A novel method to assess copy number variations in melanocytic neoplasms: Droplet digital PCR for precise quantitation of MYC and MYB genes.

INTRODUCTION: While most melanocytic neoplasms can be classified as either benign or malignant by histopathology alone, ancillary molecular diagnostic tests can be necessary to establish the correct diagnosis in challenging cases. Currently, the detection of copy number variations (CNVs) by fluorescence in situ hybridization and chromosomal microarray (CMA) are the most popular methods, but remain expensive and inaccessible. We aim to develop a relatively inexpensive, fast, and accessible molecular assay to detect CNVs relevant to melanoma using droplet digital polymerase chain reaction (ddPCR) technology. METHODS: In this proof-of-concept study, we evaluated CNVs in MYC and MYB genes from 73 cases of benign nevi, borderline melanocytic lesions, and primary and metastatic melanoma at our institution from 2015 to 2022. A multiplexed ddPCR assay and CMA were performed on each sample, and the results were compared. RESULTS: Concordance analysis of ddPCR with CMA for quantification of MYC and MYB CNVs revealed a sensitivity and specificity of 89% and 86% for MYC and 83% and 74% for MYB, respectively. CONCLUSION: We demonstrate the first use of a multiplexed ddPCR assay to identify CNVs in melanocytic neoplasms. With further improvement and validation, ddPCR may represent a low-cost and rapid tool to aid in the diagnosis of histopathologically ambiguous melanocytic tumors.

Anti-PL-7, anti-Ro/SSA, anti-Mi-2, and anti-TIF1-γ correlate with specific patterns of histopathologic features in dermatomyositis: An analysis of 39 skin biopsy specimens from 25 patients.

BACKGROUND: In dermatomyositis (DM), myositis-specific and myositis-associated antibodies have been correlated with clinical features. It is unknown if histopathologic findings in lesional skin biopsies correlate with serologic subtypes of DM. METHODS: A retrospective chart review of patients with DM was performed. Patients with myositis antibodies and DM lesional skin biopsies were included in the study. Skin biopsies were reviewed by blinded dermatopathologists for 20 histopathologic features. RESULTS: There was a statistically significant (p < 0.05) association between anti-PL-7 serology and decreased degree of vacuolar degeneration, necrotic keratinocytes, and thickening of the epidermal basement membrane. Anti-aminoacyl tRNA synthetase (anti-ARS) antibodies had the same significant negative association with degree of vacuolar degeneration, necrotic keratinocytes, and thickening of the epidermal basement membrane. A similar pattern was seen with an anti-cytoplasmic serology; where there was a significant association with an increased degree of vacuolar degeneration and necrotic keratinocytes, and a nonsignificant trend of minimally thickened epidermal basement membrane. There was a statistically significant association between anti-Ro/SSA serology and increased degree of vacuolar degeneration. Anti-TIF1-γ serology was significantly associated with the increased presence of necrotic keratinocytes and pigment incontinence, and displayed a pattern of increased neutrophils. There was a significant association between anti-Mi-2 antibodies and pigment incontinence, as well as between myositis-specific antibodies and pigment incontinence. A statistically significant positive association was found between nuclear antibodies and degree of vacuolar degeneration, thickened epidermal basement membrane, pigment incontinence, and epidermal atrophy. CONCLUSION: In patients with DM, some specific serotypes, including anti-PL-7, anti-Ro/SSA, anti-Mi-2, and anti-TIF1-γ, may have characteristic histopathologic features.

Squamoid eccrine ductal carcinoma: clinical, histological and immunohistochemical features.

Squamoid eccrine ductal carcinoma (SEDC) is a cutaneous adnexal malignancy that is histologically challenging to distinguish from squamous cell carcinoma. We report three cases of this rare entity and review the present literature regarding clinical, histological, and immunohistochemical features. Patients presented with a single nodule or plaque lesion on their back and temple. The shave biopsies for Patient A and C were interpreted as SEDC. Patient B's initial shave biopsy was interpreted as probable surface of squamous cell carcinoma, and subsequent excision revealed SEDC. Ductal differentiation was confirmed by positive expression of epithelial membrane antigen and carcinoembryonic antigen immunostains in all three patients. Review of the 67 previously reported cases emphasizes the importance of diagnosing SEDC accurately and promptly given its potential for distant metastasis and mortality. Perineural or lymphatic invasion is associated with higher rate of recurrence or metastasis. There should be high pathologic suspicion for SEDC in an elderly patient presenting with a palpable lesion, even if located outside of the head and neck area, particularly when there is suggestion of ductal differentiation in a sample of a squamous neoplasm.

Histiocytoid melanoma: Diagnostic pitfall and mimicker of non-Langerhans cell histiocytoses including reticulohistiocytoma.

Melanoma and benign histiocytic proliferations can sometimes show considerable clinical and histopathologic overlap. Recently, cases of melanomas resembling xanthogranuloma and Rosai-Dorfman disease have been reported, and herein we report a case of melanoma closely mimicking reticulohistiocytoma. An 84-year-old man presented with a 1 cm purple-red nodule on his arm concerning for squamous cell carcinoma. While the biopsy findings resembled reticulohistiocytoma, the clinical context and regression changes at the lesion perimeter raised stronger concern for melanoma, which was confirmed with immunohistochemistry. We review prior rare reports of melanomas resembling non-Langerhans cell histiocytic proliferations and summarize helpful clinical and histopathologic clues to avoid a diagnostic pitfall when confronted with this unusual quandary.

PRAME expression in cutaneous melanoma does not correlate with disease-specific survival.

BACKGROUND: Immunohistochemistry-based protein biomarkers can provide useful prognostic information in cutaneous melanoma. The independent prognostic value of Ki-67 has been studied with variable results. PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemistry is a useful new ancillary tool for distinguishing cutaneous nevi from melanoma; however, its prognostic value has not been well studied. We evaluated PRAME as a prognostic marker in cutaneous melanoma, compared to Ki-67. METHODS: We analyzed the immunohistochemical expression of PRAME and Ki-67 in 165 melanocytic lesions, including 92 primary melanomas, 19 metastatic melanomas, and 54 melanocytic nevi using tissue microarrays. PRAME immunostaining was scored based on the percentage of positive nuclei: 0 <1%, 1+ 1%-25%, 2+ 26%-50%, 3+ 51%-75%, and 4+ >75%. The percentage of Ki-67-positive tumor nuclei was used to calculate the proliferation index. RESULTS: PRAME and Ki-67 both showed significantly increased expression in melanomas compared to nevi (p < 0.0001 and p < 0.001, respectively). There was no significant difference in PRAME expression in primary versus metastatic melanomas. By contrast, the Ki-67 proliferation index was higher in metastatic melanoma than in primary melanoma (p = 0.013). Increased Ki-67 index correlated with ulceration (p < 0.001), increased Breslow depth (p = 0.001), and higher mitotic rate (p < 0.0001), whereas increased PRAME expression correlated with higher mitotic rate (p = 0.047) and Ki-67 index (p = 0.007). Increased Ki-67 index correlated with worse disease-specific survival in patients with primary melanoma (p < 0.001), but PRAME expression did not show prognostic significance in disease-specific survival (p = 0.63). In a multivariable analysis of patients with primary melanoma, tumor Breslow depth, ulceration, mitotic rate, and Ki-67 index were each independent predictors of disease-specific survival (p = 0.006, 0.02, 0.001, and 0.04, respectively); however, PRAME expression was not predictive of disease-specific survival (p = 0.64). CONCLUSION: Ki-67 is an independent prognostic marker; although increased PRAME expression correlates with the Ki-67 proliferation index and mitotic rate, PRAME is not an independent prognostic marker for cutaneous melanoma. PRAME and Ki-67 are useful ancillary tools for distinguishing benign from malignant melanocytic lesions.

A Novel Method to Detect Copy Number Variation in Melanoma: Droplet Digital PCR for Quantitation of the CDKN2A Gene, a Proof-of-Concept Study.

ABSTRACT: A definitive diagnosis of nevus or melanoma is not always possible for histologically ambiguous melanocytic neoplasms. In such cases, ancillary molecular testing can support a diagnosis of melanoma if certain chromosomal aberrations are detected. Current technologies for copy number variation (CNV) detection include chromosomal microarray analysis (CMA) and fluorescence in situ hybridization. Although CMA and fluorescence in situ hybridization are effective, their utilization can be limited by cost, turnaround time, and inaccessibility outside of large reference laboratories. Droplet digital polymerase chain reaction (ddPCR) is a rapid, automated, and relatively inexpensive technology for CNV detection. We investigated the ability of ddPCR to quantify CNV in cyclin-dependent kinase inhibitor 2A ( CDKN2A ), the most commonly deleted tumor suppressor gene in melanoma. CMA data were used as the gold standard. We analyzed 57 skin samples from 52 patients diagnosed with benign nevi, borderline lesions, primary melanomas, and metastatic melanomas. In a training cohort comprising 29 randomly selected samples, receiver operator characteristic curve analysis revealed an optimal ddPCR cutoff value of 1.73 for calling CDKN2A loss. In a validation cohort comprising the remaining 28 samples, ddPCR detected CDKN2A loss with a sensitivity and specificity of 94% and 90%, respectively. Significantly, ddPCR could also identify whether CDKN2A losses were monoallelic or biallelic. These pilot data suggest that ddPCR can detect CDKN2A deletions in melanocytic tumors with accuracy comparable with CMA. With further validation, ddPCR could provide an additional CNV assay to aid in the diagnosis of challenging melanocytic neoplasms.

Primary cutaneous gamma-delta T-cell lymphoma masquerading as leukemia cutis in a patient recently diagnosed with small lymphocytic lymphoma: Clues to the diagnosis.

A 54-year-old man recently diagnosed with small lymphocytic lymphoma (SLL) had waxing and waning, indurated, erythematous plaques on his legs, with leukopenia and anemia disproportionate to the SLL burden in his marrow and pelvic lymph nodes. Punch biopsy of a plaque performed to evaluate for leukemia cutis revealed a lymphocytic lobular-panniculitis-like infiltrate resembling lupus panniculitis, but a preponderance of CD8+/Ki-67+ T-cells surrounding adipocytes raised concern for subcutaneous panniculitis-like T-cell lymphoma (SPTCL). Additional immunohistochemistry (IHC) studies showed that the adipotropic T-cells expressed TCR-gamma, supporting the rare, unexpected diagnosis of Primary cutaneous gamma-delta T-cell lymphoma (PCGDTCL). The patient subsequently met diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH). PCGDTCL is an aggressive, HLH-associated lymphoma requiring different management than SPTCL and SLL. This case illustrates how PCGDTCL can co-exist with B-cell lymphoma and resemble panniculitis on biopsies. PCGDTCL and SPTCL should enter the differential diagnosis whenever patients present with the constellation of lobular panniculitis and unexplained cytopenias. In the present case, close clinicopathologic correlation and judicious use of IHC on a small sample allowed for a prompt diagnosis.

Molecular analysis of NUT-positive poromas and porocarcinomas identifies novel break points of YAP1::NUTM1 fusions.

BACKGROUND: Poromas, and their malignant counterparts, porocarcinomas, harbor recurrent translocations involving YAP1-MAML2, YAP1-NUTM1, and infrequently WWTR1-NUTM1; YAP1-NUTM1 being the most common in porocarcinomas. NUT immunohistochemistry (IHC) can be used to identify NUTM1-translocated tumors. This study sought to investigate potential novel NUTM1-fusion partners among NUT IHC-positive poromas and porocarcinomas. METHODS: Thirteen NUT IHC-positive poroid tumors (four poromas and nine porocarcinomas) were identified within a multi-institutional international cohort. Next-generation sequencing (NGS) assessed for NUTM1 fusion partners. RESULTS: NGS detected a NUTM1 fusion in 12 of 13 cases: YAP1-NUTM1 (11/12 cases) and WWTR1-NUTM1 (1/12 cases). Two of the cases (2/12) with NUTM1 fusion were not called by the NGS algorithm but had at least one read-spanning YAP1-NUTM1 break point upon manual review. A NUTM1 fusion was not identified in one case; however, the sample had low RNA quality. The following fusion events were identified: YAP1 exon 4::NUTM1 exon 3 in six cases, YAP1 exon 6::NUTM1 exon 2 in one case, YAP1 exon 3::NUTM1 exon 3 in three cases, WWTR1 exon 3::NUTM1 exon 3 in one case, and YAP1 exon 8::NUTM1 exon 3 fusion in one case. CONCLUSION: While no novel NUTM1 fusion partners were identified within our cohort, 12 of 13 cases had discoverable NUTM1 fusions; YAP1-NUTM1 fusion was detected in 11 cases (92%) and WWTR1-NUTM1 in 1 case (8%). These data corroborate findings from other recent investigations and further substantiate the utility of NUT IHC in diagnosing a subset of poroid neoplasms. In addition, two of our cases harbored fusions of YAP1 exon 6 to NUTM1 exon 3 and YAP1 exon 8 to NUTM1 exon 2, which have not been reported before in poroid neoplasms and indicate novel break points of YAP1.

Unraveling subcutaneous panniculitis-like T-cell lymphoma: An association between subcutaneous panniculitis-like T-cell lymphoma, autoimmune lymphoproliferative syndrome, and familial hemophagocytic lymphohistiocytosis.

Germline HAVCR2 mutations, recently identified in a large subset of patients with subcutaneous panniculitis-like T-cell lymphoma (SPTCL), are associated with an increased risk of hemophagocytic lymphohistiocytosis (HLH). Discovery of this heritable HLH/SPTCL diathesis has expanded our understanding of a rare and molecularly heterogeneous lymphoma. Furthermore, patients with SPTCL have excellent survival unless they develop HLH. Therefore, through compiling data on SPTCL-related conditions that predispose patients to HLH, we are better able to predict which patients with SPTCL have the greatest risk of mortality. We present the first case of SPTCL with concomitant HLH and autoimmune lymphoproliferative syndrome (ALPS) in a patient who was subsequently diagnosed with familial HLH (F-HLH) attributable to a germline STXBP2 splice-site mutation. She had wild-type HAVCR2. Reports including ours show how SPTCL can evolve in the setting of an exaggerated host inflammatory response attributable to a variety of unusual underlying etiologies.

Small lymphocytic lymphoma mimicking primary cutaneous marginal zone lymphoma with colonization of germinal center follicles.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is primarily a disease of older adults and is occasionally an incidental finding on skin biopsies accompanying epithelial neoplasms and insect bite reactions. In rare instances, however, it produces leukemic infiltrates showing clinical and histopathologic overlap with primary cutaneous B-cell lymphomas including primary cutaneous marginal zone lymphoma (PCMZL). Even less frequently, such findings serve as the initial disease manifestation. We present an exceptional case of a 61-year-old man with no past medical history whose clinical and histopathologic findings raised consideration for PCMZL with abnormal B-cells colonizing germinal center follicles; however, faint CD5 and CD23 co-expression raised the differential diagnosis of CLL/SLL. In light of an ambiguous clinical presentation with widely distributed papules and plaques, peripheral blood flow cytometry was also performed, revealing high count of CLL-type monoclonal B lymphocytosis. Subsequent workup revealed bone marrow involvement and mesenteric lymphadenopathy, supporting the diagnosis of SLL. Follicular colonization by SLL has not been previously reported. Our case underscores the importance of subtle immunophenotypic clues and correlations with clinical and radiologic findings in the workup of B-cell lymphomas presenting in the skin.

PRAME immunohistochemistry is useful in the evaluation of conjunctival melanomas, nevi, and primary acquired melanosis.

BACKGROUND: Many dermatopathologists find conjunctival melanocytic proliferations challenging because they are rare relative to their cutaneous counterparts and have nuanced morphology and nomenclature. PRAME immunohistochemistry has been widely adopted for distinguishing cutaneous nevi from melanoma, but limited data exist assessing its utility in evaluating conjunctival specimens. In particular, it is uncertain whether it can predict the risk of melanoma progression in primary acquired melanosis (PAM). METHODS: Thirty clinically annotated cases (two melanomas, three PAM with atypia, seven PAM without atypia, 15 nevi, two combined nevi, and a diagnostically challenging nevus with atypical features) were retrospectively evaluated with PRAME. RESULTS: Strong, diffuse PRAME expression was present in melanomas and PAM with high-grade atypia, but not in PAM with low-grade atypia, PAM without atypia, or nevi. Scattered, faintly PRAME-positive intraepithelial melanocyte nuclei were identified in six nevi. A clonal nevus and nests of heavily pigmented type-A melanocytes in two additional nevi had cytoplasmic staining. CONCLUSIONS: PRAME was useful for distinguishing melanoma and its probable precursors from benign conjunctival melanocytic proliferations in our cohort. The data alert us to two diagnostic pitfalls in nevi: scattered, PRAME-positive intraepithelial melanocytes and cytoplasmic PRAME staining in type-A melanocytes and melanophages. Larger scale investigations are warranted to further substantiate these promising findings.

Comparative performance of insulinoma-associated protein 1 (INSM1) and routine immunohistochemical markers of neuroendocrine differentiation in the diagnosis of endocrine mucin-producing sweat gland carcinoma.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare cutaneous adnexal malignancy with predilection for the eyelids of older adults. It must be distinguished from metastatic adenocarcinomas of extracutaneous origin and from benign adnexal proliferations on partial samples when a solid growth component and mucin production are not evident. Thus, demonstration of neuroendocrine differentiation can help to ensure a correct diagnosis. Insulinoma-associated protein 1 (INSM1) is a novel neuroendocrine marker that has recently shown greater sensitivity than synaptophysin (SYN) and chromogranin (CHR) in the diagnosis of various neuroendocrine neoplasms. We compared the performance of these three markers across 10 examples of EMPSGC. All EMPSGCs expressed INSM1. Eight of ten were also immunoreactive for SYN; however, INSM1 staining was generally more intense and stained a greater proportion of the tumor cells. CHR staining was weak and focal in most cases. INSM1 staining was present in hidrocystoma-like components of cystic EMPSGC. These findings suggest that INSM1 may be more sensitive than SYN and CHR and thus valuable for establishing a diagnosis of EMPSGC.

Comparison of adipophilin and recently introduced PReferentially expressed Antigen in MElanoma immunohistochemistry in the assessment of sebaceous neoplasms: A pilot study.

BACKGROUND: We and others have noticed consistent staining of sebaceous glands with PReferentially expressed Antigen in MElanoma (PRAME). We aimed to determine whether PRAME was as sensitive, specific, and interpretable as adipophilin for distinguishing sebaceous neoplasms (SNs) from other neoplasms. METHODS: Twenty SNs and 32 control cases were stained for PRAME and adipophilin. Extent of staining was scored as follows: 0, no staining; 1, <5% positivity; 2, 5% to 50% positivity; and 3, >50% positivity. Intensity was scored as negative, weak, moderate, or strong. A composite score was determined by adding the scores for extent and intensity. RESULTS: PRAME had positive composite scores in all 20 SNs in the more differentiated areas, whereas adipophilin had positive composite scores in 19/20 cases. PRAME showed positivity in the basaloid cells in 15/16 cases, whereas adipophilin was positive in 14. Among controls, PRAME and adipophilin had positive composite scores in 3/32 cases and 6/32 cases, respectively. CONCLUSIONS: PRAME and adipophilin are comparable in terms of distribution and intensity for staining sebocytes. In the basaloid cells, PRAME expression is often more diffuse and easier to detect than adipophilin. In comparing the SNs to the controls, PRAME was more sensitive and more specific than adipophilin. PRAME could be used as an additional marker of sebaceous differentiation in everyday practice.

Ethical and professionalism issues in dermatopathology: A cross-sectional survey of American Society of Dermatopathology Members.

BACKGROUND: Data regarding ethical/professional issues affecting dermatopathologists are lacking despite their importance in establishing policy priorities and educational content for dermatopathology. METHODS: A 14-item cross-sectional survey about ethical/professional issues in dermatopathology was distributed over e-mail to members of the American Society of Dermatopathology from June to September 2019. RESULTS: Two hundred sixteen surveys were completed, with a response rate of 15.3%. Respondents ranked appropriate and fair utilization of healthcare resources (n = 83 or 38.6%) as the most often encountered ethical/professional issue. Conflict of interest was ranked as the most urgent or important ethical/professional issue (n = 83 or 39.3%). One hundred thirty-three (61.6%) respondents felt "somewhat" or "not at all" well equipped to handle ethical dilemmas in practice and 47 (22.8%) respondents identified a major or extreme burden (eg, have considered resigning/retiring) due to ethical challenges. CONCLUSIONS: Areas of priority in ethics and professionalism issues can guide future policy and educational content in dermatopathology.

Novel LRRFIP2-RAF1 fusion identified in an acral melanoma: A review of the literature on melanocytic proliferations with RAF1 fusions and the potential therapeutic implications.

A small subset of cutaneous melanomas harbor oncogenic gene fusions, which could potentially serve as therapeutic targets for patients with advanced disease as novel therapies are developed. Fusions involving RAF1 are exceedingly rare in melanocytic neoplasms, occurring in less than 1% of melanomas, and usually arise in tumors that are wild type for BRAF, NRAS, and NF1. We describe herein a case of acral melanoma with two satellite metastases and sentinel lymph node involvement. The melanoma had a concomitant KIT variant and LRRFIP2-RAF1 fusion. This constellation of molecular findings has not been reported previously in melanoma. We review the existing literature on melanocytic neoplasms with RAF1 fusions and discuss the potential clinical implications of this genetic event.

Sarcoidosis with small syringotropic granulomas presenting clinically as a pigmented purpuric dermatosis: Inconspicuous clinical and histopathological clues to systemic illness.

Sarcoidosis is a multisystem granulomatous disease with a myriad of clinical manifestations and a predilection to involve the lungs, eyes, lymph nodes, and skin. A 38-year-old man presented to dermatology with a history of progressive dyspnea, pulmonary consolidations on chest X-ray, and hilar adenopathy on computed tomography scan. Skin exam revealed asymptomatic, yellow to brown macules on the right lower extremity. Biopsy of a lesion showed diminutive syringotropic granulomas and perivascular hemosiderin; stains for bacteria, mycobacteria, and fungi were negative. Subsequent fine needle aspiration of a hilar mass revealed non-necrotizing epithelioid granulomas further supporting a diagnosis of sarcoidosis. The patient was placed on systemic steroids and had improvement of his pulmonary symptoms and stabilization of his hilar lymphadenopathy without resolution of his pigmented purpuric dermatosis (PPD) like lesions. Only three prior cases of syringotropic sarcoidosis have been reported; however, the biopsies had revealed conspicuously large granulomas in contrast with the small granulomas in our case, and none of the prior patients had clinical examination findings that mimicked PPD. Recognition of rare dermatologic and histopathological appearances of sarcoidosis is paramount as cutaneous sarcoidosis may be the harbinger of a systemic illness, which requires a timely diagnosis.

Post-scabietic nodules: Mimicker of infantile indeterminate cell histiocytosis and potential diagnostic pitfall.

Indeterminate cell histiocytosis (ICH) is an extremely rare disease and little is known about its etiology. Patients usually present with nodular, dermal proliferations of indeterminate cells, which characteristically resemble Langerhans cells but lack Birbeck granules. The clinical course is highly variable, ranging from spontaneous regression to rapid progression with reports of extracutaneous involvement, subsequent acute myeloid leukemias, and associated B-cell lymphomas. Rare cases of ICH-like reactions have been reported in the setting of scabies infestations as well as in patients who had been bitten by ticks and mosquitos. We present a successfully treated case of indeterminate cell-rich post scabietic nodules in an otherwise healthy 8-month-old boy and review the literature on similar cases. Clinical context is essential for correct interpretation of these indolent ICH-mimicking lesions, and to avert unnecessary patient anxiety and aggressive management.

CD10 and p63 expression in a sarcomatoid undifferentiated melanoma: A cautionary (and molecularly annotated) tale.

Undifferentiated melanoma should be considered in the differential diagnosis of sarcomatoid cutaneous malignancies to ensure that patients receive the correct treatment. Dermatopathologists should recognize the pitfalls of relying too heavily on immunohistochemistry to establish this diagnosis and consider ancillary tests, including single-nucleotide polymorphism (SNP) copy number arrays and targeted next-generation sequencing (NGS), when a definitive diagnosis cannot be rendered on a primary or metastatic tumor. This technology can also help to exclude a collision of melanoma and sarcoma when both differentiated and undifferentiated components are juxtaposed. We describe an exceedingly rare, illustrative example of undifferentiated sarcomatoid melanoma presenting as a pedunculated nodule. The clinical context and presence of a small differentiated component helped to establish the diagnosis; however, the transition from differentiated to undifferentiated melanoma was accompanied by an abrupt loss of S100, Sox10, MITF, MelanA, and HMB45 with gain of CD10 and p63 staining. SNP copy number array and NGS revealed shared chromosomal copy number changes and overlapping mutations with additional aberrances detected exclusively in the sarcomatoid component, thereby excluding a collision tumor and confirming our putative impression of melanoma with progression to an undifferentiated sarcomatoid phenotype.

Metastatic Mimics of Primary Cutaneous Lesions: Averting Diagnostic Pitfalls With Significant Repercussions.

Cutaneous metastases by solid malignancies often signify advanced disease and portend severely limited survival. Appropriate diagnosis of these lesions is particularly hampered when they closely resemble primary cutaneous tumors. In this article, we present two diagnostically challenging cases of metastatic lesions to the scalp bearing striking histologic resemblance to primary cutaneous neoplasms. One case of a metastatic urothelial carcinoma showed epidermotropism as well as histologic and immunohistochemical features virtually indistinguishable from those of a poorly differentiated squamous cell carcinoma. Next generation sequencing was performed on both the primary urothelial carcinoma and scalp malignancy revealing an identical BRAF p. S467L somatic mutation, confirming the diagnosis. Another case of metastatic renal cell carcinoma showed clinical and histomorphologic features highly reminiscent of a pyogenic granuloma. These cases demonstrate the potential of metastatic lesions to assume a myriad array of innocuous disguises and underscore the vigilance required to avoid misdiagnosis. In addition, we highlight the emerging role of molecular strategies in resolving these problematic cases.

Kikuchi-Fujimoto disease preceded by lupus erythematosus panniculitis: do these findings together herald the onset of systemic lupus erythematosus?

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare disorder that must be distinguished from systemic lupus erythematosus (SLE). Although a minority of patients with KFD develop SLE, most patients have a self-limited disease. Importantly, KFD can have skin manifestations resembling cutaneous lupus. Therefore, the diagnosis of SLE should be predicated on a complete rheumatologic workup and not on the constellation of skin disease and lymphadenitis. Nonetheless, as our exceedingly rare case illustrates, patients who do not initially meet diagnostic criteria for SLE require dermatologic follow-up. We present a young adult woman who had a remote history of KFD and later presented with combined features of discoid lupus and lupus erythematosus panniculitis (LEP). On subsequent rheumatologic workup, she fulfilled criteria for SLE. We discuss the differential diagnosis of both KFD and LEP and emphasize how strong communication among dermatologists and other healthcare providers is essential in the management of patients with KFD.