A Case of Amyloid Goitre in Heavy Chain Amyloidosis: Diagnostic Challenges and Clinical Implications.

Immunoglobulin heavy chain amyloidosis (AH amyloidosis) is an extremely rare subtype of immunoglobulin-derived amyloidosis and there is limited literature on how to diagnose and manage this disorder. We describe a rare case of AH amyloidosis with amyloid goitre and the importance of mass spectrometry in the identification of the different types of amyloids. While additional studies are needed, several observations suggest important practical implications, including differences in clinical picture, prognosis, and pathologic diagnosis. LEARNING POINTS: Immunoglobulin heavy chain amyloidosis is an extremely rare subtype of immunoglobulin-derived amyloidosis and amyloid goitre is even rarer.There is limited literature on how to diagnose and manage this disorder.This case portrays one of these cases - one of the few existing in the literature - and reinforces the diagnostic complexity of this entity.

A multinodular goiter as the initial presentation of a renal cell carcinoma harbouring a novel VHL mutation.

BACKGROUND: Secondary involvement of the thyroid gland is rare. Often the origin of the tumor is difficult to identify from the material obtained by fine-needle aspiration cytology. Renal cell carcinoma of the clear-cell type is one of the more common carcinomas to metastasize to the thyroid gland. Somatic mutations of the von Hippel-Lindau tumor suppressor gene are associated with the sporadic form of this tumor. We aimed to illustrate the potential utility of DNA based technologies to search for specific molecular markers in order to establish the anatomic site of origin. CASE PRESENTATION: A 54-yr-old Caucasian male complaining of a rapidly increasing neck tumor was diagnosed as having a clear-cell tumor by fine-needle aspiration cytology. A positive staining for cytokeratin as well as for vimentin and CD10 in the absence of staining for thyroglobulin, calcitonin and TTF1 suggested a renal origin confirmed by computed tomography. Using frozen RNA, obtained from cells left inside the needle used for fine needle aspiration cytology, it was possible to identify a somatic mutation (680 delA) in the VHL gene. CONCLUSION: In the presence of a clear-cell tumor of the thyroid gland, screening for somatic mutations in the VHL gene in material derived from thyroid aspirates might provide additional information to immunocytochemical studies and therefore plays a contributory role to establish the final diagnosis. Moreover, in a near future, this piece of information might be useful to define a targeted therapy.

Immunostaining and RT-PCR: different approaches to search for RET rearrangements in patients with papillary thyroid carcinoma.

Different techniques of molecular biology have been used to screen for RET rearrangements. More recently, immunohistochemistry has been used, assuming that RET is not expressed in normal thyroid follicular cells. The present study was designed to define the prevalence of RET expression in patients with papillary thyroid carcinoma, by immunohistochemistry and by RT-PCR; to search specifically for RET/PTC-1; -2; -3 rearrangements using RT-PCR, and to compare results obtained by immunohistochemistry with those obtained by RT-PCR. Immunohistochemistry was performed using a polyclonal antibody against tyrosine kinase domain of Ret protein. Screening for RET/PTC1-3 was performed using RT-PCR and specific primers for each rearrangement; complementarily, a subset of cases were tested using RET exon 10/11 primers designed to detect the expression of the wild-type RET. Positive staining was observed in 30 of 39 (77%) tumours. RET/PTC1-3 rearrangements were detected in 8 of 32 (25%) cases. Ten of 15 (67%) cases expressed the wild-type RET. Two tumours characterised by positive immunostaining, absence of RET 5' expression and absence of RET/PTC1-3 expression were considered as expressing a RET rearrangement different from RET/PTC-1, -2, or -3. In 3 of 10 tumours, expression of the wild-type RET coexisted with the expression of a RET rearrangement. Positive staining does not necessarily mean the presence of a rearrangement; it may correspond to the expression of the wild-type RET, RET rearrangement or both. On the contrary, positive staining without evidence for the expression of the extracellular domain of RET is highly suggestive of a RET rearrangement independently of the type. Refinement of diagnosis depends on RT-PCR with specific primers.

Flow cytometric S-phase fraction as a complementary biological parameter for the cytological grading of non-Hodgkin's lymphoma.

Fine-needle aspiration cytology (FNAC) is a technique that can overcome tissue-sampling disaggregation problems related to DNA flow cytometry analysis. The aim of this study, with long-term follow-up (median, 72 mo), was to investigate the prognostic value of DNA ploidy and S-phase fraction (SPF) in patients with non-Hodgkin's lymphoma (NHL), and additionally, the relevance of SPF in the grading of NHLs, using FNAC. The series comprised 76 patients with NHL (32 indolent and 44 aggressive tumors, including 14 Burkitt lymphomas) and 30 patients with reactive lymph node enlargement used as a control group. DNA flow cytometry was performed on fresh samples obtained by FNAC. NHL grading was done according to the updated Kiel classification. The 5-yr overall survival of patients with NHL was determined using the Kaplan-Meier method. All samples of the control group and 81.6% of the NHLs showed a DNA diploid pattern. Fourteen cases (18.4%) were DNA aneuploid with bimodal distribution: slight hyperdiploidy and near-tetraploidy. Despite the higher incidence of aneuploidy in aggressive than in indolent tumors (22.7% vs. 12.5%), no correlation between DNA ploidy and NHL grading was observed. In contrast, SPF revealed a strong correlation with grading (P=0.0001). The mean SPF values varied from 6.5% in indolent NHLs, to 20.4% in aggressive not-otherwise-specified (NOS) NHLs, and to 35.3% in Burkitt lymphomas. Nearly all aggressive NHLs had an SPF >15%, while the vast majority of indolent NHLs showed an SPF <10%. The mean SPF value in the reactive node group was 6.6%. NHL grading significantly was correlated to survival (P=0.004) only if the Burkitt lymphomas, which showed the best prognosis, were analyzed as an independent group. There was a trend that did not reach statistical significance (P=0.072) for a worse clinical outcome of patients with aneuploid tumors. When mean SPF values were used as cutoff points to divide both indolent NHLs and aggressive NOS NHLs into two proliferative subgroups, no differences in relation to survival were found (P=0.763 and P=0.994, respectively). Also, no proliferative difference was verified between indolent NHLs and the reactive lymph node group (P=0.223). These results show that flow cytometric SPF is a valuable complementary parameter for grading NHLs on FNAC samples, but it appears to give no additional prognostic information on subset analyses.

Preoperative diagnosis of suspicious parathyroid adenomas by RT-PCR using mRNA extracted from leftover cells in a needle used for ultrasonically guided fine needle aspiration cytology.

OBJECTIVE: To determine the usefulness of reverse transcriptase-polymerase chain reaction (RT-PCR) detection of parathormone (PTH) gene mRNA in needle aspirates to confirm the parathyroid nature of suspicious cervical lesions in patients with hyperparathyroidism. STUDY DESIGN: Ultrasound-guided fine needle aspiration cytology (FNAC) was performed on 12 patients with suspected parathyroid adenomas. The aspirates were subjected to cytologic and chromogranin A examination. Messenger RNA was isolated from left-over cells within the needle, and RT-PCR was used to amplify mRNA encoding PTH. RESULTS: The 12 aspirates were positive by PTH RT-PCR, and molecular diagnosis was confirmed by histologic examination. The lower sensitivity of cytologic and immunocytochemical methods was demonstrated, respectively, by 67% and 50% of positive results. Sensitivity assays demonstrated that with our system, PTH RT-PCR products are obtained from as few as 10 pg of parathyroid mRNA. CONCLUSION: The present study showed that RT-PCR-based analysis of PTH gene transcripts in aspirates, obtained by US-guided FNAC of cervical lesions suspicious for parathyroid adenoma, is a feasible, sensitive and specific method for preoperative diagnosis of parathyroid adenomas.

Duodenal subepithelial hyperechoic lesions of the third layer: Not always a lipoma.

Endoscopic ultrasonography is the most accurate procedure for the evaluation of subepithelial lesions. The finding of a homogeneous, hyperechoic, well-delimited lesion, originating from the third layer of the gastrointestinal tract (submucosa) suggests a benign tumor, generally lipoma. As other differential diagnoses have not been reported, echoendoscopists might not pursue a definitive pathological diagnosis or follow-up the patient. This case series aims to broaden the spectrum of differential diagnosis for duodenal hyperechoic third layer subepithelial lesions by providing four different and relevant pathologies with this echoendoscopic pattern.

Solid serous cystadenoma of the pancreas - Difficult assessment by EUS-FNA/FNB? / Cistoadenoma seroso sólido del páncreas: ¿valoración de dificultad mediante EUS-FNA/FNB?

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First case report of pancreatic myeloid sarcoma diagnosed through EUS-FNA / Primer caso clínico de sarcoma mieloide pancreático diagnosticado mediante AAF-EE

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Independent prognostic value of hormone receptor expression and S-phase fraction in advanced breast cancer.

OBJECTIVE: TO assess the prognostic value of immunocytochemically assessed hormone receptor expression and DNA flow cytometry data in advanced breast cancer. STUDY DESIGN: This prospective study with long-term follow-up evaluated the above parameters in relation to overall survival in 392 patients with advanced breast cancer (stages IIB, n = 106; IIIA, n = 66; IIIB, n = 174; and IV, n = 46) using fine needle aspiration cytology. RESULTS: Estrogen and progesterone receptor positivity was detected in 65.1% and 46.1% of the tumors, respectively. DNA aneuploidy was present in 70.9% of the cases, and the median S-phase fraction (SPF) was 9.4%. There was a significant correlation of aneuploidy and high SPF with lack of hormone receptors. The median SPF and SPF tertiles (cutoff values, 6.5% and 12%), applied in the whole series, showed a significant correlation with survival, whereas if SPF was used according to ploidy status, no prognostic significance was found. No differences in relation to survival among different DNA aneuploidy subclasses were verified. In univariate analysis, clinical staging, hormone receptors, DNA ploidy and SPF showed a statistically significant correlation with the overall survival. In multivariate analysis only DNA ploidy did not maintain independent prognostic significance. CONCLUSION: Hormone receptor expression and flow cytometric SPF are independent prognostic factors in advanced breast cancer.