Impact of second histopathological review of melanocytic skin lesions at a melanoma reference center in Brazil.

BACKGROUND: After the biopsy of a suspicious melanocytic lesion, patients depend on the pathologist's precision of specimen evaluation. METHODS: We assessed the agreement between histopathological reports made by general pathologists and reviewed by a dermatopathologist to evaluate the impact on the patient's management. RESULTS: In 79 cases analyzed, underdiagnosis was observed in 21.6% and overdiagnosis in 17.7%, resulting in changes in the patients' conduct. The assessment of the Clark level, ulceration and histological type showed mild agreement (P<0.001); the Breslow thickness, surgical margin, and staging showed moderate agreement (P<0.001). CONCLUSIONS: A dermatopathologist's review should be incorporated into the routine of reference services for pigmented lesions.

Histopathologic Diagnosis Discrepancies Between Preoperative Endoscopic Forceps Biopsies and Specimens Resected by Endoscopic Submucosal Dissection in Superficial Gastric Neoplasms.

BACKGROUND: The standard of practice when a superficial lesion was identified during upper GI endoscopy is to take an endoscopic forceps biopsy (EFB) of the lesion. The histopathologic findings then will determine the management plan. Endoscopic submucosal dissection (ESD) enables en-bloc resection for early neoplasms of the gastrointestinal tract and provides an adequate specimen that permits a more reliable histopathologic assessment. The objective of this study was to determine the rate of histopathologic discrepancy between EFB and specimens resected by ESD, and to identify the predisposing risk factors for this discordance. MATERIALS AND METHODS: This is a retrospective study, enrolling patients with superficial gastric neoplasms that underwent EFB followed by ESD. We divided cases to concordant or discordant group according to the histopathologic diagnosis of EFB and ESD specimens. We also analyzed the features that may have influenced the occurrence of histopathologic discordance and the association between discordant samples of adenocarcinoma and neoplastic invasion to deeper layers. RESULTS: A total of 115 gastric ESD procedures were performed with 84 patients meeting the inclusion criteria. Histopathologic discordance between EFB and ESD specimens were observed in 35.8% of cases (30/84 lesions). The univariant-bivariant analysis and multivariate logistic regression analysis showed that histologic discordance was closely related to the size of the lesions ( P =0.028). CONCLUSION: Histopathologic discrepancy between EFB and ESD specimens may occur in approximately one-third of cases, particularly for lesions over 20 mm, which may lead to crucial delays in gastric cancer precise diagnosis and treatment.

Molecular and immunohistochemical analyses of uveal melanoma patient cohort.

Uveal melanoma is a rare form of melanoma and the most frequent primary eye malignancy in adults. The major molecular alterations underlying uveal melanoma pathogenesis affect mainly the GNAQ, GNA11, SF3B1, and BAP1 genes. In this study, we somatically genotyped 31 Brazilian uveal melanomas for BRAF, GNA11, GNAQ, SF3B1, and BAP1 gene mutations and assessed BRCA2 and p53 protein expression. GNAQ and GNA11 mutations were detected in 60%, and SF3B1 mutation rate was 30%. p53 Immunostaining was markedly positive in 5/31, and 3/31 samples showed negative BRCA2 expression. This study supports the importance of these key genes in uveal melanoma tumorigenesis; p53 and BRCA pathways seem to play a role in a subset of patients, possibly heralding unfavorable prognosis.

Histopathological and immunohistochemical (cytokeratins AE1/AE3) study of the parametrium of patients with early stage cervical cancer.

OBJECTIVE: This study was undertaken in order to evaluate histopathological and immunohistochemical (cytokeratins AE1/AE3) characteristics of parametrial invasion in patients with early stage cervical cancer. STUDY DESIGN: Thirty patients with stage IB squamous cell carcinoma (SCC) of the cervix submitted to radical hysterectomy from November 2001 to September 2002 were prospectively studied. Histopathological studies were undertaken using tissue samples (n=60) taken from the parametrium, whose surgical margins were inked and the entire parametrial tissue was fixed in 10% buffered formalin and embedded in paraffin for further analysis using hematoxylin-eosin (H&E) staining. Specific patterns of parametrial involvement (continuous invasion, parametrial lymphatic vascular space invasion (LVSI) and/or parametrial lymph nodes' (PMLN) metastasis) were recorded. Parametrial samples, in which the histological examination showed no tumor involvement, were immunohistochemically assessed through monoclonal antibodies for cytokeratins AE1/AE3. Clinicopathological characteristics of the patients were also recorded. RESULTS: Patient's mean age was 49+/-10 years (27-73 years). Histopathological analysis (H&E) showed parametrium involvement in 12 patients (40%) of whom 11 (92%) presented parametrial LVSI, 9 (75%) continuous invasion and 4 (33%) PMLN metastasis. Micrometastasis was detected in 3/18 (17%) of the patients with histologically negative parametrium by H&E evaluation. Parametrial involvement detected by H&E was associated with tumor recurrence (p=0.009) and survival (p=0.025). This association was not correlated with the presence of parametrial micrometastasis (p=1.00 and 1.00, respectively). CONCLUSIONS: The process of parametrial spreading in patients with SCC of the cervix may develop several histopathological patterns, which are associated with clinicopathological features and prognosis. Our findings highlight the importance to ink the parametria, which is the only way to define the pattern of tumor spreading. The clinical significance of micrometastasis, detected in patients with histologically negative parametrium by H&E, remains to be clear.

Ossifying fibroma: a rare cause of orbital inflammation.

PURPOSE: To describe the clinical and radiologic features of 4 cases of ossifying fibroma affecting the orbit and to review the literature on orbital involvement by the tumor. METHODS: Small case series. RESULTS: Four patients (3 children and 1 adult) with ossifying fibromas invading the orbit were examined. Two of the 3 children were examined for ossifying fibromas on the orbital roof. One had the psammomatoid form of the disease and the other the trabecular variant. Despite striking differences in the histologic pattern and in the radiologic appearance of the lesions, both children displayed a significant degree of orbital inflammation mimicking orbital cellulitis. The third child and the adult patient had the orbit involved by trabecular ossifying fibromas invading the orbital floor. The tumor of the adult clearly originated in the maxilla, filled the maxillary sinus, and eroded the orbital floor. The tumor of the third child occupied the maxillary, ethmoid, and sphenoid sinuses. In both cases, the clinical presentation was painless eye dystopia and proptosis. CONCLUSIONS: Regardless of the histologic pattern (trabecular or psammomatoid), ossifying fibromas can induce a substantial degree of orbital inflammation in children and must be included in the differential diagnosis of acute orbital inflammation during childhood.

Clinicopathological features influencing pelvic lymph node metastasis and vaginal and parametrial involvement in patients with carcinoma of the cervix.

PURPOSE: This study was undertaken to evaluate clinical and pathologic findings that predicted pelvic lymph node metastasis and parametrial and vaginal involvement in patients with stage IB carcinoma of the cervix. METHODS: 71 patients with diagnosis of stage IB (FIGO) cervical cancer were prospectively studied from December 1997 to August 2002. The patient's age, clinical stage (IB1 or IB2), histological classification, grade of differentiation, tumor volume, and lymphatic vascular space invasion (LVSI) were evaluated. Statistical methods included chi2 test and Fisher's exact test to evaluate significant differences between the groups. The level of significance was set at p < 0.05. RESULTS: The clinical stage was IB1 in 51 patients (71.8%) and IB2 in 20 patients (28.2%). The histological classification identified squamous cell carcinoma in 60 patients (84.5%) and adenocarcinoma in 11 patients (15.5%). The average tumoral volume was 22.8 +/- 24.3 cm3 (0.3-140.0 cm3). The tumor was well differentiated (G1) in 8 (11.3%), moderately differentiated (G2) in 40 (56.3%) and poorly differentiated in 23 (32.4%) of the cases. The presence of LVSI was detected in 14 patients (19.7%) and was associated with pelvic lymph node metastasis and vaginal and parametrial involvement (p = 0.002, p = 0.001 and p < 0.001; respectively). The average number of positive pelvic lymph nodes was significantly higher in the patients with LVSI compared with patients without LVSI (2.47 +/- 2.8 vs. 0.33 +/- 0.74; p = 0.001). There was no association of age, clinical stage, histological classification, grade of differentiation or tumor volume with pelvic lymph node metastasis and vaginal and parametrial involvement. CONCLUSION: The presence of LVSI is significantly associated with pelvic lymph node metastasis and vaginal and parametrial involvement in patients with stage IB cervical carcinoma.

Expression of p53, Ki-67, and CD31 in the vaginal margins of radical hysterectomy in patients with stage IB carcinoma of the cervix.

OBJECTIVES: This study was undertaken to evaluate the expression of p53, Ki-67, and CD31 both in the tumor and in the vaginal margins of radical hysterectomy in patients with stage IB squamous cell carcinoma of the cervix, as an attempt to use these proteins as possible markers for residual tumor in cervical cancer. METHODS: Thirty patients with stage IB squamous cell carcinoma of the cervix were submitted to radical hysterectomy (study group), and thirty patients with uterine myoma were submitted to vaginal hysterectomy (control group) and were prospectively studied from November 2001 to September 2002. Tissue samples were taken from the tumor or cervix, anterior vaginal margin (AVM), and posterior vaginal margin (PVM) and were immunohistochemically evaluated by monoclonal antibodies for p53, Ki-67, and CD31. Vaginal samples in which the histological examination showed tumor involvement were excluded from the study. RESULTS: Patient's mean age was 48.7 +/- 10.4 years (27-73 years). The clinical stage was IB1 in 22 patients (73.3%) and IB2 in eight patients (26.7%). The expressions of p53, Ki-67, and CD31 were significantly higher in the tumor than in the benign cervix (P < 0.001). Higher expressions of these markers were noted in the vaginal margins of radical hysterectomy in patients with cervical carcinoma compared to the vaginal margins of control patients. This association was demonstrated for p53 in the AVM proximal (P = 0.045), for Ki-67 in AVM proximal (P < 0.001), AVM distal (P < 0.001), PVM proximal (P = 0.009), and PVM distal (P < 0.001), and for CD31 in AVM proximal (P = 0.003) and AVM distal (P = 0.018). There was no difference in p53, Ki-67, and CD31 expression between the proximal and distal regions of the vaginal margins in patients with carcinoma of the cervix. CONCLUSION: The expressions of p53, Ki-67, and CD31 were significantly higher in both the histologically positive (cervical tumor) and negative (vaginal margins) tissues of patients who had undergone radical hysterectomy for cervical cancer compared to the benign control tissues.