Review of our cases and the published literature suggests that the diagnosis of malignant PTT be given to PTT showing a combination of non-scalp location, recent rapid growth, size greater than 5 cm, infiltrative growth, and significant cytologic atypia with mitotic activity. At the present time the stratification of malignant PTT into low- and high-grade categories is not possible.
Human herpesvirus-8 (HHV-8) latency-associated nuclear antigen (LANA) is expressed in endothelial and spindle cells of nearly all Kaposi sarcomas, and the presence of this antigen in serum is strongly correlated with the risk of developing Kaposi sarcoma in immunocompromised individuals. Studies of vascular tumors occurring in the general population show LANA expression to be specific for Kaposi sarcoma. No study to date, however, has examined whether non-Kaposi sarcoma vascular tumors arising in immunocompromised patients may express LANA, possibly reflecting origin from an HHV-8-infected endothelial progenitor cell. The objective of this study was to evaluate the specificity of LANA expression for Kaposi sarcoma in immunocompromised patients by LANA immunohistochemistry and real-time polymerase chain reaction (PCR) for HHV-8. A total of 13 cases of non-Kaposi sarcoma vascular tumors (12 hemangiomas and one epithelioid hemangioendothelioma) and 24 cases of Kaposi sarcoma, all from known HIV-positive patients, were immunostained for LANA and evaluated for the presence of HHV-8 DNA by real-time PCR. LANA expression was seen in 22 of 24 (92%) of Kaposi sarcoma cases and in 0 of 13 non-Kaposi sarcoma cases. Real-time PCR detected HHV-8 in all of the Kaposi sarcoma cases and in four of the non-Kaposi sarcoma cases (all hemangiomas). LANA expression appears to be a highly sensitive and specific marker of Kaposi sarcoma in both the general population and in HIV-positive patients. This is in contrast to HHV-8 PCR, which is positive in a small subset of non-Kaposi sarcoma vascular tumors, most likely due to detection of HHV-8 within intratumoral blood mononuclear cells by the highly sensitive real-time PCR technique. For this reason, LANA immunohistochemistry is preferable to HHV-8 PCR for the evaluation of problematic vascular proliferations in HIV-positive individuals.
Calciphylaxis is an uncommon and often devastating syndrome of calcification of small vessels, leading to tissue infarction. The mechanism of how calcium deposits on small vessels is unknown. Recently, metalloproteinase digestion of elastin has been shown to enhance deposition of calcium, suggesting a possible mechanism of calciphylaxis. We describe a case of a patient who developed calciphylaxis after rapid weight loss, but had normocalcemia and normal renal function. She was found to have high levels of matrix metalloproteinases, which may have chemically altered elastin, allowing deposition of calcium on small vessels. Inhibitors of matrix metalloproteinases may be useful in the prevention and treatment of calciphylaxis.
BackgroundThe recent addition of immunotherapy as a treatment modality to surgery and radiation has vastly improved disease control for patients with keratinocyte-derived carcinomas (KCs) that are incurable with local therapies alone. With the advent of immune checkpoint inhibitors (ICPis) in non-melanoma skin cancers comes diagnostic and therapeutic challenges when considering treatment strategies for patients presenting with clinical perineural invasion (cPNI) of locally advanced KC of the head and neck.ObjectivesWe report four cases that convey the diagnostic and therapeutic complexity of managing patients with neuropathic symptoms from cutaneous neurotropic carcinomas of the head and neck. We also discuss an updated review regarding immunotherapies and perineural invasion within KC management.ConclusionPatients presenting with symptoms suspicious for cPNI warrant an expanded diagnostic evaluation to correlate neurological findings with neurotropic spread of disease. While nerve biopsies can be precarious in sensitive areas, a history of skin cancer and clinical presentation suggestive of neurotropism may be enough to pursue timely management in the form of surgery, radiation, and/or systemic therapy given each patient’s individual priorities, comorbidities, and prognosis. When adding ICPi as a treatment modality for patients with disease not amenable to local therapies, the potential for immune-related adverse events must be considered. A multi-disciplinary review and approach to the management of patients with KC and cPNI is essential for obtaining optimal patient outcomes.
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