SOX10-Internal Tandem Duplications and PLAG1 or HMGA2 Fusions Segregate Eccrine-Type and Apocrine-Type Cutaneous Mixed Tumors.

Cutaneous mixed tumors exhibit a wide morphologic diversity and are currently classified into apocrine and eccrine types based on their morphologic differentiation. Some cases of apocrine-type cutaneous mixed tumors (ACMT), namely, hyaline cell-rich apocrine cutaneous mixed tumors (HCR-ACMT) show a prominent or exclusive plasmacytoid myoepithelial component. Although recurrent fusions of PLAG1 have been observed in ACMT, the oncogenic driver of eccrine-type cutaneous mixed tumors (ECMT) is still unknown. The aim of the study was to provide a comprehensive morphologic, immunohistochemical, and molecular characterization of these tumors. Forty-one cases were included in this study: 28 cases of ACMT/HCR-ACMT and 13 cases of ECMT. After morphologic and immunohistochemical characterization, all specimens were analyzed by RNA sequencing. By immunohistochemistry, all cases showed expression of SOX10, but only ACMT/HCR-ACMT showed expression of PLAG1 and HMGA2. RNA sequencing confirmed the presence of recurrent fusion of PLAG1 or HMGA2 in all cases of ACMT/HCR-ACMT, with a perfect correlation with PLAG1/HMGA2 immunohistochemical status, and revealed internal tandem duplications of SOX10 (SOX10-ITD) in all cases of ECMT. Although TRPS1::PLAG1 was the most frequent fusion, HMGA2::WIF1 and HMGA2::NFIB were detected in ACMT cases. Clustering analysis based on gene expression profiling of 110 tumors, including numerous histotypes, showed that ECMT formed a distinct group compared with all other tumors. ACMT, HCR-ACMT, and salivary gland pleomorphic adenoma clustered together, whereas myoepithelioma with fusions of EWSR1, FUS, PBX1, PBX3, POU5F1, and KLF17 formed another cluster. Follow-up showed no evidence of disease in 23 cases across all 3 tumor types. In conclusion, our study demonstrated for the first time SOX10-ITD in ECMT and HMGA2 fusions in ACMT and further refined the prevalence of PLAG1 fusions in ACMT. Clustering analyses revealed the transcriptomic distance between these different tumors, especially in the heterogenous group of myoepitheliomas.

Wnt/ß-Catenin-Activated Nonpilomatrical Carcinoma of the Skin: A Case Series.

Among skin epithelial tumors, recurrent mutations in the APC/CTNNB1 genes resulting in activation of the Wnt/ß-catenin pathway have been reported predominantly in neoplasms with matrical differentiation. In the present study, we describe the morphologic, immunohistochemical, and genetic features of 16 primary cutaneous carcinomas harboring mutations activating the Wnt/ß-catenin pathway without evidence of matrical differentiation, as well as 4 combined tumors in which a similar Wnt/ß-catenin-activated carcinoma component was associated with Merkel cell carcinoma (MCC) or pilomatrical carcinoma. Among the pure tumor cases, 6 of 16 patients were women with a median age of 80 years (range, 58-98 years). Tumors were located on the head and neck (n = 7, 44%), upper limb (n = 4, 25%), trunk (n = 3, 18%), and leg (n = 2, 13%). Metastatic spread was observed in 4 cases resulting in death from disease in 1 patient. Microscopically, all cases were poorly differentiated neoplasms infiltrating the dermis and/or subcutaneous tissue. In 13 cases, solid "squamoid" areas were associated with a basophilic component characterized by rosette/pseudoglandular formation resulting in a biphasic appearance. Three specimens consisted only of poorly differentiated carcinoma lacking rosette formation. Immunohistochemical studies showed frequent expression of EMA (100%), BerEP4 (100%), cytokeratin 7 (94%), chromogranin A (44%), synaptophysin (82%), and cytokeratin 20 (69%). Complete loss of Rb expression was observed in all but 1 case. Nuclear ß-catenin and CDX2 expressions were detected in all cases. Recurrent pathogenic somatic mutations were observed in APC (60%), CTNNB1 (40%), and RB1 (n = 47%). Global methylation analysis confirmed that cases with rosette formation constituted a homogeneous tumor group distinct from established skin tumor entities (pilomatrical carcinoma, MCC, and squamous cell carcinoma), although the 3 other cases lacking such morphologic features did not. In addition, we identified 4 combined neoplasms in which there was a component showing a similar poorly differentiated rosette-forming carcinoma demonstrating Rb loss and ß-catenin activation associated with either MCC (n = 3) or pilomatrical carcinoma (n = 1). In conclusion, we describe a distinctive neoplasm, for which we propose the term "Wnt/ß-catenin-activated rosette-forming carcinoma," morphologically characterized by the association of rosette formation, squamous and/or neuroendocrine differentiation, diffuse CDX2 expression, Rb loss, and mutations in CTNNB1/APC genes.

Gene fusions in poroma, porocarcinoma and related adnexal skin tumours: An update.

Poroma is a benign sweat gland tumour showing morphological features recapitulating the superficial portion of the eccrine sweat coil. A subset of poromas may transform into porocarcinoma, its malignant counterpart. Poroma and porocarcinoma are characterised by recurrent gene fusions involving YAP1, a transcriptional co-activator, which is controlled by the Hippo signalling pathway. The fusion genes frequently involve MAML2 and NUTM1, which are also rearranged in other cutaneous and extracutaneous neoplasms. We aimed to review the clinical, morphological and molecular features of this category of adnexal neoplasms with a special focus upon emerging differential diagnoses, and discuss how their systematic molecular characterisation may contribute to a standardisation of diagnosis, more accurate classification and, ultimately, refinement of their prognosis and therapeutic modalities.

Porocarcinomas with PAK1/2/3 fusions: a series of 12 cases.

AIMS: Porocarcinoma is a malignant sweat gland tumour differentiated toward the upper part of the sweat duct and may arise from the transformation of a preexisting benign poroma. In 2019, Sekine et al. demonstrated the presence of YAP1::MAML2 and YAP1::NUTM1 fusions in most poromas and porocarcinomas. Recently, our group identified PAK2-fusions in a subset of benign poromas. Herein we report a series of 12 porocarcinoma cases harbouring PAK1/2/3 fusions. METHODS AND RESULTS: Five patients were male and the median age was 79 years (ranges: 59-95). Tumours were located on the trunk (n = 7), on the thigh (n = 3), neck (n = 1), or groin area (n = 1). Four patients developed distant metastases. Microscopically, seven cases harboured a benign poroma component and a malignant invasive part. Ductal formations were observed in all, while infundibular/horn cysts and cells with vacuolated cytoplasm were detected in seven and six tumours, respectively. In three cases, the invasive component consisted of a proliferation of elongated cells, some of which formed pseudovascular spaces, whereas the others harboured a predominant solid or trabecular growth pattern. Immunohistochemical staining for CEA and EMA confirmed the presence of ducts. Focal androgen receptor expression was detected in three specimens. Whole RNA sequencing evidenced LAMTOR1::PAK1 (n = 2), ZDHHC5::PAK1 (n = 2), DLG1::PAK2, CTDSP1::PAK1, CTNND1::PAK1, SSR1::PAK3, CTNNA1::PAK2, RNF13::PAK2, ROBO1::PAK2, and CD47::PAK2. Activating mutation of HRAS (G13V, n = 3, G13R, n = 1, Q61L, n = 2) was present in six cases. CONCLUSION: Our study suggests that PAK1/2/3 fusions is the oncogenic driver of a subset of porocarcinomas lacking YAP1 rearrangement.

Radiotherapy and prognostic factors in adnexal carcinomas: A retrospective study of 657 patients from the French CARADERM network.

BACKGROUND: Cutaneous adnexal carcinomas are a heterogeneous group of rare neoplasms. Surgical excision is the first-line treatment in localized stage. The use and effectiveness of radiotherapy have not been thoroughly evaluated in these neoplasms. OBJECTIVES: The present work analyses prognostic factors on outcomes in skin adnexal carcinomas, based on data from the CARADERM (CAncers RAres DERMatologiques) database. METHODS: Data were collected retrospectively including demographic data, tumour types and therapeutic characteristics of all patients included in the CARADERM database, with at least one informative follow-up visit. Analyses were performed on three populations: patients with complete resection of the primary tumour (ADJ/primary population), patients achieving complete remission after complete resection of a recurrent tumour (ADJ/recurrent population) and patients with unresectable locally advanced or metastatic tumours (ADV/MET population). Overall and recurrence/progression-free survivals at 3-year were analysed using Cox regression models. RESULTS: Radiotherapy did not affect overall survival (OS) in the ADJ/primary population. Adjusted recurrence-free survival (RFS) was significantly lower in the radiotherapy group in ADJ/primary group. Older patients had significantly poorer OS and RFS. Tumour size and immunosuppression were significantly associated with poorer RFS only. Radiotherapy had no effect on OS and RFS in the ADJ/recurrent population. Age was the only factor associated with a poorer OS. Radiotherapy was significantly associated with longer progression-free survival (PFS) in age-sex adjusted analysis in the ADV/MET population, without effect on OS. CONCLUSIONS: Our study shows that age, tumour size and immunosuppression are significantly associated with survival in localized adnexal carcinomas. Radiotherapy may improve PFS in the ADV/MET population but not in localized and recurrent carcinomas after complete excision.

Recurrent PAK2 rearrangements in poroma with folliculo-sebaceous differentiation.

AIMS: Poroma is a benign adnexal neoplasm with differentiation towards the upper portion of the sweat gland apparatus. In 2019, Sekine et al. demonstrated recurrent YAP1::MAML2 and YAP1::NUTM1 fusion in poroma and porocarcinoma. Follicular, sebaceous and/or apocrine differentiation has been reported in rare cases of poroma and whether these tumours constitute a variant of poroma or represent a distinctive tumour is a matter to debate. Herein we describe the clinical, immunophenotypic, and molecular features of 13 cases of poroma with folliculo-sebaceous differentiation. METHODS AND RESULTS: Most of the tumours were located on the head and neck region (n = 7), and on the thigh (n = 3). All presented were adults with a slight male predilection. The median tumour size was 10 mm (range: 4-25). Microscopically, lesions displayed features of poroma with nodules of monotonous basophilic cells associated with a second population of larger eosinophilic cells. In all cases, ducts and scattered sebocytes were identified. Infundibular cysts were present in 10 cases. In two cases high mitotic activity was noted, and in three cases cytologic atypia and areas of necrosis were identified. Whole transcriptome RNA sequencing demonstrated in-frame fusion transcripts involving RNF13::PAK2 (n = 4), EPHB3::PAK2 (n = 2), DLG1::PAK2 (n = 2), LRIG1::PAK2 (n = 1), ATP1B3::PAK2 (n = 1), TM9SF4::PAK2 (n = 1), and CTNNA1::PAK2 (n = 1). Moreover, fluorescence in situ hybridisation (FISH) analysis revealed PAK2 rearrangement in an additional case. No YAP1::MAML2 or YAP1::NUTM1 fusion was detected. CONCLUSION: Recurrent fusions involving the PAK2 gene in all analysed poroma with folliculo-sebaceous differentiation in this study confirms that this neoplasm represents a separate tumour entity distinct from YAP1::MAML2 or YAP1::NUTM1 rearranged poromas.

Distinct regulations driving YAP1 expression loss in poroma, porocarcinoma and RB1-deficient skin carcinoma.

AIMS: Recently, YAP1 fusion genes have been demonstrated in eccrine poroma and porocarcinoma, and the diagnostic use of YAP1 immunohistochemistry has been highlighted in this setting. In other organs, loss of YAP1 expression can reflect YAP1 rearrangement or transcriptional repression, notably through RB1 inactivation. In this context, our objective was to re-evaluate the performance of YAP1 immunohistochemistry for the diagnosis of poroma and porocarcinoma. METHODS AND RESULTS: The expression of the C-terminal part of the YAP1 protein was evaluated by immunohistochemistry in 543 cutaneous epithelial tumours, including 27 poromas, 14 porocarcinomas and 502 other cutaneous tumours. Tumours that showed a lack of expression of YAP1 were further investigated for Rb by immunohistochemistry and for fusion transcripts by real-time PCR (YAP1::MAML2 and YAP1::NUTM1). The absence of YAP1 expression was observed in 24 cases of poroma (89%), 10 porocarcinoma (72%), 162 Merkel cell carcinoma (98%), 14 squamous cell carcinoma (SCC) (15%), one trichoblastoma and one sebaceoma. Fusions of YAP1 were detected in only 16 cases of poroma (n = 66%), 10 porocarcinoma (71%) all lacking YAP1 expression, and in one sebaceoma. The loss of Rb expression was detected in all cases except one of YAP1-deficient SCC (n = 14), such tumours showing significant morphological overlap with porocarcinoma. In-vitro experiments in HaCat cells showed that RB1 knockdown resulted in repression of YAP1 protein expression. CONCLUSION: In addition to gene fusion, we report that transcriptional repression of YAP1 can be observed in skin tumours with RB1 inactivation, including MCC and a subset of SCC.

Recurrent FOXK1::GRHL and GPS2::GRHL fusions in trichogerminoma.

We report 21 cases of trichogerminoma harbouring previously undescribed FOXK1::GRHL1/2 or GPS2::GRHL1/2/3 in-frame fusion transcripts. Microscopic examination of a preliminary set of five cases revealed well-delimitated tumours located in the dermis with frequent extension to the subcutaneous tissue. Tumours presented a massive and nodular architecture and consisted of a proliferation of basaloid cells. A biphasic pattern sometime resulting in tumour cell nests ('cell balls') was present. Immunohistochemistry demonstrated the expression of cytokeratins (CKs) 15, 17, and PHLDA1. In addition, numerous CK20-positive Merkel cells were detected. RNA sequencing (RNA-seq) revealed a FOXK1::GRHL1 chimeric transcript in three cases and a FOXK1::GRHL2 fusion in two cases. In a second series for validation (n = 88), FOXK1::GRHL1/2 fusion transcripts were detected by RT-qPCR or FISH in an additional 12 trichogerminomas and not in any other follicular tumour entities or basal cell carcinoma cases (n = 66). Additional RNA-seq analysis in trichogerminoma cases without detected FOXK1::GRHL1/2 rearrangements revealed GPS2::GRHL1 fusion transcripts in two cases, GPS2::GRHL2 in one case, and GPS2::GRHL3 fusion transcript in one case. Therefore, our study strongly suggests that GRHL1/2/3 gene rearrangements might represent the oncogenic driver in trichogerminoma, a subset of follicular tumours characterized by immature features and numerous Merkel cells. © 2022 The Pathological Society of Great Britain and Ireland.

Microsecretory adenocarcinoma of the skin, a novel type of sweat gland carcinoma: Report of three additional cases.

Microsecretory adenocarcinoma (MSA) is a newly described salivary gland tumor harboring a characteristic balanced chromosomal translocation resulting in MEF2C::SS18 gene fusion. Six primary cutaneous MSA cases have been recently described. We report three additional cases confirming the relevance of this recently identified entity of primary cutaneous adnexal tumor. Three patients aged 53-, 64- and 78-year-old were retrospectively diagnosed with MSA of the skin (MSAS) as consultation cases of the CARADERM (CAncers RAres DERMatologiques) national network. The clinical presentation was an indolent nodule on the upper extremities. There was no history of salivary gland tumor. Histopathologically, the tumors presented as dermal nodular proliferation with slightly infiltrative borders, composed of cribriform and microcystic structures with abundant myxoid intraluminal secretion embedded in a fibromyxoid stroma. They diffusely expressed cytokeratin 8 and SOX10, focally p63 and heterogeneously smooth muscle actin. All tumors harbored the MEF2C::SS18 gene fusion. A complete surgical excision was performed. No local recurrence or distant metastases were observed so far (follow-up: 17, 38, and 45 months). MSAS is the cutaneous homologue of MSA of the salivary gland, a low-grade adnexal neoplasm whose prognosis seems to be excellent once the complete removal of the tumor is assured.

Superficial (nodular) thrombophlebitis as a heterogeneous entity with distinctive clinico-pathological aspects: Correlation with the underlying conditions.

BACKGROUND: Superficial (nodular) thrombophlebitis, referring to a thrombo-inflammatory disorder of dermal-subcutaneous veins, encompass a spectrum of nodular lesions often associated with inflammatory, infectious, neoplastic or thrombophilic diseases. OBJECTIVE: We postulate that distinct clinico-pathological features may correlate with the underlying conditions. METHODS: We conducted a retrospective monocentric study of all patients seen in our dermatology department for a superficial thrombophlebitis, completed with a literature review. Clinical and pathological data were extracted from the patient files and articles. RESULTS: A total of 108 cases of superficial thrombophlebitis was analysed. Forty-five percent manifested as elongated nodules clearly evoking vascular involvement, while the other 55% were presenting as nodules or plaques. The elongated phenotype was strongly associated with malignancy or thrombophilia if a pure thrombosis was demonstrated histopathologically, while tuberculosis was the main underlying condition if a granulomatous vasculitis was present. Panniculitis-like lesions were mainly corresponding to erythema-nodosum-like lesions of Behçet's disease, characterized by the distinctive feature of thrombotic veins with an associated leukocytoclastic vasculitis. LIMITATIONS: Retrospective design and risk of publication bias. CONCLUSION: Superficial (nodular) thrombophlebitis is a heterogeneous entity with a distinct clinico-pathological presentation that strongly points to the nature of the underlying medical condition, thus guiding the medical workup.

Plasma cell-directed therapies in monoclonal gammopathy-associated scleromyxedema.

Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French multicenter retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and leonine facies (39%). MG involved an immunoglobulin G isotype in all patients, with a predominant λ light chain (73%). Associated hematologic malignancies were diagnosed in 4 of 33 patients (12%) (smoldering myeloma, n = 2; chronic lymphoid leukemia, n = 1; and refractory cytopenia with multilineage dysplasia, n = 1). Carpal tunnel syndrome (33%), arthralgia (25%), and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. High-dose IV immunoglobulin (HDIVig), alone or in combination with steroids, appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4 of 5 patients. Quantitative reverse-transcriptase polymerase chain reaction analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor ß and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.

Measurement of histological clearance margins in basal cell carcinoma.

AIMS: Basal cell carcinoma (BCC) is a common cancer, with a high risk of local recurrence. A quantifiable measurement of the histological margins of BCC in excisions is a recurrent demand of clinicians; however, there are currently no international guidelines indicating its value. METHODS AND RESULTS: A questionnaire validated by four experts in dermatopathology and formatted under a 'Google Forms'-type interface was sent by e-mail to physicians specializing in surgical pathology or dermatopathology and practising in France from 20 March 2018 to 20 May 2018. The results were compared between subgroups according to age and subspecialisation, especially dermatopathology. The questionnaire was completed by 225 practitioners. Microscopic margins were systematically measured in 77.3% of cases, sometimes in 19.6% and never in 3.1%. The main reason was to report factually insufficient margins (66.5%), followed by laboratory routine (45%) or clinician requests (43.1%). For 72% of respondents, the clinical or histopathological criteria did not influence their practice. The most used tool was a graduated ruler placed under a microscope (44.3% of cases). Compared to other groups, dermatopathologists measured BCC margins less systematically [only in certain situations (33.3 versus 14.9%) or never (10.5 versus 0.6%) (P < 0.001)] and used an eyepiece reticle more extensively (53.1 versus 29.8%; P = 0.0029). CONCLUSION: The measurement of histological margins in BCC is common practice in France, although there are no recommendations. Our survey suggests that it represents a way for pathologists to specify an insufficient margin and therefore the need for scar revision.

Epidemiology of Merkel cell carcinoma. A population-based study from 1985 to 2013, in northeastern of France.

Merkel Cell Carcinoma (MCC) is an aggressive skin cancer with an increasing incidence. Population-based epidemiologic data about MCC in France are rare. Our study aims to describe the epidemiology of MCC in Bas-Rhin, Northeastern of France, between 1985 and 2013. Data were collected from the Bas-Rhin Cancer Registry. We measured age-adjusted incidence rates (per 100,000 person-years) and effect of age, sex and period of diagnosis on survival. The world age-standardized incidence rate was 0.17 and it quadrupled between 1985 and 2013. Cases (n = 111) occurred mostly in women (60%) and in persons ≥70 years of age (74%). Incidence rates was close for men (0.18) and women (0.16) and was 25-time higher in people ≥70 years of age but incidence rate similarly increased between 1985 and 2013 in persons older and younger than 70 years. Net 5-year survival was 48.5%; female sex and younger age were positive predictors of survival. Given the low number of cases, incidence and survival data should be interpreted with caution. Incidence of MCC in Bas-Rhin quadrupled between 1985 and 2013. The highest incidence rate was observed in people ≥70 years. Better survival was associated with female sex and younger age. We hypothesize that MCC will still increase and be diagnosed in increasingly younger patients in next generations.

Heterogeneity of PD-L1 expression and CD8 tumor-infiltrating lymphocytes among subtypes of cutaneous adnexal carcinomas.

BACKGROUND: Adnexal carcinomas are rare and heterogeneous skin tumors, for which no standard treatments exist for locally advanced or metastatic tumors. AIM OF THE STUDY: To evaluate the expression of PD-L1 and CD8 in adnexal carcinomas, and to study the association between PD-L1 expression, intra-tumoral T cell CD8+ infiltrate, and metastatic evolution. MATERIALS AND METHODS: Eighty-three adnexal carcinomas were included. Immunohistochemistry using anti-PD-L1 monoclonal antibodies (E1L3N and 22C3) and CD8 was performed. PD-L1 expression in tumor and immune cells, and CD8+ tumor-infiltrating lymphocyte (TIL) density were analyzed semi-quantitatively. RESULTS: Among the 60 sweat gland, 18 sebaceous and 5 trichoblastic carcinomas, 11% expressed PD-L1 in ≥ 1% tumor cells, more frequently sweat gland carcinomas (13%, 8/60) including apocrine carcinoma (40%, 2/5) and invasive extramammary Paget disease (57%, 4/7). Immune cells expressed significantly more PD-L1 than tumor cells (p < 0.01). Dense CD8+ TILs were present in 60% trichoblastic, 43% sweat gland, and 39% sebaceous carcinomas. CD8+ TILs were associated with PD-L1 expression by tumor cells (p < 0.01). Thirteen patients out of 47 developed metastases (27%) with a median follow-up of 30.5 months (range 7-36). Expression of PD-L1 by tumor cells was associated with the development of metastasis in univariate analysis (HR 4.0, 95% CI 1.1-15, p = 0.0377) but not in multivariate analysis (HR 4.1, 95% CI 0.6-29, p = 0.15). CONCLUSION: PD-L1 expression is highly heterogeneous among adnexal carcinoma subtypes, higher in apocrine carcinoma and invasive extramammary Paget disease, and associated with CD8+ TILs. Our data suggest the interest of evaluating anti-PD1 immunotherapy in advanced or metastatic cutaneous adnexal carcinoma.

Are there distinct clinical and pathological features distinguishing idiopathic from drug-induced subacute cutaneous lupus erythematosus? A European retrospective multicenter study.

BACKGROUND: Clinical and pathologic criteria to distinguish drug-induced subacute lupus erythematosus (DI-SCLE) from idiopathic (I-SCLE) are controversial. OBJECTIVE: The aim of the survey was a retrospective analysis of a consistent number of iatrogenous and idiopathic SCLE cases, by means of clinical and histopathologic investigation. METHODS: Eleven European university dermatology units collected all diagnosed cases from January 2000 to December 2016. Board-certified dermatopathologists reviewed the histopathologic specimens. Statistical analysis included Student t test, exact test of goodness-of-fit, Fisher's exact test, and the Cochran-Mantel-Haenszel test for repeated measures. RESULTS: Out of 232 patients, 67 (29%) belonged to the DI-SCLE group. Patients with DI-SCLE were significantly older and reported more systemic symptoms than those with I-SCLE. No statistical differences were found for presentation pattern or serology, while histopathology showed a significant association of mucin deposition (P = .000083), direct immunofluorescence positivity for granular immunoglobulin M, and C3 deposits on the basement membrane zone (P = .0041) for I-SCLE and of leukocytoclastic vasculitis (P = .0018) for DI-SCLE. LIMITATIONS: This is a retrospective study. CONCLUSION: An integrated clinical and immunopathologic evaluation is useful to differentiate I-SCLE from DI-SCLE. Older age at onset and more frequent systemic symptoms characterize DI-SCLE. Mucin deposition and immunofluorescence findings are found in I-SCLE, and leukocytoclastic vasculitis is found in DI-SCLE.

Primary cutaneous ganglioneuroma: anatomico-clinical study of 4 cases with focus on Merkel cells.

Cutaneous ganglioneuromas (CGNs) are exceptional. We aim to describe the anatomico-clinical profile of primary CGN and report 4 cases. Patients were 2 men and 2 women aged 53 to 76 years, who had flesh-colored nodules on the back, associated with adjacent keratotic changes, that is, epidermal nevus (1 case) or seborrheic keratosis (3 cases). Histopathology showed ganglion cells within a proliferation of Schwann cells. The epidermis was acanthotic, associated with sebaceous induction in 2 cases, with follicular hyperplasia as in fibroepithelial tumors (1 case) or with tricholemmoma (2 cases). Cytokeratin-20 immunostaining showed Merkel cells in the epidermis. A higher density of Merkel cells was observed in BerEP4+ follicular structures. Along with 16 published cases, our study indicates that a nodule associated with seborrheic keratosis on the back may represent a CGN, a complex mesenchymal and epidermal/follicular lesion of neuroectodermal lineage, associating neuronal proliferation and Merkel cell hyperplasia with follicular induction.

Aggressive digital papillary adenocarcinoma: A clinicopathological study of 19 cases.

BACKGROUND: Aggressive digital papillary adenocarcinomas (ADPA) are malignant tumors of sweat glands having recurrence/metastatic potential. OBJECTIVE: We sought to describe the clinical/histopathological characteristics of a series of ADPA. METHODS: This is a retrospective case series of 19 ADPA. RESULTS: The tumors occurred in 17 men and 2 women (mean age: 47 years). They involved digits (15), big toe (3), and palm (1), and measured from 3 to 30 mm. They were mostly solid and cystic, with papillary projections and tubular structures. Atypia was mostly mild to moderate. Tumors tested positive for p63, keratin 7, keratin 77 (eccrine duct-specific), PHLDA1, and epithelial membrane antigen in most cases, and for carcinoembryonic antigen, smooth muscle actin, S100 protein, estrogen, progesterone, and androgen receptors in 50%. Mean Ki67 proliferation index was 15%. Local recurrence was observed in 4 cases. One patient had axillary lymph node metastasis. Histopathologic parameters were not predictive of evolution. Conservative surgical treatment, performed in 7 of 19 cases, did not result in more recurrences than amputation. LIMITATIONS: The study was retrospective and the number of cases is small. CONCLUSION: ADPA are histologically variable, but papillary projections are always present. Keratin 77 expression suggests an eccrine origin. P63 is helpful to exclude metastasis. Conservative surgery may be sufficient in some cases.