Metastatic Basal Cell Carcinoma of the Skin: A Comprehensive Literature Review, Including Advances in Molecular Therapeutics.

Basal cell carcinoma (BCC) of the skin is the most common type of malignant human tumor. In Europe, the incidence of BCC ranges from 44.6 to 128 cases per 100,000 inhabitants annually, whereas in the United States, the yearly incidence rate ranges between 500 and 1500. The global incidence has been calculated to be as high as 10 million cases of BCC per year. There are 2 main clinical patterns of BCC-the familial BCC in basal cell nevus syndrome and sporadic BCC. The etiology of cutaneous BCC is usually the result of the interaction between solar ultraviolet radiation and genetic factors. Somatic or germline mutations in the effector components of the hedgehog signaling pathway (ie, PTCH1, PTCH2, SMO or SUFU genes) are responsible for ∼90% of the cases of both sporadic and familial BCC, all causing a constitutive activation of the hedgehog pathway. Cutaneous BCC very rarely metastasizes, and diagnosis in metastatic sites can be very difficult. Metastatic BCC has weakly effective therapeutic options with a poor prognosis until few years ago. In 2012, small-molecule therapies, involving inactivation of the hedgehog signaling pathway, and capable of reducing tumor growth and progression have been introduced into clinical practice for advanced (locally advanced or metastatic) BCC. We performed a comprehensive literature review on metastatic BCC and found at least 915 cases reported to date. In addition, we extensively discussed the differential diagnosis of metastatic BCC, and outlined the advances in clinical therapeutics involving these small molecules.

Metastatic Cutaneous Basal Cell Carcinoma: Report of 2 Cases Preceding the Hedgehog Pathway Antagonists Era.

Basal cell carcinoma (BCC) of the skin is the most common type of malignant human tumor. However, metastatic BCC is a very rare event with weakly effective therapeutic options and a poor prognosis, until a few years ago. In 2012, small-molecule therapies, capable of inactivating the hedgehog signaling pathway and thus reducing tumor growth and progression, were introduced into clinical practice for the treatment of patients with advanced BCC. We present retrospectively 2 personal cases of metastatic BCC of the skin, from the premolecular therapy era, from primary tumors that arose years before in the head and neck area. The former case occurred in a 45-year-old woman with a history of recurrent BCC of the retroauricular skin who eventually died due to diffuse metastatic spread. The latter case concerned a 70-year-old man also with a history of recurrent BCC of the nasal-perinasal skin who developed multiple subcutaneous and lymph node metastases in the neck. In both cases, the diagnoses were based on biopsies of the metastatic sites. The first patient died 5 months after the diagnosis of metastatic disease, while the second was alive and disease-free 2 years after neck lymph node dissection and external radiation therapy, and then lost to follow-up. We extensively discuss several tumor entities with basal or basaloid features that may enter the differential diagnosis with BCC in metastatic sites. In addition, we briefly summarize the advances in clinical therapeutics using small molecules, which are now an integral part of the treatment of such advanced BCC cases.

Anaplastic Kaposi's Sarcoma of the Adrenal in an HIV-negative Patient With Literature Review.

Kaposi's sarcoma (KS) is a peculiar tumor of viral etiology, with the HHV8 rhadinovirus playing a fundamental role in its development. Several epidemiological categories of KS have been identified, of which the sporadic, endemic, iatrogenic, and the epidemic are the main ones. Several histologic disease morphologies have been described, such as inflammatory, angiomatous, spindle cell, mixed, and the anaplastic (sarcomatous) subtypes. The skin of the limbs is most commonly affected, but any other organ or site may be involved. Microscopically KS may enter the differential diagnosis with several different entities, and for this purpose the immunohistochemical detection of the viral latent nuclear antigen-1 (LNA-1) may be crucial. Sporadic KS is usually benign, but rarely it may be aggressive. Anaplastic histology heralds an ominous course in any clinical context. We report a case of anaplastic retroperitoneal KS, occurring in an HIV-negative adult man. This patient presented with a huge left suprarenal mass, which was totally resected, and initially diagnosed as inflammatory leiomyosarcoma, because of the monomorphic spindle cell tumor morphology. After 12 years the tumor recurred locally as an unresectable mass, which was biopsied and examined. At the time of recurrence, the histologic slides of the primary tumor were reviewed, and the previous diagnosis was changed to that of atypical KS. Histologically the recurrent tumor showed both spindle cell and epithelioid appearances. Strongly diffuse HHV8/LAN-1 immunopositivity was documented in both tumors. The final diagnosis for the entire case was anaplastic KS. Then, the patient died in a few months.