Carmelo Urso

Histologic spectrum of carcinomas with eccrine ductal differentiation (sweat-gland ductal carcinomas)

Seven cases of sweat-gland carcinomas showing eccrine ductal differentiation (ductal carcinomas) are presented. The tumors had a variable histological appearance, but were basically characterized by the following histological elements: (a) tubular structures, sometimes cystic or having a “tadpole” appearance; (b) solid islands of squamous, basaloid, or clear cells; (c) periodic acid-Schiff-positive endoluminal and/or intracellular material; and (d) infiltrating growth. Immunocytochemically, tumor cells were positive for keratin and negative for actin. Endoluminal material contained carcinoembryonic antigen in five of seven cases. Although it is not yet clear whether carcinomas exhibiting eccrine ductal differentiation may represent a specific histotype or a group encompassing several distinct clincopathological entities, the histological analysis of the cases suggested that the wide spectrum of their histological appearances may be due to variable grades of differentiation.

Immunohistochemistry is highly sensitive and specific for the detection of NRASQ61R mutation in melanoma.

Testing for NRAS is now integral part in the assessment of metastatic melanoma patients because there is evidence that NRAS-mutated patients may be sensitive to MEK inhibitors, and RAS mutation is a common mechanism of acquired resistance during treatment with BRAF inhibitors. This study evaluated the sensitivity and specificity of immunohistochemical analysis using an N-Ras (Q61R) antibody to detect the presence of the NRASQ61R mutation in melanoma patients. A total of 98 primary cutaneous melanomas that have undergone examination of NRAS mutation were retrieved from a multicentric database. Formalin-fixed and paraffin-embedded melanoma tissues were analyzed for BRAF and NRAS mutations by independent, blinded observers using both conventional DNA molecular techniques and immunohistochemistry with the novel anti-human N-Ras (Q61R) monoclonal antibody (clone SP174). The antibody showed a sensitivity of 100% (14/14) and a specificity of 100% (83/83) for detecting the presence of an NRASQ61R mutation. Of the NRAS-mutated cases, none of the non-Q61R cases stained positive with the antibody (0/7). There were three cases with discordant NRAS mutational results. Additional molecular analysis confirmed the immunohistochemically obtained NRAS result in all cases, suggesting that a multiple analytical approach can be required to reach the correct sample classification. The reported immunohistochemical method is an accurate, rapid, and cost-effective method for detecting NRASQ61R mutation in melanoma patients, and represents a valuable supplement to traditional mutation testing. If validated in further studies, genetic testing would only be required for immunohistochemistry-negative patients to detect non-Q61R mutations.

Atypical histologic features in melanocytic nevi.

The atypical histologic features considered to be specific to dysplastic (atypical) nevi have been reported to occur in nevi that are common nevi by all other clinical and histologic features. The distribution and mutual relations among such features in nevi need to be further studied. Six histologic features (dimension > 5 mm, lentiginous proliferation, disordered nested pattern, melanocytic dyskaryosis, dermal lymphocytic infiltrate, suprabasal melanocytes) were analyzed in 253 melanocytic nevi with different clinical appearances. Atypical histologic features, found in 72% of nevi, occurred singly or formed numerous and highly variable combinations. Nevi formed a complex histologic spectrum comprising lesions showing a progressively increasing incidence of atypical features rather than two classes (common and dysplastic nevi). To divide the investigated lesions in objectively defined groups, we used a scoring system. In each nevus, a numeric value of 1 was assigned when each of the studied parameters was present and a value of 0 was assigned when each of these parameters was absent; on the basis of the final scores, nevi were divided in six different classes (classes 0–5). Diagnostic categories such as dysplastic nevi and common nevi seem to be inappropriate, as they do not reflect the real histologic complexity of such lesions.

Spatial association of melanocytic naevus and melanoma

A series of 233 consecutive primary cutaneous melanomas was histologically and clinically studied. Histologically, 53 melanomas (22.7%) were associated with naevus cells. Such a high degree of association suggests that melanocytic naevus may be a precursor of a large number of melanomas. Analysing the cases according to Clarks levels and Breslows index, a decrease in the naevus-melanoma association was seen with tumour progression, suggesting that advanced tumours may overgrow pre-existing nevus cells, appearing as de novo melanomas. The comparison between histological and clinical data suggest some interpretations of the natural history of melanoma.

Prognostic significance of c-erbB-2 oncoprotein expression in intestinal-type adenocarcinoma of the sinonasal tract.

The c‐erbB‐2 gene codes for a putative transmembrane protein, similar in structure to the epidermal growth factor receptor. Amplification and/or overexpression of the gene has been recently described with a prognostic significance in a variety of human adenocarcinomas.

Intestinal-type adenocarcinoma of the sinonasal tract: a clinicopathologic study of 18 cases.

Background Intestinal-type adenocarcinoma (ITAC) of the nose and paranasal sinuses is a relatively rare tumor. It commonly affects subjects exposed to wood or leather dust. Methods The authors present the clinicopathologic findings of 18 cases of sinonasal ITACs and review the proposed histologic classifications. Results All patients, except one, were males; mean age was 60 years (range, 41-79); in 9 cases an occupational exposure to wood or leather dust was found. Common presenting symptoms were epistaxis, nasal obstruction and rhinorrhea. Histologically, tumors were divided into four groups: well-differentiated (G1) ITACs = 3 cases; moderately differentiated (G2) ITACs = 8 cases; poorly differentiated (G3) ITACs = 2 cases; mucinous (M) ITACs = 5 cases. Immunocytochemically, 16/17 cases were positive for carcinoembryonal antigen, 1/17 for somatostatin, and 0/16 cases for gastrin. Conclusions Sinonasal ITACs are aggressive tumors, often diagnosed in a relatively advanced stage. Owing the close similarity of the microscopic aspects, a histologic classification of ITACs analogous to that of colonic adenocarcinomas is proposed.

Effect of sensory denervation with capsaicin on liver fibrosis induced by common bile duct ligation in rat.

Hepatic fibrosis represents an important stage in the progression of chronic liver disease to cirrhosis. In the present paper we have investigated whether capsaicin-sensitive neuropeptide-containing sensory neurons may participate in the development of liver fibrosis. The expression of hepatic fibrosis induced by common bile duct obstruction has been studied both in capsaicin- and vehicle-treated rats. Common bile duct-induced liver fibrosis was less marked in capsaicin-treated rats than in vehicle-treated rats. Diffuse alterations of liver parenchyma structure with marked collagen deposition and nodular regeneration occurred 8 weeks after common bile duct ligation in vehicle-treated animals, while none of the capsaicin-treated rats exhibited the formation of complete connective septa altering the parenchyma architecture. Both vehicle- and capsaicin-treated rats showed an increasing number of desmin-positive cells in the perivenular zone, but the density of these cells was lower in treated animals than in untreated rats. The hydroxyproline content of the liver increased after common bile duct ligation in a time-dependent manner. Eight weeks after bile duct obstruction vehicle-treated rats showed a 7-fold increase of liver collagen content in comparison to normal animals. This enhancement was about 3.5-fold in capsaicin-treated rats. These findings raise the possibility that the peripheral release of neuropeptides stored in sensory nerves might participate in the development of liver fibrosis following common bile duct obstruction.

Histological analysis of intraepidermal proliferations of atypical melanocytes

Fifty cutaneous pigmented lesions characterized by an intraepidermal proliferation of atypical melanocytes were reviewed. Several histological parameters (position of melanocytes in the epidermis, nuclear melanocytic atypia, presence or absence of pagetoid melanocytes, nucleoli, and others) were evaluated. On the basis of the results, the investigated cases were classified into three groups. In group 1, pagetoid melanocytes were present, melanocytic atypia was severe and continuous, all epidermal layers were involved by melanocytic proliferation, and a pattern of epidermal infiltration was recognized. In group 2, pagetoid meianocytes were absent, melanocytic atypia was mild-moderate and discontinuous, the lower epidermis only was involved by melanocytic proliferation, and a pattern of epidermal pseudoinfiltration was recognized. Group 3 cases were in an intermediate area between the two major groups. The results showed that intraepidermal proliferations of atypical melanocytes lie on one line, in which groups 1 and 2 account for the extremes.

Non-sentinel lymph node involvement in a patient with an atypical Spitz tumor and a positive sentinel node. Report of a case and review of the literature

We report a 20‐year‐old male patient with an atypical Spitz tumor, located in the dorsal aspect of his left hand, and a positive sentinel axillary lymph node. After lymphadenectomy, 1 of 23 non‐sentinel lymph nodes excised was found to contain small multiple deposits of large spindle atypical melanocytes. Reviewing the pertinent literature, 5 of 29 patients with atypical Spitz tumors and positive sentinel nodes who had undergone lymphadenectomy have shown non‐sentinel node involvement (17.2%), a proportion similar to that reported in melanoma patients. The exact nature of atypical Spitz tumors and the interpretation of cell deposits detected in sentinel nodes are still debated; data regarding the non‐sentinel lymph node involvement in patients with atypical Spitz tumors may contribute to better understand the real biological potential of such tumors.

MUCINOUS CARCINOMA OF SWEAT GLANDS

Three cases of primary cutaneous mucinous carcinoma of sweat gland origin are presented. Patients were a 47-year-old man and 2 females aged 70 and 71 years. The clinical and pathologic features of the described tumors were similar to those reported in the literature, except for 2 of the involved sites (abdominal skin and vulva), not previously described.