Low-grade fibromyxoid sarcoma (LGFMS) arising at acral sites is exceedingly rare, and its clinicopathologic features and clinical outcomes remain poorly characterized. Herein, we report a cohort of ten cases of acral LGFMS. The cohort included six males and four females, with a mean age at diagnosis of 23 years (median, 14 years; range, 2–67 years). Tumors arose in the foot (n = 7) or hand (n = 3). All cases were superficially located and exhibited classic morphologic features of LGFMS. Diffuse MUC4 expression was observed in all nine cases tested. Fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) demonstrated FUS gene rearrangements in all five cases analyzed. Clinical follow-up was available for six patients, with a mean duration of 37 months (range, 6–91 months). One patient developed a local recurrence and subsequently underwent digital amputation. No patients have developed metastases to date. Recognition of this rare, deceptively bland neoplasm in acral locations is critical, given its potential for local recurrence and metastatic spread.

CIC-rearranged sarcoma is a rare and aggressive undifferentiated round cell sarcoma that presents significant diagnostic challenges due to its histologic overlap with other round cell sarcomas. This review, conducted on behalf of the American Society of Dermatopathology Appropriate Use Criteria Committee (soft tissue subgroup), provides an overview of current immunohistochemical, cytogenetic, and molecular tests used to support the diagnosis of CIC-rearranged sarcoma. This comprehensive analysis included 36 studies, encompassing 436 CIC-rearranged sarcomas. The immunohistochemical markers, CD99 (typically non-diffuse), nuclear WT1, ETV4, and DUX4, were found to be relatively highly sensitive for CIC-rearranged sarcoma (CD99: 87%, WT1: 83%, ETV4: 85%, DUX4: 97%). However, the specificity of these markers is variable, with CD99 being highly non-specific, while WT1 (81%-90%), ETV4 (95%), and DUX4 (100%) offering greater specificity. CIC break-apart FISH can be a helpful and cost-effective assay for detection of CIC-rearrangements, but has a false-negative rate that ranges from 26% to 43%. Next-generation sequence RNA fusion analysis also carries a risk of false negatives, which may be partly mitigated through manual data review. Ultimately, an accurate diagnosis of CIC-rearranged sarcoma requires careful morphologic assessment in combination with immunohistochemical studies and cytogenetics/molecular assays.

The vulva and perineum are rarely involved by acantholytic dyskeratoses, including Hailey-Hailey disease, Darier disease, papular acantholytic dyskeratosis of the genitocrural area, acantholytic dyskeratotic acanthoma, and warty dyskeratoma. These entities show broad histomorphologic overlap, generally requiring clinical correlation for definitive classification. This institutional series aims to better characterize vulvar acantholytic dyskeratoses and provide a practical literature review and diagnostic aid for gynecologic pathologists. Our institutional archives contained 16 vulvar acantholytic dyskeratoses diagnosed between 1990 and 2023. Affected patients were 36 to 79 (mean, 58) years old and presented with one or more asymptomatic (n = 9) or pruritic (n = 6) lesions involving the vulva (predominantly the labia majora), with additional perineal involvement in 2. Four patients have known Hailey-Hailey disease. Eleven cases comprised singular, raised, erythematous, or skin-colored papules, measuring 0.2 to 0.6 (mean, 0.3) cm. Two patients had oligofocal (both with known Hailey-Hailey disease) vulvar lesions, and 2 had multifocal vulvar lesions (one with known Hailey-Hailey disease). Histologically, all showed acantholysis and dyskeratoses (abundant in 8, focal in 8, with corps ronds generally more conspicuous than corps grains). Additional features included suprabasal clefting (n = 14), dermal papillomatosis (n = 12), and acanthosis (n = 8). Adnexal involvement was rare (n = 1). No histologic features reliably distinguished sporadic versus syndromic acantholytic dyskeratoses. Sporadic lesions were cured by local excision. Patients with Hailey-Hailey disease were variably responsive to corticosteroids. Neither our series nor the literature indicate a significant correlation between sporadic or syndromic acantholytic dyskeratosis and squamous cell carcinoma. Important differential diagnoses include pemphigus vulgaris and pemphigus vegetans, for which direct immunofluorescence may be performed, when indicated.

BACKGROUND:The development of ST-segment elevation myocardial infarction (STEMI) in patients hospitalized for non-cardiac indications carries a high mortality rate. OBJECTIVES:Determine the impact of rural vs. urban hospital location and hospital percutaneous coronary intervention (PCI) volumes on clinical outcomes. METHODS:The New York Statewide Planning and Research Cooperative System database was queried for STEMI claims from 2011 to 2018. The 2010 Rural-Urban Commuting Area classification scheme was used to stratify hospitals as urban or rural. RESULTS:64960 STEMI patients were identified from 231 hospitals with 2880 (4.4%) being classified as inpatient STEMI (IPS). IPS patients were older (73.5 ± 13.3 years vs 64.6 ± 14.2 years; p < .0001) and more frequently female (49.3% vs 33.1%; p < .0001), had more comorbidities, were less likely to receive PCI (13.1% vs 69.4%; p < .0001), and had higher 1-year mortality (59.6% vs 16.4%; p < .0001) than outpatient STEMI (OPS). IPS that occurred in rural hospitals were less often treated with PCI (3.8% vs 13.8%; p < 0.01) and had higher one-year mortality (68.6% vs 58.9%; p < 0.01) than those occurring in urban hospitals. Similar results were observed when hospitals were divided into rural vs suburban vs urban based on the 2013 National Center for Health Statistics Urban-Rural Classification Scheme for Counties. Patients with IPS admitted to low-volume PCI centers were significantly less likely to receive PCI and had higher one-year mortality, after adjustment for demographics and comorbidities, compared to those admitted to high-volume PCI centers. CONCLUSIONS:IPS treated at rural hospitals and/or low-volume PCI centers were less likely to be treated with PCI and had higher one-year mortality rates. UNSTRUCTURED ABSTRACT:The development of ST-Segment Elevation Myocardial Infarction (STEMI) in patients hospitalized for non-cardiac indications carries a high mortality rate. Using a large retrospective cohort study, we investigated the impact of hospital location and PCI volume on outcomes in inpatient STEMI (IPS). Patients with IPS were generally older, more frequently female, and had more comorbidities than those with outpatient STEMI. After adjustment for demographics and comorbidities, those with IPS admitted to rural and/or low-volume PCI centers were less likely to receive PCI and experienced higher one-year mortality rates.

Aims BAP1‐inactivated melanocytic tumours (BIMTs) occur sporadically and in association with a familial tumour predisposition syndrome involving germline mutations in the BRCA1‐associated protein‐1 ( BAP1 ) gene. Here we report the clinical features, histopathologic findings, and chromosomal copy number data of 19 BAP1‐inactivated melanocytomas (BIMs) and compare their features to those of five BAP1‐inactivated melanomas. Methods We retrospectively searched the Department of Pathology archives and EMERSE (Electronic Medical Record Search Engine) for BIMTs that had undergone single‐nucleotide polymorphism (SNP) microarray testing. Clinical history/follow‐up data, detailed histopathologic features, and SNP microarray results were recorded. Results Overall, four patients (4/13) with BIMs and available clinical history had features suspicious for a germline BAP1 aberration. In BIMs (19 cases), the BAP1‐inactivated component showed variable cytologic features, including epithelioid (predominant), rhabdoid, plasmacytoid, and nevoid morphologies. Sentinel lymph node biopsy was negative in all (6/6) patients in which this procedure was performed. No patient diagnosed with a BIM with available clinical follow‐up (18/19; mean 38 months) experienced an adverse event. While the histologic appearances of the five melanomas varied, one case resembled a BIM. The median mitotic count was 1/mm 2 (range 0–6 mm 2 ) in BIMs compared to 3/mm 2 (range 1–4/mm 2 ) in melanomas ( P = 0.04). The median number of copy number alterations (CNAs) was two (range 0–6) in indolent cases versus seven (range 6–10) in melanomas ( P = 0.0005). The most common molecular aberration after loss of 3p21 was heterozygous loss of the CDKN2A locus, which unlike homozygous loss has not been associated with melanoma. Conclusion While most BIMs appear to have a favourable prognosis, even those with multiple CNAs, they deserve careful integration of all clinical and pathologic findings. Although not fully diagnostic, a mitotic count of ≥3/mm 2 and ≥6 CNAs in the appropriate context is supportive of a diagnosis of BAP1‐inactivated melanoma.

Primary cutaneous Ewing Sarcoma (PCES) is a rare superficial subtype of Ewing sarcoma that typically presents above the fascia and is associated with a relatively favorable prognosis compared to its deep soft tissue and osseous counterparts. This review, conducted by the American Society of Dermatopathology Appropriate Use Criteria Committee Soft Tissue Subgroup, focuses on the ancillary diagnostic methodologies for PCES. This work provides an overview of current immunohistochemical, cytogenetic, and molecular tests used to support a diagnosis of PCES. A total of 37 articles were reviewed, identifying 140 confirmed superficial cases: 26 from case reports and 114 from 10 retrospective studies (ranging from 1 to 56 cases). Immunohistochemically, CD99 demonstrated a positive membranous staining rate of 100% in PCES when reported. While NKX2.2 and PAX7 have not been widely tested in PCES, data from the broader sarcoma literature indicate NKX2.2 sensitivity ranging from 92.7% to 100%, and specificity from 85% to 87.5%. PAX7 showed sensitivity of 90% to 99% and a specificity of 83%. Molecularly, EWSR1 rearrangement by FISH was detected in 57 of 64 tested PCES cases (89%). Next-Generation Sequencing (NGS) revealed EWSR1::FLI1 rearrangement in all three tested PCES cases (100%). In conclusion, the accurate diagnosis of PCES requires a comprehensive approach, integrating detailed morphologic assessment with immunohistochemical studies and potentially cytogenetics/molecular assays.

Context.— Hypertrophic lichen planus (HLP) is a variant of lichen planus that can be difficult to diagnose based on histopathologic features alone. Thus, patient clinical history and clinicopathologic correlation are essential considerations to make the correct diagnosis. Objective.— To discuss the clinical and histologic presentation of HLP and provide a thorough review of commonly encountered mimickers in the differential diagnosis. Data Sources.— Data were derived from a literature review, personal clinical and research experiences, and a review of cases in the archives of a tertiary care referral center. Conclusions.— In general, HLP involves the lower extremities and is characterized by thickened, scaly nodules and plaques that are often pruritic and chronic in nature. HLP affects both males and females and is most common in adults 50 to 75 years of age. Unlike conventional lichen planus, HLP tends to have eosinophils and classically displays a lymphocytic infiltrate most concentrated around the tips of rete ridges. The differential diagnosis for HLP is broad and encompasses numerous entities in many different categories, including premalignant and malignant neoplasms, reactive squamoproliferative tumors, benign epidermal neoplasms, connective tissue disease, autoimmune bullous disease, infection, and drug-related reactions. Therefore, a high index of suspicion must be maintained to avoid a misdiagnosis and potential inappropriate treatments.

Leptomeningeal carcinomatosis (LMC) is a rare and fatal complication associated with various solid tumors and hematological malignancies. It presents significant diagnostic challenges due to its nonspecific symptoms and complex clinical course. This case report details the presentation, diagnosis, and implications of LMC in a 33-year-old male with a history of colorectal cancer (CRC) and hemicolectomy. The patient presented with nonspecific symptoms of headache and dizziness. Cerebrospinal fluid cytology revealed the presence of malignant cells, leading to the diagnosis of LMC secondary to CRC. The elusive and multifaceted nature of this condition highlights the necessity for increased clinical awareness and extensive research to improve the understanding and management of LMC.

Pleomorphic dermal sarcoma (PDS) is a rare cutaneous/subcutaneous neoplasm of purported mesenchymal differentiation that exists along a clinicopathologic spectrum with atypical fibroxanthoma (AFX). While PDS and AFX share histopathologic and immunohistochemical features, PDS exhibits deeper tissue invasion and has a higher rate of metastasis and local recurrence than AFX. Given its aggressive clinical course, early recognition and clinical management of PDS are essential for optimizing patient outcomes. This review aims to provide a brief overview of the clinicopathologic and molecular features, prognosis, and treatment of PDS.

ST-segment elevation myocardial infarction (STEMI) in patients hospitalized for non-cardiac indications carries a high mortality rate. The impact of hospital location on inpatient STEMI (IPS) outcomes is not well understood. We queried the New York Statewide Planning and Research Cooperative System database for all STEMI claims from 2011 to 2018 using validated ICD-9 and ICD-10 codes and classified these as outpatient STEMI (OPS) if present on admission or IPS if not present on admission. A CDC classification scheme determined by hospital Federal Information Processing Series (FIPS) code was used to stratify hospitals as urban, suburban, or rural. Comparisons were made between urban, suburban and rural hospitals among patients with IPS. A total of 61,646 STEMI patients were identified from 231 hospitals, of which 3428 (5.6%) were classified as IPS. Consistent with prior studies, IPS patients were older (72.1 ± 13.3 years vs 63.8 ± 13.7 years; p < .0001), more frequently female (46.7% vs 31.7%; p < .0001), less likely to receive percutaneous coronary intervention (PCI) (23.7% vs 74.4%; p < .0001), had more comorbidities, and had higher 30-day (43.6% vs 10.4%; p < .0001) and 1-year (53.3% vs 14.8%; p < .0001) mortality compared to OPS. IPS constituted a higher percentage of all STEMIs in rural hospitals (10.1%) than in suburban (4.4%) or urban hospitals (5.7%). IPS patients in rural hospitals, compared to suburban and urban hospitals, had a higher overall 30-day (56.2% vs 45.9% vs 42.3%) and 1-year (65.2% vs 55.2% vs 52.1) mortality and were less likely to receive PCI (10.7% vs 30.0% vs 23.3%) (p < 0.0001). Without PCI, IPS patient 30-day and 1-year mortality was also higher at rural hospitals compared to suburban or urban hospitals (30-day: 59.1% vs 57.8% vs 50.6%; 1-year: 69.2% vs 66.9% vs 61.0%; p < 0.01). IPS patients who received PCI had similar 30-day and 1-year mortality regardless of hospital location. IPS constituted a higher percentage of STEMI patients and was associated with higher 30-day and 1-year mortality in rural hospitals compared to suburban and urban hospitals. PCI was associated with better outcomes in IPS and was less frequently used in IPS patients in rural compared to suburban and urban hospitals.

The incidence of acute myocardial infarction is increasing in younger age groups, with differences in treatment and outcomes based on gender. ST-elevation myocardial infarction (STEMI) in young adults, however, is incompletely understood as most of the current studies were performed in homogenous populations, did not focus on STEMI, and lack direct comparisons with older adults. We performed a retrospective observational study using the Statewide Planning And Research Cooperative System for all admissions in New York State with a principal diagnosis of STEMI from 2011 to 2018. There were 58,083 STEMIs with the majority being male (68.2%) and non-Hispanic White (64.8%), with an average age of 63.9 ± 13.9 years. Of these, 8,494 (14.6%) occurred in patients aged <50 years. The proportion of STEMIs in women increased with age, from 19.2% in the <50-year-old age group to 48.9% in the ≥70-year-old age group. Young adults with STEMI had greater prevalence of obesity, current tobacco use, other substance use, and major psychiatric disorders, were more likely to receive revascularization, and had lower 1-year mortality than older age groups. Revascularization was associated with at least a 3 times lower odds ratio of 1-year mortality in all age groups. In conclusion, young adults with STEMI had a unique set of risk factors and co-morbidities and were more likely to undergo revascularization than older age groups. In all age groups, female gender was associated with a higher burden of co-morbidities, decreased use of revascularization, and increased 1-year mortality.

Squamoid eccrine ductal carcinoma is a rare infiltrative tumor with morphologic features intermediate between squamous cell carcinoma (SCC) and sweat gland carcinomas such as microcystic adnexal carcinoma. Although currently classified as a sweat gland carcinoma, it has been debated whether squamoid eccrine ductal carcinoma is better classified as a variant of SCC. Furthermore, therapeutic options for patients with advanced disease are lacking. Here, we describe clinicopathologic features of a cohort of 15 squamoid eccrine ductal carcinomas from 14 unique patients, with next-generation sequencing DNA profiling for 12 cases. UV signature mutations were the dominant signature in the majority of cases. TP53 mutations were the most highly recurrent specific gene alteration, followed by mutations in NOTCH genes. Recurrent mutations in driver oncogenes were not identified. By unsupervised comparison of global transcriptome profiles in squamoid eccrine ductal carcinoma (n = 7) to SCC (n = 10), porocarcinoma (n = 4), and microcystic adnexal carcinoma (n = 4), squamoid eccrine ductal carcinomas displayed an intermediate phenotype between SCC and sweat gland tumors. Squamoid eccrine ductal carcinoma displayed significantly higher expression of 364 genes (including certain eccrine markers) and significantly lower expression of 525 genes compared with other groups. Our findings support the classification of squamoid eccrine ductal carcinoma as a carcinoma with intermediate features between SCC and sweat gland carcinoma.

The conjunctiva is a thin mucous membrane covering the anterior portion of the eye. Similar to the skin, the conjunctiva has normal resident melanocytes along the basal layer of the epithelium and these cells can give rise to melanocytic neoplasms of the conjunctiva. A variety of pigmented tumors can involve the conjunctiva, ranging from benign to malignant. Given the sensitive anatomic location and potential for some conjunctival melanocytic lesions to progress to melanoma, timely clinical recognition and correct histologic diagnosis of these tumors are essential in order to initiate the appropriate treatment and optimize outcomes. Clinicopathologic correlation is a vital step in this process. In this review article, the authors aim to provide an up-to-date concise, yet detailed, summary of the clinical, histopathologic, and molecular findings as well as a brief mention of management options for each type of conjunctival melanocytic lesion that may be encountered by pathologists and dermatopathologists.

Sarcoidosis is a systemic inflammatory disorder characterized by the formation of non-caseating granulomas. Cutaneous involvement of sarcoidosis is common and has a wide variety of clinical presentations. Herein, we present a case of cutaneous sarcoidosis mimicking pigmented purpuric dermatosis (PPD) in a 26-year-old female treated with topical tofacitinib cream and a literature review of all other reported cases of cutaneous sarcoidosis with PPD-like features.

Mesenchymal tumours with melanocytic expression can pose a diagnostic challenge because they frequently demonstrate both morphological and immunohistochemical overlap with other cutaneous melanocytic neoplasms. Therefore, they present potential pathological pitfalls that may lead to a misdiagnosis of malignant melanoma. Mesenchymal neoplasms that closely mimic melanoma include malignant melanotic nerve sheath tumour (melanotic schwannoma), epithelioid schwannoma, malignant peripheral nerve sheath, cutaneous syncytial myoepithelioma, clear cell sarcoma of soft tissue, and perivascular epithelioid cell tumour. Awareness of these melanoma mimics is necessary for establishing the correct diagnosis so that the appropriate clinical management can be rendered to the patient. This in-depth review highlights key diagnostic features and molecular genetics and also discusses the differential diagnosis and treatment of mesenchymal tumours that exhibit melanocytic expression.

Basal cell carcinoma (BCC) is the most common human malignancy and is a leading cause of nonmelanoma skin cancer-related morbidity. BCC has several histologic mimics which may have treatment and prognostic implications. Furthermore, BCC may show alternative differentiation toward a variety of cutaneous structures. The vast majority of BCCs harbor mutations in the hedgehog signaling pathway, resulting in increased expression of the GLI family of transcription factors. GLI1 immunohistochemistry has been shown to discriminate between several tumor types but demonstrates high background signal and lack of specificity. In this study, we evaluated the utility of GLI1 RNA chromogenic in situ hybridization (CISH) as a novel method of distinguishing between BCC and other epithelial neoplasms. Expression of GLI1 by RNA CISH was retrospectively evaluated in a total of 220 cases, including 60 BCCs, 37 squamous cell carcinomas (SCCs) including conventional, basaloid, and human papillomavirus infection (HPV)-associated tumors, 16 sebaceous neoplasms, 10 Merkel cell carcinomas, 58 benign follicular tumors, and 39 ductal tumors. The threshold for positivity was determined to be greater than or equal to 3 GLI1 signals in at least 50% of tumor cells. Positive GLI1 expression was identified in 57/60 BCCs, including metastatic BCC, collision lesions with SCC, and BCCs with squamous, ductal, or clear cell differentiation or with other unusual features compared to 1/37 SCCs, 0/11 sebaceous carcinomas, 0/5 sebaceomas, 1/10 Merkel cell carcinomas, 0/39 ductal tumors, and 28/58 follicular tumors. With careful evaluation, GLI1 RNA CISH is highly sensitive (95%) and specific (98%) in distinguishing between BCC and nonfollicular epithelial neoplasms. However, GLI1 CISH is not specific for distinguishing BCC from most benign follicular tumors. Overall, detection of GLI1 RNA by CISH may be a useful tool for precise classification of histologically challenging basaloid tumors, particularly in the setting of small biopsy specimens, metaplastic differentiation, or metastatic disease.