Syphilis has many atypical morphologies which can present a diagnostic challenge, especially in patients with HIV/AIDS who may have multiple concurrent conditions. We describe a 41-year-old man with recently diagnosed HIV who was admitted for acute right vision loss and a diffuse rash with involvement of the palms and soles. He received diagnoses of secondary syphilis and Kaposi sarcoma in the setting of AIDS. Examination revealed an unusual dark brown-to-purple umbilicated papule with a necrotic center on the abdomen, raising a diagnostic dilemma. Skin biopsy showed secondary syphilis, despite the concurrent diagnosis of Kaposi sarcoma. The patient was treated with antibiotic and antiretroviral therapy and symptoms resolved. This case aims to share the clinical reasoning behind diagnosing a patient with HIV/AIDS with multiple concurrent conditions and to raise awareness of the many atypical cutaneous manifestations of secondary syphilis.

Importance

Classic calciphylaxis associated with renal failure is a life-threatening disease. Warfarin-associated calciphylaxis without renal injury has been described, but whether it is a subset of classic calciphylaxis or a different entity remains unknown. We describe 1 case of warfarin-associated calciphylaxis, present data from 2 others from our institution, and review all cases of warfarin-associated calciphylaxis available in the literature. Our review indicates that warfarin-associated calciphylaxis is clinically and pathophysiologically distinct from classic calciphylaxis.

Objective

To review warfarin-associated calciphylaxis and determine its relationship to classic calciphylaxis.

Design, setting, and participants

We searched MEDLINE and Ovid without language or date restrictions for case reports of calciphylaxis from the inpatient setting using the terms "calciphylaxis and warfarin," "non-uremic calciphylaxis," and "nonuremic calciphylaxis." We defined nonuremic calciphylaxis as a histopathologic diagnosis of calciphylaxis without severe kidney disease (serum creatinine level >3 mg/dL; glomerular filtration rate <15 mL/min; acute kidney injury requiring dialysis; and renal transplantation).

Exposures

Each patient had been exposed to warfarin before the onset of calciphylaxis.

Main outcomes and measures

Patient data were abstracted from published reports. Original patient medical records were requested and reviewed when possible.

Results

We identified 18 patients with nonuremic calciphylaxis, 15 from the literature, and 3 from our institution. Patients were predominantly female (15 of 18 [83%]) with ages ranging from 19 to 86 years. Duration of warfarin therapy prior to calciphylaxis onset averaged 32 months. Lesions were usually located below the knees (in 12 of 18 [67%]). No cases reported elevated calcium-phosphate products (0 of 17 [0%]). Calcifications were most often noted in the tunica media (n = 8 [44%]) or in the vessel lumen and tunica intima (n = 7 [39%]). The most common treatments included substitution of heparin or low-molecular weight heparin for warfarin (n = 13 [72%]), intravenous sodium thiosulfate (n = 9 [50%]), and hyperbaric oxygen (n = 3 [17%]). The survival rate on hospital discharge was remarkably high, with 15 cases (83%) reporting full recovery and 3 cases ending in death.

Conclusions and relevance

Warfarin-associated calciphylaxis is distinct from classic calciphylaxis in pathogenesis, course, and, particularly, outcome. This finding should influence clinical management of the disease and informs targeted treatment of the disease.

Importance

Mycosis fungoides and Sézary syndrome (MF/SS) are rare in children and young adults, and thus the incidence and outcomes in this patient population are not well studied.

Objective

To assess the incidence and outcomes of MF/SS in patients diagnosed before 30 years of age.

Design, setting, and participants

Retrospective study of 2 population-based cancer registries-the California Cancer Registry (n = 204) and 9 US cancer registries of the Surveillance, Epidemiology, and End Results program (SEER 9; n = 195)-for patients diagnosed with MF/SS before 30 years of age.

Main outcomes and measures

Overall survival was calculated by the Kaplan-Meier method. The risk of a second cancer was assessed by calculating the standard incidence ratio (SIR) comparing observed cancer incidence in patients with MF/SS with the expected incidence in the age-, sex-, and race-standardized general population.

Results

The incidence of MF/SS is rare before 30 years of age, with an incidence rate of 0.05 per 100,000 persons per year before age 20 years and 0.12 per 100,000 persons per year between ages 20 and 29 years in the California Cancer Registry. At 10 years, patients with MF/SS had an overall survival of 94.3% (95% CI, 89.6%-97.2%) in the California Cancer Registry and 88.9% (95% CI, 82.4%-93.2%) in SEER 9. In SEER 9, there was a significant excess risk of all types of second cancers combined (SIR, 3.40; 95% CI, 1.55-6.45), particularly lymphoma (SIR, 12.86; 95% CI, 2.65-37.59) and melanoma (SIR, 9.31; 95% CI, 8.75-33.62). In the California Cancer Registry, the SIR for risk of all types of second cancers was similar to that in SEER 9 (SIR, 3.45; 95% CI, 0.94-8.83), although not statistically significant.

Conclusions and relevance

Young patients with MF/SS have a favorable outcome, despite a strong suggestion of an increased risk of second primary cancers. Prolonged follow-up is warranted to definitively assess their risk of developing second cancers in a lifetime.

Importance

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare malignant neoplasm with cutaneous manifestations and a rapidly progressive clinical course. The diagnosis relies on characteristic clinicopathologic and immunopathologic features. However, the overlap of immunophenotypic features with other cancers, as well as newly discovered interpersonal and intrapersonal phenotypic variations, renders the identification of BPDCN challenging. A greater understanding of the proteins expressed by BPDCN might facilitate its recognition and provide insights into its clinical behavior.

Observations

In 7 of 9 patients at 4 tertiary care institutions, immunohistochemical analysis demonstrated strong CD31/PECAM-1 (platelet endothelial cell adhesion molecule 1) expression by neoplastic cells. Combined with similar findings observed in 1 former patient, 8 of 10 cases of BPDCN were CD31/PECAM-1 positive.

Conclusions and relevance

Expression of CD31/PECAM-1 by BPDCN adds new information about the antigenic profile of this unusual neoplasm. CD31/PECAM-1 influences multiple cell functions including adhesion, apoptosis, coagulation, host response, and protein synthesis that might affect clinical features of BPDCN such as hemorrhage, aggressive tumor growth, and resistance to therapy. Therefore, the potential role of this molecule in the tumor formation and progression of BPDCN warrants additional exploration.

Melanomas that have histopathologic features that overlap with those of Spitz nevus are referred to as spitzoid melanomas. However, the diagnostic concept is used inconsistently and genomic analyses suggest it is a heterogeneous category. Spitz tumors, the spectrum of melanocytic neoplasms extending from Spitz nevi to their malignant counterpart Spitz melanoma, are defined in the 2018 WHO classification of skin tumors by the presence of specific genetic alterations, such as kinase fusions or HRAS mutations. It is unclear what fraction of "spitzoid melanomas" defined solely by their histopathologic features belong to the category of Spitz melanoma or to other melanoma subtypes. We assembled a cohort of 25 spitzoid melanomas diagnosed at a single institution over an 8-year period and performed high-coverage DNA sequencing of 480 cancer related genes. Transcriptome wide RNA sequencing was performed for select cases. Only nine cases (36%) had genetic alterations characteristic of Spitz melanoma, including HRAS mutation or fusion involving BRAF, ALK, NTRK1, or MAP3K8. The remaining cases were divided into those with an MAPK activating mutation and those without an MAPK activating mutation. Both Spitz melanoma and spitzoid melanomas in which an MAPK-activating mutation could not be identified tended to occur in younger patients on skin with little solar elastosis, infrequently harbored TERT promoter mutations, and had a lower burden of pathogenic mutations than spitzoid melanomas with non-Spitz MAPK-activating mutations. The MAPK-activating mutations identified affected non-V600 residues of BRAF as well as NRAS, MAP2K1/2, NF1, and KIT, while BRAF V600 mutations, the most common mutations in melanomas of the WHO low-CSD category, were entirely absent. While the "spitzoid melanomas" comprising our cohort were enriched for bona fide Spitz melanomas, the majority of melanomas fell outside of the genetically defined category of Spitz melanomas, indicating that histomorphology is an unreliable predictor of Spitz lineage.

Primary cutaneous CD8-positive aggressive epidermotropic T-cell lymphoma is a rare and poorly characterized variant of cutaneous lymphoma still considered a provisional entity in the latest 2016 World Health Organization Classification of Cutaneous lymphomas. We sought to better characterize and provide diagnostic and therapeutic guidance of this rare cutaneous lymphoma. Thirty-four patients with a median age of 77 years (range 19-89 years) presented primarily with extensive annular necrotic plaques or tumor lesions with frequent mucous membrane involvement. The 5-year survival was 32% with a median survival of 12 months. A subset of 17 patients had a prodrome of chronic patches prior to the development of aggressive ulcerative lesions. We identified cases with lack of CD8 or αβ T-cell receptor expression yet with similar clinical and pathological presentation. Allogeneic stem cell transplantation provided partial or complete remissions in 5/6 patients. We recommend the term primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphoma as this more broad designation better describes this clinical-pathologic presentation, which allows the inclusion of cases with CD8 negative and/or αβ/γδ T-cell receptor chain double-positive or double-negative expression. We have identified early skin signs of chronic patch/plaque lesions that are often misdiagnosed as eczema, psoriasis, or mycosis fungoides. Our experience confirms the poor prognosis of this entity and highlights the inefficacy of our standard therapies with the exception of allogeneic stem cell transplantation in selected cases.