Interlaboratory concordance in HER2 testing: Results of a Serbian ring-study.

PURPOSE: The purpose of this study was to assess the immunohistochemistry and chromogenic in situ hybridization (CISH) inter-laboratory consensus between national pathology laboratories in Serbia. METHODS: This study was conducted between 2013 and 2016. In 2013, HER2 results were evaluated using two sets of four different breast cancer specimens in five laboratories. A total of 20 immunohistochemistry and 20 CISH cases were tested. In 2014, there were 6 testing rounds, and a total of 24 specimens were analyzed, whereas in 2015 and 2016, seven testing rounds were conducted, with four additional cases (i.e. a total of 28 specimens). In 2014, 2015 and 2016, all institutions performed immunohistochemical analysis only. RESULTS: We found discrepan¬cies in HER2 immunohistochemical (IHC) results in all four surveys. IHC testing resulted in diagnostic discordance between participating centers in two (2/17) cases in 2013, two (2/24) in 2014, four (4/27) cases in 2015 and three cases (3/27) in 2016. The overall agreement among the centers was 79%, 85.5%, 83.5% and 89.4%, respectively. For CISH analyses, the results for 16 (84.2%) of 19 samples were consistent for all participants. Three results were found to be discordant, indicating a misdiagnosis rate of 15.8%. In all the discrepant cases, interinstitutional discordances were related to technical and evaluation issues. CONCLUSIONS: Our study highlights the difficulty encountered during HER2 testing using immunohistochemistry and CISH. This also emphasizes the need for rigorous quality control procedures for specimen preparation and analysis.

Intraparenchimal Leiomyoma of the Breast.

The most common location of the leiomyoma is uterus, small bowel and the esophagus, however they can occur in any organ. Intraparenchimal leiomyomas of the breast are very rare and only 30 cases were reported in the literature. These histologically benign tumors, may mimic malignancies and therefore may present a diagnostic challenge. Here, we present two new cases. The first case was a 50-year-old woman presented with a 4 cm firm mass in her right breast with discrete localized skin thickening/retraction. The second case was a 35-year-old woman presented with a painless palpable lump in the lower outer quadrant of her right breast. Physical examination, mammography and ultrasound as well as surgical excision were performed in both cases. According to histologic examination and immunohistochemical analysis, a diagnosis of smooth muscle tumor of the breast was made. These tumors clinically and radiologically mimic other breast lesions.  Neither imaging studies nor palpation allow distinction between benign and malignant tumors.

Lymph nodes behind the axillary neurovascular bundle: case report and cadaveric study of frequency and distribution.

Axillary clearance was undertaken in a 58-year-old male with massive lymph node enlargement caused by melanoma from an unknown primary site. We discovered a group of metastatic lymph nodes behind the axillary neurovascular bundle. This group of nodes (retro-axillary lymph nodes) could represent an extension of the subscapular group, or the seventh group of axillary lymphoid nodes. They were successfully removed using an ad hoc surgical technique, and the subsequent findings are presented herein. To check the frequency of these lymph nodes in this area, we conducted a study on 15 cadavers (30 armpits). The technique of cadaveric sampling is described. Retro-axillary tissue was histologically processed to determine the number of lymph nodes present. It was found that lymph nodes were present in the defined area in 18 of the 30 (60 %) armpits explored. We recommend assessment of the retro-axillary space during surgery entailing massive axillary lymph node involvement.

Optimization of breast cancer excision by intraoperative ultrasound and marking needle - technique description and feasibility.

BACKGROUND: We present a surgical technique and the preliminary results of breast cancer excision after insertion of a specially constructed marking needle into the tumor, controlled by intraoperative ultrasound. Resection margins were projected in six directions by ultrasound measurements, determined in relation to the needle, and resection was done in accordance with those measurements. The main objective was to obtain resection margins similar (equal) to those projected by intraoperative ultrasound (10 mm). METHODS: Detailed description of the technique is given. Thirty-two female patients undergoing breast-conserving surgery, up to 30 mm in diameter, for palpable and non-palpable invasive breast cancer, were operated on using this technique. Its feasibility was tested by analyzing the success (rate) of needle placement in the tumor, the measurements executed, and the performance of the excision. RESULTS: All stages of the technique were successfully performed to completion on all 32 patients. The procedure of needle placement and ultrasound measurement of distances took 11 min on average (between 6 and 20 min). The average distance of the tumor margin from the resection margin was 12.9 mm (2 to 30 mm, 95% confidence interval [11.9, 14.06]). There was one patient with a positive resection margin (3%). CONCLUSIONS: The technique of excising palpable and non-palpable breast cancer by intraoperative ultrasound and an especially constructed marking needle is feasible and comfortable to perform. Preliminary results imply that resection volume can be rationalized, with the same or better oncological safety.

Composite carcinoma of the stomach associated with sarcoid-like granulomas.

Composite glandular/exocrine-endocrine carcinoma of the gastrointestinal tract is a special tumor type composed of common adenocarcinoma and the neuroendocrine component comprising at least one-third of the whole tumor area. These tumors are rare in the stomach and mostly published as case reports. We describe a further case of a 36-year-old man being unique in that it was associated with extensive formation of sarcoid-like granulomas. Tumor consisted of, predominantly poorly differentiated, intestinal-type adenocarcinoma and poorly differentiated neuroendocrine, small cell carcinoma. The adenocarcinomatous and neuroendocrine areas were separated, but closely juxtaposed with focal areas showing gradual transition from one to another. Perigastric lymph node metastases corresponded either to neuroendocrine or adenocarcinomatous component. On immunohistochemistry, the exocrine part was positive for cytokeratin 7, whereas superficial well-differentiated parts showed positivity with cytokeratin 20 as well. The neuroendocrine component was negative with those two types of cytokeratin. Both adenocarcinomatous and neuroendocrine tumor portions showed carcinoembryonic antigen (CEA) immunoexpression. Neuroendocrine markers (chromogranin A, synaptophysin and neuron-specific enolase) were diffusely positive in the neuroendocrine component, and found only in the scattered cells within the neoplastic glands of the adenocarcinoma. Entire gastric mucosa and all perigastric lymph nodes were extensively affected by noncaseating, sarcoid-like granulomas. The absence of any clinical manifestations combined with the negative results of chest radiograph and laboratory test for the serum angiotensin converting enzyme argued against the possibility of systemic sarcoidosis.

[Multifocal Abrikossoff's granular cell tumour of the oesophagus--case report].

INTRODUCTION: Granular cell tumours, relatively uncommon soft tissue tumours, have been a matter of debate among pathologists regarding histogenesis for a long time. Less common locations are in the aerodigestive tract including the oesophagus. CASE OUTLINE: We have recently treated a rare case, a 37-year-old male, who was admitted due to dysphagia and a painful swallow with occasional pharyngo-nasal regurgitation followed with a mild loss of weight. Standard clinical examination including X-ray chest, ECG and laboratory tests did not show pathological findings. Barium contrast oesophagography demonstrated multiple ovoid defects in the wall of the oesophagus. CT scan of the chest confirmed luminal narrowing owing to the tumour of the upper oesophagus. Upper endoscopy showed unusual multifocal nodular lesions alongside the oesophageal axis covered by smooth mucosa. A primary biopsy specimen taken from the largest nodules confirmed an unusual pathological finding of the granular cell tumour. Subtotal, transpleural oesophagectomy was performed and reconstruction was derived by long colon segment interposition through the posterior mediastinum. The postoperative course was uneventful. The operative specimen consisted of four ovoid tumours alongside the oesophagus (the greatest diameter 0.5-1.8, average 1.25). All verified tumours histologicaly consisted of a spindle-shaped or polygonal cells containing small and large eosinophilic granules and central nuclei. Most tumour cells showed strongly positive immunohistochemical staining for S-100 protein. These tumour cells were partially positive for p-53 and Ki-67. No lymph node metastases were detected histologically. CONCLUSION: Multifocal granular cell tumour of the oesophagus is an unusual finding with low incidence, and rarely caused symptoms. Pathological features and multiplicity of such tumours emphasized malignant predisposition requiring surgical resection of the oesophagus.