Papillary carcinoma in thyroglossal duct cyst: Diagnosis by fine-needle aspiration cytology and immunocytochemistry.

Carcinoma associated with thyroglossal duct cyst (TDC) is extremely rare and when it occurs it is invariably papillary carcinoma. A 36-year-old man presented with a midline swelling in the upper part of neck, which was a cystic lesion with multiple septae in ultrasonogram, indicating a thyroglossal duct cyst. The CT scan findings also corroborated the ultrasound report. Fine needle aspiration (FNA) smears showed hemosiderin laden cyst macrophages and occasional papillary cluster of neoplastic cells with central psammoma body and rare intranuclear cytoplasmic inclusions. The neoplastic cells revealed positive reaction for thyroglobulin, galectin3, and CD44. FNA cytodiagnosis was thyroglossal duct cyst with cytologic features suggestive of papillary carcinoma. The histopathological diagnosis of the resected lesion, however, was metastatic papillary thyroid carcinoma in lymph node with cystic changes; there was positive reaction for thyroglobulin, galectin3, HBME1, and CK. Following this histopathology report, thyroidectomy was performed, which revealed lymphocytic thyroiditis and no evidence of papillary carcinoma. Review of paraffin sections of upper midline neck mass showed a cavity bound by thick fibrocollageneous wall and lined partly by epithelium consistent with papillary carcinoma. The cyst wall showed dense lymphomononuclear cell infiltration and germinal center formation. There were foci of papillary carcinoma in the cyst wall with frequent nuclear grooves, cerebriform nuclei and intranuclear cytoplasmic inclusions. The reviewed histopathological diagnosis was consistent with papillary carcinoma in thyroglossal duct cyst. Thus, the FNA cytodiagnosis of a rare case of papillary carcinoma in thyroglossal duct cyst, led to review and change in histopathological diagnosis achieving cyto-histopathological correlation.

Raf kinase inhibitor protein RKIP enhances signaling by glycogen synthase kinase-3ß.

Raf kinase inhibitory protein (RKIP) is a physiologic inhibitor of c-RAF kinase and nuclear factor κB signaling that represses tumor invasion and metastasis. Glycogen synthase kinase-3ß (GSK3ß) suppresses tumor progression by downregulating multiple oncogenic pathways including Wnt signaling and cyclin D1 activation. Here, we show that RKIP binds GSK3 proteins and maintains GSK3ß protein levels and its active form. Depletion of RKIP augments oxidative stress-mediated activation of the p38 mitogen activated protein kinase, which, in turn, inactivates GSK3ß by phosphorylating it at the inhibitory T390 residue. This pathway de-represses GSK3ß inhibition of oncogenic substrates causing stabilization of cyclin D, which induces cell-cycle progression and ß-catenin, SNAIL, and SLUG, which promote epithelial to mesenchymal transition. RKIP levels in human colorectal cancer positively correlate with GSK3ß expression. These findings reveal the RKIP/GSK3 axis as both a potential therapeutic target and a prognosis-based predictor of cancer progression.

Tubulolobular carcinoma of the breast with grooved and cerebriform nuclei: failure to identify this specific subtype in a case during routine fine needle aspiration cytology and histopathological diagnosis.

Tubulolobular carcinoma (TLC) is a rare tumor of the breast in which histologic features of both tubular and lobular carcinoma are combined. We report a case of TLC, in which the specific subtype was missed at routine cytologic and histopathological examination. A 69-year-old woman presented with a right breast lump. Imaging studies indicated a malignant lesion in right upper quadrant. Routine fine needle aspiration (FNA) cytology diagnosis was a duct cell carcinoma (small cell type). In a setting of cystic thyroid lesions, presence of excessive nuclear grooves, and rare intranuclear cytoplasmic inclusion, metastatic papillary thyroid carcinoma was also considered. However, both these possibilities were not supported by immunocytochemical findings (estrogen receptor+, thyroglobulin-, and chromogranin-). The histopathology diagnosis was invasive duct cell carcinoma. Review of FNA smears and paraffin sections led to the diagnosis of TLC, which was supported by positive immunohistochemical stainings for markers like e-cadherin and ß-catein.

Expression of estrogen receptor alpha and estrogen receptor beta in fine needle aspirates of breast carcinoma.

OBJECTIVE: To evaluate the expression of estrogen receptor beta (ERbeta) in fine needle aspirates (FNAs) and correlate the findings with its expression in tissue sections. STUDY DESIGN: In 38 cases of breast carcinoma, expression of estrogen receptor alpha (ERalpha) and ERbeta in aspirates and tissue sections was correlated with the cytologic and histologic grade of the tumor. RESULTS: ERalpha and ERbeta were expressed as nuclear staining in 80% and 90% of the cases in tissue sections and 47% and 45% of the cases in aspirates, respectively. Tissue expression of ERalpha (grade 1, 81%; grade 2, 100%) and ERbeta (grade 1, 94%; grade 2, 100%) was greater than in grade 3 tumors (ERalpha, 50%; ERbeta, 70%). In FNAs they were equally distributed in the different cytologic grades. In aspirates 30% of ERalpha negative tumors were positive for ERbeta, while in tissues 75% of ERalpha-negative tumors were positive for ERbeta (p = 0.007). CONCLUSION: Demonstration of ERbeta on FNA smears is feasible. It helps identify the specific subcohort of ERbeta-positive tumors in ERalpha-negative breast cancers; that may have therapeutic importance.

Raf kinase inhibitor protein expression in a survival analysis of colorectal cancer patients.

PURPOSE: Raf kinase inhibitor protein (RKIP) inhibits the Raf and nuclear factor kappa B signaling pathways, and suppresses metastasis in animal models. We examined whether RKIP expression in primary colorectal cancers (CRCs) correlates with the risk of metastasis and overall survival. PATIENTS AND METHODS: RKIP expression was examined immunohistochemically in three separate cohorts: a tissue microarray containing 276 samples from human tumors and normal tissues, and retrospective studies of 268 CRC patients and 65 early-stage CRCs. Overall and metastasis-free survival rates were measured. RESULTS: RKIP was expressed in normal epithelia but was reduced in metastatic tumors. RKIP expression in primary CRC was an independent prognostic marker for survival using multivariate Cox regression analysis (hazard ratio, 2.808; 95% CI, 1.58 to 4.96; P = .0002), independent of Dukes' stage. Patients with Dukes' C RKIP-positive tumors had similar 5-year survival rates as early-stage patients if tumors had equivalent RKIP expression levels. An independent study of early-stage CRCs confirmed that reduced RKIP expression predicted metastatic recurrence and reduced disease-free survival (hazard ratio, 4.5; 95% CI, 1.7 to 12.3; P = .003). RKIP expression was independent of sex, age, mitotic index, lymphatic and vascular invasion, depth of invasion, and tumor site, but correlated positively with apoptotic index (P = .024). Weak or loss of RKIP expression was the most significant and independent prognostic marker using a multivariate regression equation (hazard ratio, 4.5; 95% CI, 1.7 to 12.3; P = .003). CONCLUSION: RKIP expression in primary CRCs correlates with overall and disease-free survival, and can be useful for identifying early-stage CRC patients at risk of relapse.

Genetic profiling of stage I and II colorectal cancer may predict metastatic relapse.

A substantial number of patients with early-stage colorectal cancer relapse from metastatic disease. Identification of these patients by genetic profiling of their primary tumours may allow more informed follow-up and tailored administration of adjuvant therapy. Primary tumours from 70 patients with early-stage and largely microsatellite-stable colorectal cancer were profiled using metaphase-based comparative genomic hybridization (CGH) and the aberrations confirmed independently in a subset of patients using microarray-based CGH. Of the 70 cancers, 61 were amenable to CGH, and follow-up data was available from 56 patients. Genomic aberrations were correlated with patients' survival using univariate, multivariate and Kaplan-Meier survival curves. Metastatic primary tumours exhibited more complex genomic aberrations than non-metastatic primary tumours. Loss of chromosome 4p was an independent prognostic factor in early-stage colorectal cancer using multivariate analysis (Hazard ratio, 9.6; 95% CI, 3.3-28; P = 0.0001). Loss of both chromosome arms 8p and 18q had a statistically significant negative effect on disease-free survival. Moreover, primary tumours with loss of both chromosomes 4 and 14q bestowed poorer prognosis than tumours with loss of any one of the two chromosomes (P<0.0001). Genetic profiling of primary tumours of patients with early-stage colorectal cancer is of significant value in identifying the subset of patients who may relapse with metastatic disease. Accordingly, the molecular genetic features of primary tumours should be considered in the mainstream management of patients with this specific stage of the disease.