Laryngotracheal presentation of anaplastic thyroid carcinoma with squamous differentiation: seven cases demonstrating an under-recognized diagnostic pitfall.

AIMS: To describe a series of anaplastic thyroid carcinomas that mimicked primary head and neck squamous cell carcinoma (HNSCC) by virtue of both morphology and clinical presentation. METHODS AND RESULTS: Seven cases were identified in a 15-year period where a biopsy of an airway lesion that appeared to be squamous cell carcinoma was, in fact, anaplastic thyroid carcinoma. The tumours had squamous and/or spindle cell morphology, with only the squamous component being apparent in the airway biopsy. Some tumours arose within metaplastic (n = 3) or atypical (n = 3) epithelium, supporting the diagnosis of a primary mucosal tumour. Positive PAX8 (n = 5) and TTF-1 (n = 4) staining was identified. CONCLUSIONS: An endotracheal presentation of anaplastic thyroid carcinoma with squamous morphology may be misdiagnosed as a primary head and neck squamous cell carcinoma. PAX8 and TTF-1 expression are helpful in making the distinction, but the problem lies in suspecting a thyroid carcinoma in what appears to be a straightforward diagnosis of HNSCC.

Medullary carcinoma of the pancreas in a man with hereditary nonpolyposis colorectal cancer due to a mutation of the MSH2 mismatch repair gene.

Pancreatic adenocarcinoma has been reported in kindreds with hereditary nonpolyposis colorectal cancer (HNPCC). Medullary carcinoma of the pancreas is a recently described rare variant of pancreatic adenocarcinoma. We describe a man with colorectal carcinoma who subsequently developed pancreatic medullary carcinoma. The tumor displayed microsatellite instability and loss of expression of the mismatch repair proteins MSH2 and MSH6. Mutational analysis of the mismatch repair genes MLH1 and MSH2 demonstrated a pathogenic nonsense mutation within the MSH2 gene, which is consistent with a diagnosis of HNPCC. This report adds support to an association between HNPCC and pancreatic adenocarcinoma displaying the medullary phenotype, suggesting that medullary features in a pancreatic carcinoma may point toward a genetic cancer predisposition. To our knowledge, this is the first reported case of medullary carcinoma of the pancreas in a patient with HNPCC due to a mutation of the MSH2 gene.

Drastic reduction of calsequestrin-like proteins and impaired calcium binding in dystrophic mdx muscle.

Although the reduction in dystrophin-associated glycoproteins is the primary pathophysiological consequence of the deficiency in dystrophin, little is known about the secondary abnormalities leading to x-linked muscular dystrophy. As abnormal Ca(2+) handling may be involved in myonecrosis, we investigated the fate of key Ca(2+) regulatory membrane proteins in dystrophic mdx skeletal muscle membranes. Whereas the expression of the ryanodine receptor, the dihydropyridine receptor, the Ca(2+)-ATPase, and calsequestrin was not affected, a drastic decline in calsequestrin-like proteins of 150-220 kDa was observed in dystrophic microsomes using one-dimensional immunoblotting, two-dimensional immunoblotting with isoelectric focusing, diagonal two-dimensional blotting technique, and immunoprecipitation. In analogy, overall Ca(2+) binding was reduced in the sarcoplasmic reticulum of dystrophic muscle. The reduction in Ca(2+) binding proteins might be directly involved in triggering impaired Ca(2+) sequestration within the lumen of the sarcoplasmic reticulum. Thus disturbed sarcolemmal Ca(2+) fluxes seem to influence overall Ca(2+) homeostasis, resulting in distinct changes in the expression profile of a subset of Ca(2+) handling proteins, which might be an important factor in the progressive functional decline of dystrophic muscle fibers.

Maintaining Breast Cancer Specimen Integrity and Individual or Simultaneous Extraction of Quality DNA, RNA, and Proteins from Allprotect-Stabilized and Nonstabilized Tissue Samples.

The Saint James's Hospital Biobank was established in 2008, to develop a high-quality breast tissue BioResource, as a part of the breast cancer clinical care pathway. The aims of this work were: (1) to ascertain the quality of RNA, DNA, and protein in biobanked carcinomas and normal breast tissues, (2) to assess the efficacy of AllPrep(®) (Qiagen) in isolating RNA, DNA, and protein simultaneously, (3) to compare AllPrep with RNEasy(®) and QIAamp(®) (both Qiagen), and (4) to examine the effectiveness of Allprotect(®) (Qiagen), a new tissue stabilization medium in preserving DNA, RNA, and proteins. One hundred eleven frozen samples of carcinoma and normal breast tissue were analyzed. Tumor and normal tissue morphology were confirmed by frozen sections. Tissue type, tissue treatment (Allprotect vs. no Allprotect), extraction kit, and nucleic acid quantification were analyzed by utilizing a 4 factorial design (SPSS PASW 18 Statistics Software(®)). QIAamp (DNA isolation), AllPrep (DNA, RNA, and Protein isolation), and RNeasy (RNA isolation) kits were assessed and compared. Mean DNA yield and A(260/280) values using QIAamp were 33.2 ng/µL and 1.86, respectively, and using AllPrep were 23.2 ng/µL and 1.94. Mean RNA yield and RNA Integrity Number (RIN) values with RNeasy were 73.4 ng/µL and 8.16, respectively, and with AllPrep were 74.8 ng/µL and 7.92. Allprotect-treated tissues produced higher RIN values of borderline significance (P=0.055). No discernible loss of RNA stability was detected after 6 h incubation of stabilized or nonstabilized tissues at room temperature or 4°C or in 9 freeze-thaw cycles. Allprotect requires further detailed evaluation, but we consider AllPrep to be an excellent option for the simultaneous extraction of RNA, DNA, and protein from tumor and normal breast tissues. The essential presampling procedures that maintain the diagnostic integrity of pathology specimens do not appear to compromise the quality of molecular isolates.

Giant inflammatory polyposis coli as a manifestation of Crohn's disease in patients with coexistent cystic fibrosis.

Crohn's disease (CD) arising in children with cystic fibrosis (CF) is well recognized. Indeed, reports suggest that CD is significantly more common in patients with CF than in the general population. Giant inflammatory polyposis is a rare manifestation of idiopathic inflammatory bowel disease and may complicate both ulcerative colitis and CD. Giant inflammatory polyposis has not been specifically reported in patients with coexistent CF and CD. Herein, we report the occurrence of giant inflammatory polyposis in 2 boys attending a tertiary care hospital, with an established diagnosis of CF who subsequently developed CD. Both boys required surgical treatment for CD. In addition to classical features of CD, both colonic resection specimens showed giant inflammatory polyposis. The appearances were modified by the presence of a layer of thick mucus. It is suggested that the coexistence of CF in patients with CD may predispose to the development of giant inflammatory polyposis. In addition to contributing to their development, it also appears that there is a propensity for CF to alter the morphological appearance of giant inflammatory polyposis. This may lead to diagnostic confusion when examining endoscopic biopsies.