NUT Expression Is of Diagnostic Utility in the Distinction of Digital Papillary Carcinoma From Poroid Hidradenoma.

ABSTRACT: The distinction between digital papillary adenocarcinoma (DPAC) and benign cutaneous adnexal tumors is clinically important and can be challenging. Poroid hidradenoma frequently occurs at acral sites and can show a number of histological features, which overlap with digital papillary adenocarcinoma. Recent work has shown that YAP1-NUTM1 fusions are frequent in poroid hidradenoma and are associated with nuclear protein in testis (NUT) expression by immunohistochemistry. We evaluated the expression of NUT-1 by immunohistochemistry in 4 cases of DPAC and 4 cases of poroid hidradenoma. Three of 4 cases of poroid hidradenoma showed strong NUT-1 expression, with no staining in any of the cases of DPAC. These results suggest that NUT-1 immunohistochemistry may be a useful additional tool in evaluating this differential diagnosis.

Adult onset xanthogranuloma of the eyelid.

Purpose: To report a rare case of an eyelid lesion in an adult, with histological features of juvenile xanthogranuloma (JXG). Observations: Juvenile xanthogranuloma primarily affects the skin of infants and young children. It infrequently can involve the structures of the eye and orbit and rarely occurs in individuals beyond the second decade of life. We present a case of adult onset xanthogranuloma (AXG) involving the eyelid of a 29-year-old female. This lesion required management with multiple treatment modalities. Conclusions: This is a rare example of an eyelid xanthogranuloma in an adult. As such, JXG-like lesions should be included as a differential diagnosis for lesions of the eye and orbit in adults. Surgical management may be required if there is no response to intralesional steroids.

Transient cryoglobulinaemic vasculitis following ChAdOx1 nCoV-19 vaccine.

Cryoglobulinaemic vasculitis is an immune-complex-mediated, systemic inflammatory syndrome usually involving small-to-medium vessels due to precipitation of cryoglobulins at <37°C. It can involve any organ but most commonly affects the skin. Associated conditions include infections (hepatitis C and HIV), haematological disorders (chronic lymphocytic lymphoma, monoclonal gammopathy of uncertain significance and multiple myeloma), autoimmune conditions (systemic lupus erythematosus and Sjogren syndrome) or as a complication following vaccination (influenza, pneumococcal and hepatitis B vaccines). Biochemical hallmarks include detection of serum cryoglobulin with low C4 levels. We describe a case of previous healthy patient with transient cryoglobulinaemic vasculitis after first dose of ChAdOx1 nCoV-19 vaccine (AstraZeneca/Oxford).

Intra- and intertumoral heterogeneity of liver metastases in a patient with uveal melanoma revealed by single-cell RNA sequencing.

Tumor heterogeneity is a major obstacle to the success of cancer treatment. An accurate understanding and recognition of tumor heterogeneity is critical in the clinical management of cancer patients. Here, we utilized single-cell RNA sequencing (scRNA-seq) to uncover the intra- and intertumoral heterogeneity of liver metastases from a patient with metastatic uveal melanoma. The two metastases analyzed were largely infiltrated by noncancerous cells with significant variability in the proportion of different cell types. Analysis of copy-number variations (CNVs) showed gain of 8q and loss of 6q in both tumors, but loss of Chromosome 3 was only detected in one of the tumors. Single-nucleotide polymorphism (SNP) array revealed a uniparental isodisomy 3 in the tumor with two copies of Chromosome 3, indicating a regain of Chromosome 3 during the development of the metastatic disease. In addition, both tumors harbored subclones with additional CNVs. Pathway enrichment analysis of differentially expressed genes revealed that cancer cells in the metastasis with isodisomy 3 showed up-regulation in epithelial-mesenchymal transition and myogenesis related genes. In contrast, up-regulation in interferon signaling was observed in the metastasis with monosomy 3 and increased T-cell infiltrate. This study highlights the complexity and heterogeneity of different metastases within an individual case of uveal melanoma.

Genome wide methylation profiling of selected matched soft tissue sarcomas identifies methylation changes in metastatic and recurrent disease.

In this study we used the Illumina Infinium Methylation array to investigate in a cohort of matched archival human tissue samples (n = 32) from 14 individuals with soft tissue sarcomas if genome-wide methylation changes occur during metastatic and recurrent (Met/Rec) disease. A range of sarcoma types were selected for this study: leiomyosarcoma (LMS), myxofibrosarcoma (MFS), rhabdomyosarcoma (RMS) and synovial sarcoma (SS). We identified differential methylation in all Met/Rec matched samples, demonstrating that epigenomic differences develop during the clonal evolution of sarcomas. Differentially methylated regions and genes were detected, not been previously implicated in sarcoma progression, including at PTPRN2 and DAXX in LMS, WT1-AS and TNXB in SS, VENTX and NTRK3 in pleomorphic RMS and MEST and the C14MC / miR-379/miR-656 in MFS. Our overall findings indicate the presence of objective epigenetic differences across primary and Met/Rec human tissue samples not previously reported.

Conjunctival Stromal Tumor: Report of 2 New Cases and Review of the Literature.

Conjunctival stromal tumor (COST) is an emerging entity with only a limited number of cases reported in the literature. In this report, we describe 2 additional cases, review the accumulative clinical and histopathological features and expand on the immunophenotypic property of this entity. COST appears to have a sporadic presentation, affecting both sexes and patients of variable ethnicity and age group and predominantly occurring on the bulbar conjunctiva as a slow-growing asymptomatic or slightly tender mass-like lesion. Histopathologically, COST is characterized by singly dispersed spindle to round cells, often with some degree of degenerative nuclear atypia, within a myxomatous to collagenous stroma. Lesional cells are characteristically positive for CD34 and vimentin, negative for S100, SOX10 and STAT6 and show a normal pattern of staining with RB1 by immunohistochemistry. The reported cases to date have shown an indolent biological behavior, reliably treated by a complete surgical excision.

Histiocytoid Melanoma.

While most melanomas display well-characterised and readily recognised architectural and cytomorphological features, unusual variants can create diagnostic difficulties. Variants which mimic benign or reactive processes are particularly problematic. We report 5 cases of melanoma characterised by a subtle microscopic appearance reminiscent of a benign dermal histiocytic infiltrate, which we refer to as "histiocytoid melanoma." These lesions are characterised clinically by ill-defined areas of cutaneous pigmentation, which in several cases reached large proportions. Microscopically, there is a subtle interstitial pattern of infiltration by predominantly single cells with a histiocytoid morphology, often resembling melanophages. Immunohistochemical confirmation was typically required, with the cells showing positive labelling for Sox-10 as well as Melan-A. In several examples, the proliferation extended to clinically uninvolved surgical margins, necessitating multiple excisions, and many of our patients have experienced locoregional recurrence. However, none have developed distant metastases or died of melanoma. While uncommon, this subtle variant is important to recognise in order to ensure adequate histological clearance is obtained.

Pseudomelanomas Following Stevens-Johnson Syndrome.

In this report, we present a novel case of pseudomelanoma, similar to that seen in a recurrent/traumatized nevus, in pre-existing nevi in a 36-year-old man a few months after recovering from an episode of severe Stevens-Johnson syndrome. The mechanism responsible for the atypical transformation of these nevi is likely the release of cytokines and growth factors in the microenvironment during the repair/regeneration process. It is important to be aware of this phenomenon, and specific inquiry about potential recent blistering skin disorder in addition to the other causes of trauma should be made when dealing with cases of pseudomelanoma to avoid misdiagnosis.

Metastatic Cellular Blue Nevus: A Rare Case With Metastasis Beyond Regional Nodes.

In this study, we present a rare case of a 35-year-old man with a long-standing blue-black lesion on his left hand with subsequent infraclavicular and axillary lymph node tumor deposits. The hand lesion and lymph nodes were excised revealing histological, immunohistochemical, and molecular findings consistent with cellular blue nevus. Despite nonregional lymph node involvement, there has been no progression at 12-months follow-up. This is an index case of a cellular blue nevus with metastasis to both regional and nonregional lymph nodes. The lack of atypical/malignant features in this lesion makes the metastatic behavior extraordinary, and hence the prognosis of lesions of this type is indeterminate.

Detection of Epidermal Growth Factor Receptor Mutations in Lung Adenocarcinoma: Comparing Cobas 4800 EGFR Assay With Sanger Bidirectional Sequencing.

INTRODUCTION: Accurate detection of epidermal growth factor receptor (EGFR) mutations has a crucial role in the current treatment of patients with lung adenocarcinoma, and identification of clinically relevant mutations would qualify patients for treatment with tyrosine kinase inhibitors. Historically, Sanger sequencing has been used as the reference standard assay for EGFR mutational analysis; however, Cobas 4800 is a relatively new method. In the present study, we compared the performance of the Cobas assay against that of Sanger sequencing. MATERIALS AND METHODS: A total of 493 consecutive formalin-fixed paraffin-embedded samples of lung adenocarcinoma were simultaneously tested for EGFR mutations using both methods. RESULTS: After exclusion of the invalid results (n = 19), 474 samples from 455 patients were analyzed. The Cobas assay showed a mutation detection rate comparable to that of Sanger sequencing (18.1% vs. 17.9%, respectively; P < .05). Excellent agreement of 98.9% (κ, 0.964) was observed between the 2 methods. CONCLUSION: The Cobas assay is a fast and diagnostically robust platform with high analytical sensitivity; however, it is limited by its detection range and low tolerance to low DNA quality. Sanger sequencing is mostly affected by its lower analytic sensitivity. Ultimately, a dual testing strategy will be justified to increase the detection of novel mutations and reduce the false-negative results within an acceptable turnaround time.

Malignant Melanocytic Matricoma: A Report of 2 Cases and Review of the Literature.

BACKGROUND: To describe 2 cases of melanocytic matricoma with malignant histological features and systematically review previously reported cases of malignant melanocytic matricoma. METHODS: Two cases of malignant melanocytic matricoma were identified from the practice of the authors. Additional 3 cases were identified in the literature. The clinical and pathological features of these 5 cases are described. RESULTS: Malignant melanocytic matricoma occurs predominantly in sun-damaged skin of elderly individuals. The tumor is composed of atypical epithelial cells with brisk mitotic activity showing evidence of matrical keratinization and widespread positivity with beta-catenin. There is an admixed cytologically bland dendritic melanocytic component. To date, local recurrence has occurred in one case, but no cases of disseminated disease or death have been reported. CONCLUSIONS: Recognition of this rare tumor and separation from a range of diagnostic mimics is important to ensure adequate treatment by local excision and to allow further cases to be identified to better define the biological potential of this lesion.

Extramedullary hematopoiesis associated with organizing peritoneal hemorrhage: a report of 5 cases in patients presenting with primary gynecologic disorders.

Extramedullary hematopoiesis (EMH) usually occurs in patients with severe anemia or myelofibrosis, and involvement of the serous cavities is uncommon. A total of 5 cases of peritoneal EMH are presented in patients presenting with primary gynecologic pathology including endometrial adenosarcoma (n=2), ovarian leiomyosarcoma, and ovarian endometrioid adenocarcinoma (each n=1), all of which were associated with peritoneal metastases; the remaining patient had a hemorrhagic benign ovarian cyst. All cases were associated with organizing peritoneal hemorrhage, and EMH was localized to the reactive granulation tissue. EMH was not identified within the tumor tissue in the 4 neoplastic cases. Erythroid precursors were present in all cases and granulocytic precursors and megakaryocytes were identified in two and three cases, respectively. There was no evidence of EMH in the corresponding peritoneal fluid cytology preparations examined in 4 cases. None of the patients had a significant hematological abnormality at the time of presentation or during a mean follow-up period of 35 mo (range, 2-66 mo). The mechanism of peritoneal EMH in these cases is uncertain but most likely related to tissue hemorrhage and repair as described in other sites such as dura, myocardium, and synovium. Pathologists should be aware that EMH may involve the peritoneum to avoid misinterpretation of the findings, particularly in small biopsy or cytology samples.