Annarita Palomba

Lymph node recovery from colorectal tumor specimens: recommendation for a minimum number of lymph nodes to be examined.

Lymph node involvement is the mostimportant prognostic factor for patients who have undergone radicalsurgery for colorectal carcinoma. An accurate examination of thesurgical specimens is mandatory for the correct assessment of the lymphnode status of the tumor. The risk of understaging is particularly highfor patients with tumors classified as Dukes B (TNM stage II). The aimof this study was to determine if a specified minimum number of lymphnodes examined per surgical specimen could have any effect on theprognosis of patients who had undergone radical surgery for Dukes Bcolorectal cancer. Between 1988 and 1995 a total of 140 patientsunderwent radical resection of Dukes B colorectal cancer by the samesurgeon (C.C.). The relation between clinicopathologic variables andsurvival was estimated using the Kaplan-Meier method. The Coxproportional hazard regression model was used to identify the variablesthat can independently influence survival. A median of 12 lymph nodes(range 3–38) was examined per tumor specimen. The 5-year survival rateof Dukes B patients who had had eight or fewer lymph nodes examinedafter surgery was 54.9%, whereas the survival rate for those who hadhad nine or more lymph nodes examined was 79.9% (p < 0.001). Cox regression analysis identified the number of lymph nodes asthe only independent prognostic factor (p = 0.01).Seventy patients with one to four metastatic lymph nodes (Dukes Cpatients) who had been operated on during the same period were includedin the survival analysis for comparison. The 5-year survival rate ofthe Dukes B patients with eight or fewer lymph nodes examined wassimilar to that of the 70 Dukes C patients (54.9% and 51.8%,respectively). Examination of eight or fewer lymph nodes in Dukes Bcolorectal patients may be considered a high risk factor for missingpositive lymph nodes in the surgical specimens. Our results suggestthat harvesting and examining a minimum of nine lymph nodes persurgical specimen may be sufficient for reliable staging of lymphnode-negative tumors.

Primary signet-ring cell carcinoma of the colon and rectum

PURPOSE: Colorectal signet-ring cell carcinoma (SRCC) is uncommon; discordant data have been previously reported about clinicopathologic features. Thirty-four cases of primary colorectal SRCC were retrospectively reviewed to clarify controversies. METHODS: Primary colorectal SRCC was diagnosed when the following criteria were satisfied: 1) the tumor was primary; 2) histologic material was adequate; 3) signet-ring cell represented more than 50 percent of the cancer. RESULTS: We identified 34 cases (1.1 percent) of 2,995 consecutive large bowel cancers collected at the Institute of Anatomic Pathology of Florence between 1985 and 1993. Patients ranged in age from 31 to 89 (mean, 63.5; median, 65) years; 19 were male, and 15 were female (male:female=1.3∶1). Fifteen tumors were located in the proximal colon, 11 in the rectum, and 8 in the distal colon. The gross shape was infiltrative in 24 cases and exophytic in 10; only 6 cases (17.6 percent) showed features of linitis plastica. Most cancers (61.8 percent) were Stage C, 29.4 percent were Stage B, and distant metastases were present in only three cases (8.8 percent). No Stage A case was found. Prognosis was extremely poor, and overall five-year survival rate was 9.1 percent. Survival was influenced significantly by tumor stage (P<0.01). CONCLUSIONS: Comparison of our data with the literature showed many differences that could be related to different applied diagnostic criteria. We underlined the importance of histology as reproducible criterion for diagnosis of primary colorectal SRCC.

CDX-2, cytokeratin 7 and cytokeratin 20 immunohistochemical expression in the differential diagnosis of primary adenocarcinomas of the sinonasal tract

Because the histopathological features of some primary adenocarcinomas of the sinonasal tract may show considerable overlap, we assessed the diagnostic value of a panel of immunohistochemical markers in the distinction between these malignancies. Paraffin-embedded tumour tissue sections from a series of 39 primary adenocarcinomas of the sinonasal tract, including 25 cases of intestinal-type adenocarcinoma (ITAC), 10 cases of salivary gland-type carcinoma and 4 cases of tubulopapillary low-grade adenocarcinoma were immunostained for CDX-2, cytokeratin 7 and cytokeratin 20. Diffuse nuclear staining for CDX-2 was identified in 80% of ITACs, while all non-ITACs were negative. Staining for cytokeratin 20 was positive in 84% of ITACs, including all cases negative for CDX-2, but negative in all other adenocarcinomas. Cytokeratin 7 was consistently positive in 88% of ITACs and in 100% of non-ITACs. Normal sinonasal epithelia expressed cytokeratin 7, but not CDX-2 and cytokeratin 20. Staining for CDX-2 and cytokeratin 20 has potential use in separating ITACs from other primary malignant glandular neoplasms of the nasal cavities and paranasal sinuses.

Tumor angiogenesis in lymph node-negative rectal cancer: correlation with clinicopathological parameters and prognosis.

AbstractBackground: Intratumoral microvessel density (MVD) could be used as a prognostic factor in colorectal cancer. We retrospectively analyzed the value of microvessel count in predicting the clinical outcome of stage I and II (Dukes A and B) rectal cancer patients. Methods: Eighty-four patients who had undergone curative resection of lymph node-negative rectal cancer were included. Tumor type and differentiation, the depth of local invasion, venous invasion, the character of the invasive margin, and the degree of lymphocytic infiltration were evaluated for each tumor specimen. Immunohistochemical staining for the CD31 endothelial antigen was performed to highlight the microvessels. Results: The median value of MVD was 45 microvessels. Low MVD (microvessels ≤45) was observed in 41 patients (48.8%), and high MVD (>45) was found in 43 (51.2%). The presence of conspicuous lymphocytic infiltration was significantly associated with increased vessel density. With uni- and multivariate survival analysis MVD did not show any prognostic significance. The character of the invasive margin was the only parameter with independent prognostic value. Conclusions: MVD does not seem to provide any additional prognostic information when compared with standard histopathological parameters in lymph node-negative rectal cancer. It is likely that the strong association between MVD and the presence of conspicuous lymphocytic infiltration may interfere with its predictive value.

Sinonasal carcinomas: Recent advances in molecular and phenotypic characterization and their clinical implications

Sinonasal carcinomas are rare tumors with an aggressive clinical behaviour which frequently pose a number of problems regarding the interpretation of diagnostic findings and the treatment. In addition, in comparison with other malignancies of the head and neck region, an elevated fraction of sinonasal carcinomas can be attributed to occupational exposure. This review is focused on the recent advances in the molecular and phenotypic characterization of sinonasal carcinomas, and their possible implications for the interpretation of epidemiological data, as well as for the diagnosis and treatment of these rare malignancies. The increasing knowledge on their phenotypic and genotypic features is progressively leading to a refinement in diagnosis, especially for poorly differentiated and undifferentiated lesions, as well as to the identification of markers which can be potentially useful to identify the early phases of carcinogenesis, to detect subclinical disease, to predict the response to therapy, and finally, that may represent potential targets for alternative treatments.

Character of the invasive margin in colorectal cancer

PURPOSE: The clinical significance and prognostic value of the histopathologic parameters used in both the Dukes and Jass classifications were evaluated to select those with an independent effect on survival after radical surgery for colorectal cancer. METHODS: The depth of local spread (limited to the bowel wall or extended beyond it), the number of metastatic lymph nodes (none, 1–4, more than 4), the character of the invasive margin (pushing or infiltrating), and the presence or absence of conspicuous peritumoral lymphocytic infiltration were assessed in 235 patients who had undergone radical resection for colorectal cancer. The influence of these variables on survival was studied by univariate and multivariate analysis. RESULTS: No significant difference in survival was found between patients with conspicuous peritumoral infiltrate and those without it; moreover, multivariate analysis failed to show any independent prognostic value for either lymphocytic infiltration or depth of local invasion. However, the character of the invasive margin and the number of metastatic lymph nodes were identified as the only variables with any independent importance on survival. Based on these data, a new prognostic model may be proposed; it uses the character of the infiltrative margin as a discriminating factor among patients within the lymph node-negative (Dukes A and B stages) and lymph node-positive (Dukes C1 and C2 subsets) groups. A good prognosis for Dukes A, B, and C1 patients was associated with pushing tumors; C1 and C2 patients with infiltrating tumors had a poor prognosis. On the whole, the new prognostic model has allowed for the placement of 59.6 percent of our patients into groups that provide a confident prognosis. The clinical outcome of Dukes A and B patients with infiltrating tumors is still uncertain. CONCLUSIONS: The character of the invasive margin is an important prognostic factor in colorectal cancer. The association of this parameter with the traditional Dukes classification may provide additional useful prognostic information and aid in the selection of those patients who could most benefit from adjuvant therapy.

Diagnostic Utility of Plag1 Immunohistochemical Determination in Salivary Gland Tumors

PLAG1 (pleomorphic adenoma gene 1) is a proto-oncogene whose overexpression is a crucial oncogenic event in salivary gland pleomorphic adenomas (PA), and in carcinoma ex-PA. The aim of the present study is to evaluate the sensitivity and the specificity of PLAG1 as a marker in the differential diagnosis of salivary gland benign and malignant tumors. We examined 101 cases, including 36 PAs, 8 myoepitheliomas, 3 basal cell adenomas, and 1 canalicular adenoma among benign tumors; 16 mucoepidermoid carcinomas, 10 adenoid cystic carcinomas, 8 acinic cell carcinomas, 8 polymorphous low-grade adenocarcinomas, 7 salivary duct carcinoma, and 4 epithelial-myoepithelial carcinoma among malignant tumors. PLAG1 was diffusely positive in 94.4% of PAs and in all myoepitheliomas, although with a lower staining intensity. Among malignant tumors, 2 (25%) polymorphous low-grade adenocarcinomas and 1 salivary duct carcinoma ex-PA were positive. In conclusion, PLAG1 is a marker with good specificity for PA and could be a useful diagnostic adjunct in the diagnosis of salivary gland tumors. In particular, this marker is negative in the most common salivary carcinomas, including adenoid cystic carcinoma, mucoepidermoid carcinoma, and acinic cell carcinoma. However, some mimickers of PA, like polymorphous low-grade adenocarcinoma, may show occasional positivity for PLAG1, thus limiting its diagnostic use. In addition, carcinoma ex-PA shows consistent positivity, and therefore should be considered as a diagnostic possibility in case of a malignant tumor with PLAG1 expression.

Current diagnostic strategies for undifferentiated tumours of the nasal cavities and paranasal sinuses

Franchi A, Palomba A & Cardesa A 
(2011) Histopathology 59, 1034–1045
Current diagnostic strategies for undifferentiated tumours of the nasal cavities and paranasal sinuses

Primary Combined Neuroendocrine and Squamous Cell Carcinoma of the Maxillary Sinus: Report of a Case with Immunohistochemical and Molecular Characterization

Abstract Neuroendocrine neoplasms represent a rare subset of tumors in the sinonasal tract. Combined tumors, with an endocrine and a non-neuroendocrine component, are exceedingly rare, and mainly consist of a combination of neuroendocrine carcinoma with adenocarcinomas. We present the clinico-pathologic and immunohistochemical features of a neuroendocrine carcinoma combined with squamous cell carcinoma, arising in the maxillary sinus. In addition, we evaluated the clonal origin of the two components through analysis of TP53 gene status. Both components were positive for cytokeratins AE1/AE3, while the squamous cell carcinoma was positive for cytokeratin 5/6 and p63, and the neuroendocrine carcinoma showed immunoreactivity for neuron specific enolase, chromogranin, synaptophysin and CD56. In situ hybridization for human papilloma virus and Epstein–Barr virus were negative in both components. A missense mutation in TP53 exon 7 (c.734G>C) and strong nuclear immunostaining for p53 were detected only in the neuroendocrine carcinoma. This suggests that the tumor either derived from one precursor cell with squamous differentiation, which underwent TP53 mutation and acquisition of a neuroendocrine phenotype, or it derived from two separate clones, one with mutated TP53 and neuroendocrine differentiation, and the other with wild type TP53 and squamous differentiation (collision tumor).

Immunohistochemical investigation of tumorigenic pathways in sinonasal intestinal‐type adenocarcinoma. A tissue microarray analysis of 62 cases

Franchi A, Palomba A, Fondi C, Miligi L, Paglierani M, Pepi M & Santucci M
(2011) Histopathology59, 98–105