Clinically amyopathic dermatomyositis: Clinical, laboratory, and histopathological features.

BACKGROUND: Despite the advancements in the categorization of clinically amyopathic dermatomyositis (CADM), the classification and diagnosis of its subtypes are still challenging. The aim of our study was to describe the clinicopathological features of CADM and assess the differences between amyopathic dermatomyositis (ADM) and hypomyopathic dermatomyositis (HDM). METHODS: This retrospective study included 43 patients with CADM diagnosed at our institution from 2016 to 2020. Patients were subclassed into ADM (n = 30) and HDM (n = 13) groups to assess their clinicopathological differences. RESULTS: All included patients had characteristic cutaneous manifestations of dermatomyositis; 67.4% had myositis-associated auto-antibodies, including ANA (32.6%), RNP (14.0%), anti-Ro52 (9.3%), anti-p155/140 (7.0%), rheumatoid factor (7.0%), anti-NXP-2 (4.7%), anti-MDA5 (2.3%), and anti-Jo-1 (2.3%) antibodies. One patient had associated interstitial lung disease, and another patient had oral squamous cell carcinoma. The histopathological findings included mucin deposition (69.8%), telangiectasia (65.1%), lymphocytic infiltrate (48.8%), vacuolar interface dermatitis (46.5%), and epidermal atrophy (14.0%). Compared to patients with HDM, ADM patients were significantly less likely to have epidermal atrophy, 3.3% versus 38.5% (p = 0.006), and more likely to have mucin deposition, 80.0% versus 46.2% (p = 0.028). CONCLUSION: We described the clinicopathological features of CADM and highlighted the distinctions between ADM and HDM dermatopathologic findings. This information may prove helpful in diagnosing ambiguous lesions.

H2A.Z chaperones converge on E2F target genes for melanoma cell proliferation.

High levels of H2A.Z promote melanoma cell proliferation and correlate with poor prognosis. However, the role of the two distinct H2A.Z histone chaperone complexes SRCAP and P400-TIP60 in melanoma remains unclear. Here, we show that individual subunit depletion of SRCAP, P400, and VPS72 (YL1) results in not only the loss of H2A.Z deposition into chromatin but also a reduction of H4 acetylation in melanoma cells. This loss of H4 acetylation is particularly found at the promoters of cell cycle genes directly bound by H2A.Z and its chaperones, suggesting a coordinated regulation between H2A.Z deposition and H4 acetylation to promote their expression. Knockdown of each of the three subunits downregulates E2F1 and its targets, resulting in a cell cycle arrest akin to H2A.Z depletion. However, unlike H2A.Z deficiency, loss of the shared H2A.Z chaperone subunit YL1 induces apoptosis. Furthermore, YL1 is overexpressed in melanoma tissues, and its upregulation is associated with poor patient outcome. Together, these findings provide a rationale for future targeting of H2A.Z chaperones as an epigenetic strategy for melanoma treatment.

Cutaneous Syncytial Myoepithelioma: An Uncommon and Distinct Variant of Cutaneous Epithelioid Neoplasm.

BACKGROUND: Cutaneous syncytial myoepithelioma (CSM) is an uncommon and distinct variant of cutaneous myoepithelioma. We aim to present a case of CSM to enhance the recognition of this unique variant, encompassing its clinical characteristics, histopathological features, immunohistochemical staining, and therapeutic approaches. CASE PRESENTATION: A 10-year-old girl presented with a dome-shaped nodule located on the skin of her left medial distal arm. Microscopic examination of the skin biopsy revealed a well-defined dermal nodular lesion, surrounded by an epidermal collarette. Tumor cells were composed of epithelioid to spindle-shaped cells with round-to-oval nuclei, small nucleoli, and abundant eosinophilic cytoplasm with a syncytial-like growth pattern. A moderate degree of nuclear pleomorphism was noted. Mitotic activity was not prominent. Immunohistochemical staining revealed positive staining for epithelial membrane antigen, GLUT1, collagen IV, and S100. Smooth muscle actin, CD10, and CD68 showed patchy positivity. CD31, CD34, p63, SOX10, anaplastic lymphoma kinase (ALK), glial fibrillary acidic protein, pankeratin (AE1/AE3/PCK26), Melan-A, and CD1a were negative. Fluorescence in situ hybridization targeting TFE3 and ALK genes was negative. The differential diagnosis included ALK-negative epithelioid cell histiocytoma, epithelioid perineurioma, and CSM. Based on the above findings, a diagnosis of CSM was rendered. DISCUSSION: CSM is a benign cutaneous neoplasm composed of sheets of histiocytoid or short spindle cells with pale eosinophilic cytoplasm with a syncytial-like growth pattern. Clinically, CSM often presents as a painless, slow-growing nodule or plaque in a broad anatomical distribution with a preference for the distal extremities.. CSM is characteristically positive for epithelial membrane antigen (EMA) and S100 protein and negative for keratins. In challenging cases, molecular testing for EWSR1 gene rearrangement and EWSR1-PBX3 gene fusion aid in confirming the diagnosis. CONCLUSIONS: The histologic features of CSM present a unique set of challenges posing a diagnostic dilemma, as they can bear resemblance to a range of benign and malignant cutaneous neoplasms including ALK-negative epithelioid cell histiocytoma, epithelioid perineurioma, malignant or nevoid melanoma, and epithelioid sarcoma. An accurate diagnosis is crucial for guiding proper clinical management considering that this entity typically demonstrates an excellent prognosis following a complete surgical excision.

H2A.Z chaperones converge on histone H4 acetylation for melanoma cell proliferation.

High levels of H2A.Z promote melanoma cell proliferation and correlate with poor prognosis. However, the role of the two distinct H2A.Z histone chaperone complexes, SRCAP and P400-TIP60, in melanoma remains unclear. Here, we show that individual depletion of SRCAP, P400, and VPS72 (YL1) not only results in loss of H2A.Z deposition into chromatin, but also a striking reduction of H4 acetylation in melanoma cells. This loss of H4 acetylation is found at the promoters of cell cycle genes directly bound by H2A.Z and its chaperones, suggesting a highly coordinated regulation between H2A.Z deposition and H4 acetylation to promote their expression. Knockdown of each of the three subunits downregulates E2F1 and its targets, resulting in a cell cycle arrest akin to H2A.Z depletion. However, unlike H2A.Z deficiency, loss of the shared H2A.Z chaperone subunit YL1 induces apoptosis. Furthermore, YL1 is overexpressed in melanoma tissues, and its upregulation is associated with poor patient outcome. Together, these findings provide a rationale for future targeting of H2A.Z chaperones as an epigenetic strategy for melanoma treatment.

Cutaneous Aspergilloma Caused by Aspergillus niger in an Immunocompetent Patient.

An 82-year-old man presented with a growth on his scalp for 7 months. It was increasing in size despite treatment with a variety of shampoos and systemic plus topical antibiotics. It was pruritic with a burning sensation. Lately, the patient had a body weight loss of 35 pounds. Extensive work-ups for malignancy included computerized axial tomography (CAT) and examinations of the gastrointestinal and respiratory tracts; however, no etiology for this weight loss was established. This was not thought to be directly related to the scalp lesion. Work-ups for any infectious etiology, including blood cultures, were proven to be noncontributory. His past medical included chronic obstructive pulmonary disease and gastritis. He also patient had a long history of tobacco use.

Cutaneous Atypical Fibroxanthoma With Osteoclast-Like Giant Cell: A Rare but Diagnostic Pitfall.

BACKGROUND: Atypical fibroxanthoma (AFX) is a dermal-based, low-grade neoplasm with no specific lineage of differentiation. The occurrence of AFX with osteoclast-like giant cells is exceptionally rare. Less than 20 cases have been reported in the literature. CASE PRESENTATION: A 77-year-old man with a medical history of multiple basal and squamous cell carcinomas of the skin, presented with a progressively growing erythematous nodule on the sun-damaged right central parietal scalp. A shave biopsy showed a dermal spindle cell proliferation accompanied by numerous osteoclast-like multinucleated giant cells and predominant atypical mitotic figures. The immunohistochemical staining showed a diffuse positive staining for CD68 and SMA, patchy staining for CD10, and negative staining for SOX-10, pan-cytokeratin, CK5/6, S100, CD34, and desmin. The tumor was completely excised with negative margins. A subsequent follow-up over a period of 13 months showed no recurrence. CONCLUSION: Distinguishing AFX with osteoclast-like giant cells from both malignant and benign skin lesions with osteoclast-like giant cells is crucial. Although AFX tumors display worrisome malignant histologic features, most cases have a favorable prognosis with a local recurrence rate below 5% and exceedingly rare metastasis.

HTLV-1 Presenting as an Incidental Finding after a Cosmetic Procedure.

A 44-year-old woman presented to a plastic surgeon for liposuction of the abdomen, back, and flanks, a gluteal fat transfer, and a vertical pattern breast lift and small reduction. The patient had a medical history of significantly well-controlled hypertension for 4 years treated with hydrochlorothiazide and amlodipine. She had been pregnant four times and delivered six children with two sets of twins. She was allergic to latex and denied a history of smoking. Her physical examination was unremarkable and her body mass index (BMI) was 26.1. No skin lesions were evident (Figure 1). Her preoperative laboratory findings were within normal limits, with unremarkable electrocardiogram (EKG), chest x-ray, and mammogram. The patient underwent a successful surgical procedure, and the excised breast tissue and skin were sent to pathology for routine evaluation. Surgery removed 220 g of breast tissue from the left breast and 45 g was excised from the right one. The histopathology depicted atypical T-cells in the epidermis and superficial dermis of both left and right breasts. Physical examination failed to evidence lymph-adenopathy or masses. The patient denied weight loss, night sweats, or fever; however, due to her Caribbean heritage, adult T-cell leukemia/ lymphoma was considered and submitted for further histologic workup.

Halogen halos: Report of an early histopathologic finding in iododerma.

Iododerma is a rare cutaneous eruption that manifests after exposure to iodine-containing compounds, with few cases reported in the literature. Previous reports of this halogenoderma have described acellular halos simulating cryptococcus on histopathological examination but there is a paucity of reports of biopsies taken early in the disease course. We present a case of a 78-year-old patient who developed a papular eruption after receiving iodinated contrast. A skin biopsy taken within 24 h of the eruption showed a neutrophilic infiltrate with cryptococcal-like acellular haloed structures, indicating that the diagnostic finding may be found early in the disease course.