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.

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.

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.

Selected case from the Arkadi M. Rywlin International Pathology Slide Series: Asymmetric, segmental glomerulocystic kidney in an infant with tuberous sclerosis complex.

A Hispanic newborn male, the product of nonconsanguineous parents, exhibited major and minor signs of tuberous sclerosis complex (TSC). MRI of the abdomen disclosed a discrete unilateral, cystic, right upper pole renal mass that prompted a nephrectomy. Histologic examination showed a polycystic renal mass that involved all segments of the nephron, with a preponderantly glomerulocystic pattern. The cysts were rounded, uniform, and small, most measuring 2 to 3 mm in diameter. The lining of the cysts was hyperplastic, made up of tall epithelial cells with eosinophilic granular cytoplasm and large nuclei, and focally formed mounds and papillary tufts. DNA analysis detected a constitutional deletion of exon 1 in the TSC2 gene on chromosome 16p13.3. Cystogenesis in TSC2 is manifested because of alteration or dysfunction of the primary cilium, where polycystin, the gene product of PKD1 gene, is localized. Renal cysts are often seen in TSC, varying in number from a few to innumerable, involving all segments of the nephron, including Bowman spaces, and are currently considered as one of the minor diagnostic features. A glomerulocystic pattern is a rare form of kidney involvement in TSC that aptly describes the innumerable cystically dilated Bowman spaces. Glomerulocystic kidney associated with the aforementioned hyperplastic epithelial lining (TSC epithelium) is sufficiently characteristic that could conceivably serve as a major TSC feature in the future.

Selected case from the Arkadi M. Rywlin international pathology slide series: diffuse dendriform pulmonary ossification: report of 2 cases with review of the literature.

Two cases of diffuse dendriform pulmonary ossification (DPO) are presented, one of the secondary type and the other of the idiopathic type. Case 1 was an adult female patient who underwent thoracic surgery to remove a posterior mediastinal bronchogenic cyst, which was discovered on a computed tomography scan performed after an episode of pneumonia when traction bronchiectasis with interstitial lung disease/fibrosis was also suspected in the lungs. Histologic examination performed on the resected lung tissue revealed numerous scattered small osseous spicules on a background of intense interstitial inflammation and fibrosis, leading to further clinical and laboratory investigations and the final diagnosis of DPO secondary to lung involvement by scleroderma. Case 2 was an adult male patient who underwent thoracoscopic exploration after a computed tomography scan, which revealed traction bronchiectasis with linear thickening of the interstitial lung tissue. Histologic examination of the lung tissue specimen revealed numerous osseous spicules in the absence of interstitial septal inflammation. Noteworthy in this case were also some nodules of collagenized tissue similar to those seen in the lungs of patients affected by Ehlers-Danlos syndrome. The absence of any clinical sign or symptoms related to Ehlers-Danlos syndrome attest to the nonspecificity of these pulmonary fibrous nodules. No case of DPO secondary to scleroderma has been reported in the literature so far, although around half of the patients with scleroderma manifest pulmonary diseases. Idiopathic DPO is even rarer, usually discovered postmortem, with only 20 cases diagnosed in life with lung biopsies taken by open surgery or through a thoracoscopic approach. DPO is often misdiagnosed radiologically as bronchiectasis and/or interstitial lung disease/fibrosis.

Primary malignant melanoma of the esophagus: a clinicopathologic study of a case with comprehensive literature review.

Primary malignant melanoma originating in the digestive tract is particularly rare, mainly affecting the anorectum and oral cavity. Primary malignant melanoma of the esophagus has been the subject mostly of case reports. This tumor has a dismal prognosis with a frequency estimated to be approximately 0.1% to 0.2% of all esophageal malignancies. According to the review by Volpin et al of November 2002, 238 cases of primary malignant melanoma of the esophagus have been published up to early 2001. We present an additional case of primary malignant melanoma of the esophagus of the amelanotic variant in a 69-year-old man. The patient was preoperatively investigated by esophageal endoscopy and endoscopic ultrasound. The surgically resected tumor specimen was examined histologically and supplemented by immunohistochemical and ultrastructural analysis. Intra-abdominal relapse occurred after 8 months at the site of surgery, necessitating repeat resection. The patient died of advanced intra-abdominal disease 14 months after the primary diagnosis. A comprehensive computerized (PubMed/Medline) review of the world literature was also carried out and 99 additional cases (after the review by Volpin et al) were found, 9 of them from the 1990s which escaped previous tabulations, and 90 from the years 2000 to 2010, amounting to a grand total of 337 ever published.

Spontaneous cutaneous cholesterol crystal embolism with focal clinical symptomatology: report of a case in an unusual location with secondary histological changes reminiscent of atypical decubital fibroplasia.

Cholesterol crystal embolization (CCE) is one of the many complications of atherosclerosis. CCE is usually an iatrogenic event occurring either after vascular surgery, usually aortic surgery, or invasive angiographic investigations or in the course of anticoagulant or thrombolytic therapy. More rarely, it occurs after trauma or even in the absence of any inciting cause. CCE may manifest with single or multiorgan involvement. Skin involvement is usually seen in the context of a systemic disease, especially affecting the lower extremities and lower trunk. We report on a rare case of isolated spontaneous focal cutaneous involvement of the upper limb, with peculiar mesenchymal and reactive histological changes. A 65-year-old man with a clinical history of atherosclerosis was admitted complaining of a nonhealing painful skin ulceration on his left elbow for 5-month duration. A skin biopsy was taken, and histopathological examination documented an intrarteriolar cholesterol embolus in the dermis along with a peculiar adjacent bizarre fibroblastic reaction, of the type usually seen in atypical decubital fibroplasia of debilitated patients. The ulceration was surgically excised, and the wound was sutured and repaired. At 18-month follow-up, the patient has no evidence of local disease.