors of the head and neck, porocarcinoma is not typically a consideration. In the latter scenario, as seen in our case, positivity with NUT IHC led to the initial misdiagnosis of NUT carcinoma. This case represents an important presentation of porocarcinoma that will occur not infrequently, and pathologists must be aware of this presentation to avoid this pitfall.

Porocarcinoma: a review.

From the first report in 1969 to the present day, diagnosis of eccrine porocarcinoma, also known simply as porocarcinoma (PC), remains a challenge. This review presents a concise update of the history, pathogenesis, epidemiology, diagnosis, management and prognosis of this rare sweat gland neoplasm. PC differentiates towards the intraepidermal spiral ducts in the eccrine gland, is more common in people aged > 60 years and often affects the head, neck and legs. PC presents as a dome-shaped papule, plaque or nodule growing over weeks to months. The exact incidence of PC is unknown but appears to be rising. Diagnosis is difficult because of variable presentations and similar clinical and histological features to cutaneous squamous cell carcinoma. Management involves removal of the tumour, usually using wide local excision or Mohs micrographic surgery. Prognosis is poor, with PC recurring after surgery in 35% of cases. Given the lack of standardized protocols and risk profiles, further studies would help improve the understanding of PC.

Poroid adnexal skin tumors with YAP1 fusions exhibit similar histopathologic features: A series of six YAP1-rearranged adnexal skin tumors.

BACKGROUND: Adnexal skin tumors are diagnostically challenging with few known molecular signatures. Recently, however, YAP1-MAML2 and YAP1-NUTM1 fusions were identified in poroid adnexal skin tumors. METHODS: Herein, we subjected eight poroid adnexal skin tumors (three poromas and five porocarcinomas) to fusion gene analysis by whole transcriptome sequencing and next-generation DNA sequencing analysis. RESULTS: YAP1 fusions were identified in six cases. YAP1-NUTM1 fusions were identified in two poromas and three porocarcinomas. A single case of porocarcinoma harbored a YAP1-MAML2 fusion. Two cases were negative for gene fusion. All cases that harbored YAP1-NUTM1 fusions showed nuclear protein in testis (NUT) expression by immunohistochemistry, with NUT being negative in the YAP1-MAML2-positive case. In this case series, we provide a detailed histopathologic description of six YAP1-fused poroid skin tumors, which we show harbor reproducible histopathologic features, to include broad, bulbous tumor tongues with admixtures of basaloid, poroid cells punctuated by squamatized cuticles and ductules, with uniform tumor nuclei featuring frequent grooves and pseudonuclear inclusions. CONCLUSIONS: Awareness of the characteristic histopathologic features of YAP1-fused poroid adnexal skin tumor is a step toward a more reproducible classification of adnexal skin tumors as well as a step toward targeted therapy for metastatic and/or unresectable examples of this poroid group of neoplasms.

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.

Malignant Eccrine Porocarcinoma in Finland During 2007 to 2017.

Malignant eccrine porocarcinoma is a rare skin adnexal cancer arising from the sweat glands. Little is known about the epidemiology and incidence of eccrine porocarcinoma. This registry-based study examined the epidemiology and incidence data for eccrine porocarcinoma from the Finnish Cancer Registry. The study included all persons diagnosed with eccrine porocarcinoma in 2007 to 2017. There were 69 cases in the study period; 34 (49%) male and 35 (51%) female patients. Mean age at diagnosis was 75.5 years. Incidence for men was 0.06 per 100,000 person-years and for women 0.04 per 100,000 person-years adjusted for age according to the World Standard Population. Incidence increased with age. There was one eccrine porocarcinoma-specific death among the 69 patients. The incidence of eccrine porocarcinoma in Finland is therefore low. The mean age at time of diagnosis and the location of eccrine porocarcinoma are consistent with previous reports. The survival of patients with eccrine porocarcinoma is high.

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.

Basal Cell Carcinoma and Eccrine Porocarcinoma of the Eyelid.

An 81-year-old woman presented with a progressively enlarging indurated, firm lesion encompassing one-third of the left upper eyelid. Four years prior, a similar lesion at that same site had been excised and diagnosed as a basal cell carcinoma. The patient underwent a full-thickness excision of the lesion with frozen section, cryotherapy, and reconstruction. A free tarsal graft and hard palate composite graft was used to reconstruct the posterior lamella. A Mustarde myocutaneous rotational flap was used to reconstruct the anterior lamella. Histopathology illustrated nests of pleomorphic basophilic cells with varying mitotic activity and immunohistochemical staining consistent with eccrine porocarcinoma. This case highlights similarities in the presentation and appearance of basal cell carcinoma and periorbital eccrine porocarcinoma. It is possible that there was de novo development of the 2 tumors on the eyelid or recurrence of a misdiagnosed eccrine porocarcinoma. Eccrine porocarcinomas are rare malignant sweat gland tumors associated with a risk of recurrence after excision and metastasis.

Vulval hidradenoma papilliferum: a clinical and dermoscopic study.

Hidradenoma papilliferum (HP) is a rare, slow-growing, benign adnexal tumour with apocrine differentiation. It usually affects the anogenital region in adult women and is clinically polymorphous, mimicking other benign or malignant neoformations. The dermoscopic features of vulval HP have not been reported yet. We report the clinical and dermoscopic features in a case series of histopathologically proven vulval HPs. Dermoscopy may be a useful tool for the diagnosis of vulval HP. To our knowledge, our paper represents the first report of dermoscopic findings in a series of vulval HPs in a multiracial population.

Eccrine Porocarcinoma: A Rare Tumor of the Eyelid With a Novel Histopathological Finding of Free Tumor Cells in the Tear Film.

The authors present a case of an eyelid eccrine porocarcinoma, a very rare malignant sweat gland tumor characterized histopathologically by nests of atypical poromatous cells and the presence of duct-like lumina. Histopathologic analysis of this case also exhibited numerous loose tumor cells in the adjacent tear film, a finding that has not been previously described.

Eccrine Porocarcinoma: New Insights and a Systematic Review of the Literature.

BACKGROUND: Eccrine porocarcinoma (EPC) is a rare cutaneous neoplasm with high potential for morbidity and mortality. Due to its rarity, there is a paucity of data profiling diagnosis, work-up, and management. OBJECTIVE: To consolidate reported information on demographics, diagnostics, clinical behavior, treatment modalities, and patient outcomes in EPC to provide a reference tool to optimize diagnosis and management. METHODS: A comprehensive PubMed search was performed from 1963 to November 2017 using PRISMA guidelines. This yielded 155 articles detailing 206 cases of porocarcinoma. RESULTS: Eccrine porocarcinoma most often presents in elderly patients on the head and neck or lower limbs. Metastatic disease at presentation is not uncommon (22%). Primary tumor location is significantly correlated with presence of metastasis (p = .038). The most common treatment is excision followed by Mohs micrographic surgery (MMS), although the outcomes after MMS were superior to those after surgical excision. CONCLUSION: This systematic review of individual patient data reveals that all patients should have a histological diagnosis with imaging considered for high-risk cases. Primary tumor location should also be considered in diagnostic and therapeutic decision-making. Although wide local excision (WLE) is currently the first-line treatment, MMS is becoming increasingly used, with evidence indicating improved outcomes as compared to those seen with WLE.

Eccrine Porocarcinoma: Patient Characteristics, Clinical and Histopathologic Features, and Treatment in 7 Cases. / Porocarcinoma ecrino: aspectos demográficos, clínicos, histopatológicos y terapéuticos en una serie de 7 pacientes.

Eccrine porocarcinoma is a rare, malignant cutaneous adnexal tumor that arises from the ducts of sweat glands. Found mainly in patients of advanced age, this tumor has diverse clinical presentations. Histology confirms the diagnosis, detects features relevant to prognosis, and guides treatment. Growth is slow, but the prognosis is poor if the tumor metastasizes to lymph nodes or visceral organs. We report 7 cases of eccrine porocarcinoma, describing patient characteristics, the clinical and histopathologic features of the tumors, and treatments used. Our observations were similar to those of other published case series. Given the lack of therapeutic algorithms or protocols for this carcinoma, we propose a decision-making schema based on our review of the literature and our experience with this case series. The algorithm centers on sentinel lymph node biopsy and histologic features.

Subcutaneous porocarcinoma clinically presenting as a soft tissue tumor.

Porocarcinoma is a rare malignancy with glandular adnexal differentiation. A 38-year-old Japanese man noticed a subcutaneous mass in right inguinal region about 20 years prior to being examined. Radiological examinations demonstrated the mass, 11 × 10 cm in size, was in the subcutaneous fat tissue. Recently, the mass grew rapidly, and it was biopsied by an orthopedist based on clinical diagnosis of primary soft tissue tumor. Histopathological examination of the resected specimens also revealed that the tumor lacked involvement to the skin. Microscopically, the tumor was mainly composed of poroid cells with partially obvious squamous differentiation, accompanied by focal ductal structures immunoreactive for CEA and EMA. The tumor contained a low-grade area consisting of poroid cells and high-grade area with squamous differentiation. This histopathological heterogeneity suggested malignant transformation from poroma. The patient had the tumor in almost same size over the period of 20 years, which is the longest in the previous reports. This unique case of subcutaneous porocarcinoma is reported.