Cutaneous squamous carcinoma in a patient with diabetic foot: an unusual evolution of a frequent complication.

After basal cell carcinoma, the cutaneous squamous cell carcinoma (cSCC) is the second most frequent non-melanoma skin cancer worldwide, and, classically, arises from the upper coats of the epidermis of sun-exposed areas or from skin areas constantly exposed to a chronic inflammatory stimulus. The occurrence of cSCC seems to be linked to several factors, including exposure to sunlight (or other ultraviolet radiations), immunosuppression, chronic scarring conditions and some familial cancer syndromes. Although the majority of cSCCs are adequately eradicated by surgical excision, a subgroup of cSCC may be linked with an increased risk of recurrence, metastasis and death. The incidence of type 2 diabetes mellitus is constantly increasing worldwide. Importantly, diabetes mellitus is a strong risk factor for cancers (including cutaneous tumors) and is highly related with poor cancer outcomes. At present, in the literature, squamous cell carcinoma developing in association with diabetic foot ulcers has been already reported in some reports; however, additional data are needed to make the clinicians aware of this rare, although possible, complication. Therefore, we herein report an unusual case of an elderly man with T2DM and a positive oncological history, presenting a cSCC involving the skin overlying the first toe of left foot. The growing cSCC appeared approximately 3 years after the appearance of a diabetic ulcer. LEARNING POINTS: Diabetic foot ulcers are an important and severe complication of diabetes mellitus and often can result in foot amputation.Chronic and non-healing diabetic foot ulcers are often observed in clinical practice.Clinicians should always take into consideration the malignant degeneration (e.g., cutaneous squamous cell carcinoma) of any chronic non-healing diabetic foot ulcer in elderly T2DM individuals.Timely surgical resection of a chronic, non-healing diabetic foot ulcer might preclude the development of a cutaneous squamous cell carcinoma.

NRASQ61K mutated diffuse leptomeningeal melanomatosis in an adult patient with a brief review of the so-called "forme fruste" of neurocutaneous melanosis.

Primary melanocytic tumors of central nervous system represent rare tumors arising from melanocytes of the leptomeninges. These neoplasms include focal forms like melanocytoma and primary malignant melanoma and diffuse forms like leptomeningeal melanocytosis and primary leptomeningeal melanomatosis. The clinical diagnosis remains challenging, with clinical and radiologic features overlapping with other more common diseases. Here we present a case of a 38 years old male with primary diffuse leptomeningeal melanomatosis with presence of a NRASQ61K mutation without features of neurocutaneous melanosis.

Association of CDK4 germline and BRAF somatic mutations in a patient with multiple primary melanomas and BRAF inhibitor resistance.

Many genetic alterations, including predisposing or somatic mutations, may contribute toward the development of melanoma. Although CDKN2A and CDK4 are high-penetrance genes for melanoma, MC1R is a low-penetrance gene that has been associated most consistently with the disease. Moreover, BRAF is the most frequently somatically altered oncogene and is a validated therapeutic target in melanoma. This paper reports a case of multiple primary melanoma with germline CDK4 mutation, MC1R variant, and somatic BRAF mutation in nine out of 10 melanomas, indicating that a common pathogenesis, because of a predisposing genetic background, may be shared among distinct subsequent melanomas of probable clonal origin. After 3 months of targeted therapy with BRAF inhibitor, our patient developed resistance with rapid progression of the disease leading to death. This is the first case in which early resistance to BRAF inhibitor has been reported in a patient with CDK4 germline mutation.

Lymphatic and blood vasculature in primary cutaneous melanomas of the scalp and neck.

BACKGROUND: Scalp/neck melanomas have a poor prognosis, possibly because of a rich vascular supply that prompts tumor cells' dissemination. METHODS: We compared the accuracy of immunohistochemical (IHC) staining with morphology for the identification of lymphovascular invasion in 156 scalp/neck melanomas. We then analyzed the association of vessel invasion and density with pathological features and survival. RESULTS: IHC-detected lymphatic vessel invasion (LVI) and blood vessel invasion (BVI) were identified in 34.6% and 13.5% of cases, respectively. IHC increased the LVI/BVI detection compared to morphology (40.4% vs 16.6%; p < .001). The degree of peritumoral and intratumoral blood vessel density (BVD) was greater than lymphatic vessel density (LVD). Ulceration was the only factor independently associated with intratumoral (p = .029) and peritumoral (p = .047) BVD. Tumor thickness was the only independent predictor of survival (p = .002). CONCLUSION: IHC allows accurate assessment of lymphovascular invasion in scalp/neck melanomas. In these tumors, we observed a high incidence of BVI, which deserves further investigations.

Bone metastases from primary cardiac sarcoma: case report.

Tumor spread from primary cardiac sarcoma to the bone is very rare and has a poor prognosis. Only six cases have been reported in the literature. We present a 32-year-old female patient with bone metastases from primary cardiac sarcoma.

M-CAM expression as marker of poor prognosis in epithelial ovarian cancer.

Currently available clinico-pathologic criteria provide an imperfect assessment of outcome for patients with advanced epithelial ovarian cancer (EOC). Identification of prognostic factors related to tumor biology might improve this assessment. We investigated the prognostic significance of the melanoma cell adhesion molecule (M-CAM) in EOC. Using the same antibody, M-CAM expression was tested by Western blotting in protein extracts and by immunohistochemestry in tissue microarrays generated from 133 consecutively resected, well characterized EOC samples. Fisher test, Kaplan-Meier method and Cox proportional hazards analysis were used to relate M-CAM expression to clinico-pathological variables and to time to progression (TTP) and overall survival (OS). In vitro biochemical analysis showed a progressively increased M-CAM expression from normal to malignant cells. M-CAM protein, detected immunohistochemically, was significantly associated with advanced tumor stage, serous and undifferentiated histotype, extent of residual disease and p53 accumulation. Presence or absence of M-CAM significantly divided patients according to their TTP (median, 22 vs. 79 months, respectively; log-rank p = 0.001) and OS (median, 42 vs. 131 months, respectively; log-rank p = 0.0003). In the subgroup of advanced stage patients who achieved complete response after front-line treatment, M-CAM expression and absence of residual disease were significantly associated with shorter TTP (p = 0.003, HR 5.25, 95% Cl 1.79-15.41 and p = 0.011, HR 3.77, 95% Cl 1.36-10.49 respectively) at the multivariate level. In the same sub-group of patients, M-CAM expression remained the only parameter significantly associated with OS (p = 0.005, HR 3.35, 95% Cl 1.42-6.88). M-CAM is a marker of early relapse and poorer outcome in EOC. In particular, M-CAM expression identifies a subgroup of front-line therapy-responding patients who undergo dramatic relapses, thus helping to better select patients who might benefit from new/alternative therapeutic modalities.