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.

Undifferentiated and Dedifferentiated Metastatic Melanomas Masquerading as Soft Tissue Sarcomas: Mutational Signature Analysis and Immunotherapy Response.

The distinction between undifferentiated melanoma (UM) or dedifferentiated melanoma (DM) from undifferentiated or unclassifiable sarcoma can be difficult and requires the careful correlation of clinical, pathologic, and genomic findings. In this study, we examined the utility of mutational signatures to identify patients with UM/DM with particular attention as to whether this distinction matters for treatment because the survival of patients with metastatic melanoma has dramatically improved with immunologic therapy, whereas durable responses are less frequent in sarcomas. We identified 19 cases of UM/DM that were initially reported as unclassified or undifferentiated malignant neoplasm or sarcoma and submitted for targeted next-generation sequencing analysis. These cases were confirmed as UM/DM by harboring melanoma driver mutations, UV signature, and high tumor mutation burden. One case of DM showed melanoma in situ. Meanwhile, 18 cases represented metastatic UM/DM. Eleven patients had a prior history of melanoma. Thirteen of 19 (68%) of the tumors were immunohistochemically completely negative for 4 melanocytic markers (S100, SOX10, HMB45, and MELAN-A). All cases harbored a dominant UV signature. Frequent driver mutations involved BRAF (26%), NRAS (32%), and NF1 (42%). In contrast, the control cohort of undifferentiated pleomorphic sarcomas (UPS) of deep soft tissue exhibited a dominant aging signature in 46.6% (7/15) without evidence of UV signature. The median tumor mutation burden for DM/UM vs UPS was 31.5 vs 7.0 mutations/Mb (P < .001). A favorable response to immune checkpoint inhibitor therapy was observed in 66.6% (12/18) of patients with UM/DM. Eight patients exhibited a complete response and were alive with no evidence of disease at the last follow-up (median 45.5 months). Our findings support the usefulness of the UV signature in discriminating DM/UM vs UPS. Furthermore, we present evidence suggesting that patients with DM/UM and UV signatures can benefit from immune checkpoint inhibitor therapy.

A novel case of cutaneous myxoid spindle cell neoplasm with FMR1-ALK gene fusion and CD34/S100 co-expression.

A novel class of superficial CD34+ and S100+ cutaneous spindle cell neoplasm harboring ALK rearrangements has recently been described. Morphologically, these neoplasms have been characterized by bland spindled cells organized in whorls and cords against myxoid stroma, eventuating in the designation "superficial ALK-rearranged myxoid spindle cell neoplasm." Here, we report a 78-year-old male with a 3-mm pink papule on the chest, clinically concerning for cutaneous carcinoma. Biopsy of the specimen showed a biphasic tumor with hypercellular and hypocellular zones consisting of epithelioid cells and monomorphic, bland spindled cells. The spindled cells were arranged in perineurial-like concentric whorls and cords embedded in a myxo-collagenous stroma. Neoplastic cells were diffusely positive for CD34, S100, and D5F3-ALK, without SOX10 expression. Negative markers included GLUT1, EMA, factor XIIIa, desmin, actin, and SMA. ALK-rearrangement was identified on fluorescence in situ hybridization break-apart assay. A corresponding novel FMR1-ALK fusion was found by next-generation sequencing (NGS) based RNA sequencing. Identification of this new FMR1-ALK fusion signature adds to the spectrum of diagnostic genomic alterations in this newly described class of tumors.

Image Processing and Analysis of Mucosal Calretinin Staining to Define the Transition Zone in Hirschsprung Disease: A Pilot Study.

PURPOSE: Quantification of calretinin-stained mucosal nerve fibers by image processing and analysis (IPA) may objectively define the transition zone (TZ) of Hirschsprung disease (HD). We tested the utility of IPA as an adjunctive tool in HD. MATERIALS AND METHODS: Calretinin immunostain was performed on 15 HD pull-through specimens, and multiple images were captured from the proximal aganglionic zone, TZ, and probable normal zone (NZ). Pixel count (PC), defined as the percentage of brown-stained pixels in the mucosa, was quantified and plotted against distance from the rectal distal end. To validate the method, PCs from 45 images were compared with three-tiered visual scoring by five pathologists. Results were correlated against pertinent variables, which were retrieved from the clinical record. RESULTS: The PC gradually increased in the TZ toward the proximal resection margin in 10/13 (77%) cases. The PC variation in the probable NZ and around the circumference was substantial by the coefficient of variation. The mean PC of images with a visual score of 1 was less than scores of 2 and 3 by all five (100%) pathologists (p < 0.01). One patient had possible TZ pull-through that was clinically confirmed. CONCLUSION: While the mucosal calretinin staining gradually increases in the TZ, for now, the boundaries of the TZ cannot be accurately defined by mucosal biopsies given the substantial variation of staining around the circumference at the same distance and in the NZ. However, the IPA technique does provide a continuous variable and warrants further utility in HD studies.