Pembrolizumab-induced follicular eruption and response to isotretinoin

Background: Pembrolizumab is a monoclonal antibody targeting PD-1. Folliculitis secondary to pembrolizumab has rarely been reported in the treatment of malignant melanoma. Case: A 49-year-old with a history of mild lower limb folliculitis developed metastatic malignant melanoma, and immunotherapy with pembrolizumab was initiated. Following 19 doses of pembrolizumab, a folliculocentric pustular eruption developed on the lower legs. Biopsy was consistent with folliculitis. Treatment with topical corticosteroids, high-dose prednisolone, lymecycline, clarithromycin, trimethoprim and clindamycin was unsuccessful. Pembrolizumab was stopped after 22 cycles, but the folliculitis persisted. Oral isotretinoin was required for disease control. Discussion: Drug-induced follicular eruptions have rarely been described with anti PD-1 therapy. Isotretinoin may be required to achieve remission.

P2X7 promotes metastatic spreading and triggers release of miRNA-containing exosomes and microvesicles from melanoma cells

Tumor growth and metastatic spreading are heavily affected by the P2X7 receptor as well as microvesicles and exosomes release into the tumor microenvironment. P2X7 receptor stimulation is known to trigger vesicular release from immune and central nervous system cells. However, P2X7 role in microvesicles and exosomes delivery from tumor cells was never analyzed in depth. Here we show that P2X7 is overexpressed in patients affected by metastatic malignant melanoma and that its expression closely correlates with reduced overall survival. Antagonism of melanoma cell-expressed P2X7 receptor inhibited in vitro anchorage-independent growth and migration and in vivo dissemination and lung metastasis formation. P2X7 stimulation triggered the release of miRNA-containing microvesicles and exosomes from melanoma cells, profoundly altering the nature of their miRNA content, as well as their dimensions and quantity. Among the more than 200 miRNAs that we found up-or-down-modulated for each vesicular fraction tested, we identified three miRNAs, miR-495-3p, miR-376c-3p, and miR-6730-3p, that were enriched in both the exosome and microvesicle fraction in a P2X7-dependent fashion. Interestingly, upon transfection, these miRNAs promoted melanoma cell growth or migration, and their vesicular release was minimized by P2X7 antagonism. Our data unveil an exosome/microvesicle and miRNA-dependent mechanism for the pro-metastatic activity of the P2X7 receptor and highlight this receptor as a suitable prognostic biomarker and therapeutic target in malignant melanoma.

Diffuse melanosis secondary to metastatic melanoma in a Nelore bull

We report a case of diffuse melanosis secondary to metastatic malignant melanoma in a Nelore bull. Clinical signs included isolation from the herd, epistaxis, hyperthermia, pale ocular membranes, mucoid diarrhea and dark urine. Despite anti-inflammatory and antibiotic therapy, the bull died 45 days after the onset of the clinical signs. The most striking lesion was diffuse black discoloration to the visceral organs including liver, spleen, lungs, lymph nodes, and kidneys; all these affect organs were moderately enlarged”. The urine was black. Histologically, 50-80% of the parenchyma of the liver, spleen and lymph nodes was obliterated by aggregates of melanin-loaded neoplastic melanocytes. Those neoplastic cells also occurred within capillaries of the liver, spleen, lymph nodes, urinary bladder, lungs and kidneys. Immunohistochemistry of neoplastic melanocytes was positive for Melan A and PNL2 markers. Abundant brown to black pigment was found in melanophages in the lungs, confirmed by IBA1 immunohistochemistry.

Suprasellar Melanocytoma with Leptomeningeal Seeding: An Aggressive Clinical Course for a Histologically Benign Tumor

Introduction. Meningeal melanocytoma (MM) is a very rare neuroectodermal neoplasm arising from the leptomeninges. Primary suprasellar melanocytomas are exceedingly rare, with only a handful of cases reported. The systemic spread of a nontransformed meningeal melanocytoma is an unusual occurrence. Herein, we report the first case of a primary sellar melanocytoma with cerebral and spinal meningeal seeding. Case Report. A 30-year-old male with no previous medical history presented to the endocrinology department with a loss of body hair. The endocrine workup concluded with isolated hypogonadotropic hypogonadism. The Magnetic Resonance Imaging (MRI) of the brain and sella revealed a large suprasellar mass continuous with the infundibulum of the pituitary gland. It was heterogeneously hyperintense on T1-, T2-, and FLAIR-weighted images and was enhanced with contrast, along with cerebral and spinal leptomeningeal spread. The patient was referred to the neurosurgery department, and a lumbar spine biopsy was indicated. The histopathological examination was suggestive of a grade I meningeal pigmented melanocytoma. Conclusion. Thus, primary sellar melanocytomas with leptomeningeal spread are an extremely rare phenomenon. Metastatic malignant melanoma should be ruled out. Being aware of differential diagnosis and the unusual behavior of meningeal melanocytoma will be necessary to manage the patient appropriately. Complete tumor resection is the best treatment whenever possible, and radiotherapy should be considered in case of unresectability or partial resection.

Aberrant Expression of Immunohistochemical Markers in Malignant Melanoma: A Review

Immunohistochemical stains are increasingly used to aid in the diagnosis of malignant melanoma, especially when the differentiation of the tumor is unclear based on examination with hematoxylin and eosin. However, aberrant expression of non-melanocytic markers has been reported in melanomas, which can sometimes be further complicated by the loss of conventional melanocytic markers. This review aims to summarize available data regarding unusual staining patterns in primary and metastatic malignant melanoma. It also raises awareness of the potential pitfalls and highlights the importance of appropriate use and interpretation of broad immunohistochemical markers in the context of clinical and histopathologic findings to facilitate the diagnosis of atypical cases of malignant melanoma.

Malignant melanoma without primary, presenting as solitary pulmonary nodule: a case report

Background Solitary pulmonary nodules are the most common incidental finding on chest imaging. Their management is very well defined by several guidelines, with risk calculators for lung cancer being the gold standard. Solitary intramuscular metastasis combined with a solitary pulmonary nodule from malignant melanoma without a primary site is rare. Case presentation A 57-year-old white male was referred to our lung cancer service with solitary pulmonary nodule. After positron-emission tomography, we performed an ultrasound-guided core needle biopsy of an intramuscular solitary lesion, not identified on computed tomography scan, and diagnosed metastatic malignant melanoma. The solitary pulmonary nodule was resected and also confirmed metastatic melanoma. There was no primary skin lesion. The patient received oral targeted therapy and is disease-free 5 years later. Conclusions Clinicians dealing with solitary pulmonary nodules must remain vigilant for other extrathoracic malignancies even in the absence of obvious past history. Lung metastasectomy may have a role in metastatic malignant melanoma with unknown primary.