Hobbs, Misty M.

AbstractBackgroundCutaneous metastases from non‐cutaneous neuroendocrine neoplasms are rare; however, distinction from primary neuroendocrine carcinomas of the skin (Merkel cell carcinoma) guides clinical management.MethodsWe performed a retrospective review from September 1, 2010 to September 30, 2020 of the histopathologic, immunohistochemical, and clinical characteristics of metastatic neuroendocrine neoplasms to the skin from non‐cutaneous primaries.ResultsFourteen patients were identified for the study (nine males and five females; mean age of 59.5 years). Fifteen skin specimens from 14 patients were available for review. At the time of skin biopsy, a known non‐cutaneous neuroendocrine neoplasm was present in 50% of patients. Primary sites of neuroendocrine carcinoma included lung (n = 5), terminal ileum (n = 2), and one each from prostate, breast, rectum, uterus, esophagus, and sinus, with one unknown (suspected bladder malignancy). Eleven of fourteen patients are dead of disease; one was lost to follow‐up. All 15 specimens showed subcutaneous/deep dermal involvement with six involving the papillary dermis and one involving the epidermis. The tumors ranged from well to poorly differentiated. Two of fifteen specimens showed focal CK20 positivity (one metastatic uterine small cell carcinoma and one metastatic ileal carcinoid). TTF‐1 was performed in 13 specimens and was positive in six, of which two were of non‐pulmonary origin.ConclusionsWhile immunohistochemical stains, in particular CK20, CK7, and TTF‐1, are integral in the workup of confirming the origin of neuroendocrine tumors found in the skin, results vary and are often non‐specific for a single primary site. Therefore, complete radiologic imaging as well as clinical correlation should be recommended to further aid in the identification of a non‐cutaneous primary neoplasm.

Polarization of tumor associated macrophages (TAMs) has been shown to have prognostic significance in different cancer types. This study evaluates the macrophage subtypes that predominates in GMF. Cases of GCTCL from 2007–2020 were identified (n = 6), clinical data was extracted from the electronic medical record, and all pathology slides were reviewed to confirm the diagnosis. Immunohistochemistry (IHC) studies were performed to characterize M1 and M2 macrophage polarization. CD68 (PGM1), pSTAT1, and CD163 were used as pan macrophage, M1, and M2 markers, respectively. The macrophages with positive staining at hot spot per high power field were counted and recorded for data analysis. The average age of patients was 60.5 years [range, 21–78], five patients (83%) were women and 1 (17%) was a man. Five patients were Caucasian (83%), and 1 was Black/African American (17%). Two patients had late stage GMF with M2 (CD163) predominance and the other three had early stage GMF with M1 (pSTAT1) predominance. Our study suggests that macrophage polarization present in GMF tends to be M1 in early stages and M2 in advanced stages. Additional studies are needed to further elucidate the microenvironment of macrophages present in GMF. Such findings may lead to prognostic and therapeutic advances in GMF.

Abstract Pyoderma gangrenosum (PG) lacks consensus regarding treatment, and no prior studies assess treatment satisfaction in PG. The objective of this study was to determine patient‐reported satisfaction in the treatment of PG, and associations with satisfaction. Methodology was a multicenter cross‐sectional survey for patients who received systemic medication(s) to treat PG. Thirty‐five patients completed the survey (mean age: 54.0 years, 65.7% female, response rate: 81.4%). Mean (± SD) SATMED‐Q score was 75.0 (±16.2, range: 67.6‐85.3). Older patients (72.6 ± 23.6 for 18‐39 years, 74.4 ± 16.1 for 40‐59, 77.1 ± 11.6 for 60+), plus those with higher incomes (72.9 ± 20.3 for $0‐49 000; 74.0 ± 17.6 for $50 000‐99 000; 79.0 ± 14.6 for $100 000+) and education status (69.4 ± 14.3 for high school equivalent, 72.9 ± 15.9 for undergraduate, 91.7 ± 10.6 for graduate), were more satisfied with treatment. Ulcerative PG had higher SATMED‐Q scores (79.0 ± 13.2) than other subtypes (66.2 ± 19.3). For local therapy, wound care, or pain control, 63.2%, 100%, and 75% were satisfied, respectively. The mean DLQI was 8.6 (±7.6, range: 0‐29), and higher DLQI was associated with decreased satisfaction. Satisfaction with providers was positively correlated with global satisfaction (Pearson's r = 0.638). The presence of pain and/or depression influenced both SATMED‐Q (72.8 ± 18.8 with pain, 78.3 ± 11.2 without; 68.2 ± 18.8 with depression, 80.1 ± 12.2 without) and DLQI scores (12.1 ± 8.1 with pain, 3.9 ± 3.4 without; 10.3 ± 7.1 with depression, 7.4 ± 8.0 without). To optimize the patient experience, non‐modifiable associations should be individually considered, and potentially modifiable associations such as satisfaction with specific providers, pain, and depression, may be targeted for management.

Abstract Pyoderma gangrenosum (PG) is a rare disease of unknown aetiology, first described over a century ago. Initially thought to have an infectious cause, and now primarily considered an autoinflammatory condition, PG continues to be poorly understood, commonly misdiagnosed, and difficult to treat. In this review, we discuss the journey of our understanding of PG to date, including first descriptions, challenges with diagnosis, presumed pathogenesis, and treatments used. We highlight major historical landmarks and their importance, explain the rationale behind current investigations, note outstanding gaps in knowledge, and explore the future directions of PG research. We summarise what we have known, what we are working on knowing, and what we have yet to explore about PG, illustrating overall trends to invigorate future research.