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1.
Am J Surg Pathol ; 44(2): 162-173, 2020 02.
Article in English | MEDLINE | ID: mdl-31567189

ABSTRACT

This study was undertaken to determine the frequency, and the clinicopathologic and genetic features, of colon cancers driven by neurotrophic receptor tyrosine kinase (NTRK) gene fusions. Of the 7008 tumors screened for NTRK expression using a pan-Trk antibody, 16 (0.23%) had Trk immunoreactivity. ArcherDx assay detected TPM3-NTRK1 (n=9), LMNA-NTRK1 (n=3), TPR-NTRK1 (n=2) and EML4-NTRK3 (n=1) fusion transcripts in 15 cases with sufficient RNA quality. Patients were predominantly women (median age: 63 y). The tumors involved the right (n=12) and left colon unequally and were either stage T3 (n=12) or T4. Local lymph node and distant metastases were seen at presentation in 6 and 1 patients, respectively. Lymphovascular invasion was present in all cases. Histologically, tumors showed moderate to poor (n=11) differentiation with a partly or entirely solid pattern (n=5) and mucinous component (n=10), including 1 case with sheets of signet ring cells. DNA mismatch repair-deficient phenotype was seen in 13 cases. Tumor-infiltrating CD4/CD8 lymphocytes were prominent in 9 cases. Programmed death-ligand 1 positive tumor-infiltrating immune cells and focal tumor cell positivity were seen in the majority of cases. CDX2 expression and loss of CK20 and MUC2 expression were frequent. CK7 was expressed in 5 cases. No mutations in BRAF, RAS, and PIK3CA were identified. However, other genes of the PI3K-AKT/MTOR pathway were mutated. In several cases, components of Wnt/ß-catenin (APC, AMER1, CTNNB1), p53, and TGFß (ACVR2A, TGFBR2) pathways were mutated. However, no SMAD4 mutations were found. Two tumors harbored FBXW7 tumor suppressor gene mutations. NTRK fusion tumors constitute a distinct but rare subgroup of colorectal carcinomas.


Subject(s)
Adenocarcinoma/diagnosis , Adenocarcinoma/genetics , Biomarkers, Tumor/genetics , Colonic Neoplasms/diagnosis , Colonic Neoplasms/genetics , Oncogene Proteins, Fusion/genetics , Receptor Protein-Tyrosine Kinases/genetics , Adenocarcinoma/pathology , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Colonic Neoplasms/pathology , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Male , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Middle Aged , Neoplasm Staging , Oncogene Fusion , Oncogene Proteins, Fusion/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Receptor, trkA/genetics , Receptor, trkA/metabolism , Receptor, trkB/genetics , Receptor, trkB/metabolism , Receptor, trkC/genetics , Receptor, trkC/metabolism
2.
World J Surg Oncol ; 17(1): 55, 2019 Mar 22.
Article in English | MEDLINE | ID: mdl-30902091

ABSTRACT

BACKGROUND: Mixed neuroendocrine-non-neuroendocrine tumors (MINEN) of the gallbladder are extremely rare; indeed, the English expert literature reports a mere handful of case reports and case series on this topic. According to the WHO classification of 2010, MINEN are considered to be tumors consisting of two major components, neuroendocrine and non-neuroendocrine, each of which hosts at least 30% of the total cellular population. To date, the etiology and pathogenesis of MINEN have not been precisely determined and the non-specific symptoms generally result in late diagnosis (mainly in the terminal stages of the condition) and contribute to the generally poor prognosis. As far as the management of the disease is concerned, radical surgery plays a crucial role; however, the significance of surgical debulking and biological therapy applying somatostatin analogues has not yet been determined. CASE PRESENTATION: A 56-year-old female was referred to our department for a rapidly progressing tumor in the subhepatic area along with the infiltration of S5 and S6 liver segments. With regard to preoperative findings, the tumor appeared as operable, although, during the surgery, an extensive involvement of the hepatoduodenal ligament by the tumor through the lymph nodes was revealed. Due to acute perioperative bleeding from the necrotic tumor, we decided to perform modified resection. Histologically, the tumor was confirmed as MINEN of gallbladder, where the neuroendocrine component was dominant over the non-neuroendocrine component. Six weeks after the discharge, the patient underwent a follow-up CT revealing large recurrence of the disease. Thereafter, the patient was started on systemic therapy with etoposide and carboplatin in combination with somatostatin analogues. Thirteen months after the surgery, the patient is in good clinical condition, and while a recently performed PET/MRI scan revealed a hepatic lesion and hilar lymphadenopathy in full regression, there was a spread of small peritoneal and pleural metastases. The patient remains in the follow-up care. CONCLUSIONS: The occurrence of mixed neuroendocrine-non-neuroendocrine neoplasms is extremely rare. Radical surgery remains the only potentially effective approach to the cure of this disease. The role of biological therapy and debulking in the management of the disease has not yet been precisely defined. In our experience, both of these methods have the potential to positively influence overall survival rates and the postoperational quality of life of patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Neuroendocrine/therapy , Cholecystectomy/methods , Gallbladder Neoplasms/therapy , Mixed Tumor, Malignant/therapy , Neoplasm Recurrence, Local/therapy , Carcinoma, Neuroendocrine/diagnosis , Carcinoma, Neuroendocrine/pathology , Female , Gallbladder/diagnostic imaging , Gallbladder/pathology , Gallbladder/surgery , Gallbladder Neoplasms/diagnosis , Gallbladder Neoplasms/pathology , Humans , Middle Aged , Mixed Tumor, Malignant/diagnosis , Mixed Tumor, Malignant/pathology , Neoplasm Recurrence, Local/diagnostic imaging , Tomography, X-Ray Computed , Treatment Outcome
3.
Cesk Patol ; 54(2): 63-71, 2018.
Article in English | MEDLINE | ID: mdl-30441965

ABSTRACT

The main indications for intraoperative consultation of gastrointestinal tract, liver, and pancreatobiliary system are to evaluate the resection margin and to make a tissue diagnosis of lesions for which preoperative histology is not aviable for various reasons. Special situations include the evaluation of liver donor biopsies for the presence of steatosis and inflamation, or determination that ganglion cells are present in the bowel wall at the level where the anastomosis will be placed in case of Hirschprung's disease. The most worrisome pitfalls include differentiating pancreatic ductal carcinoma from chronic pancreatitis, distinguishing biliary tree and gallbladder carcinoma from reactive changes caused by inflammation, and recognizing the presence of diffuse adenocarcinoma at the resection margin of the esophagus and stomach. Keywords: frozen section - gastrointestinal tract - liver - gallbladder - extrahepatic biliary tree - pancreas.


Subject(s)
Biliary Tract , Frozen Sections , Gastrointestinal Diseases , Gastrointestinal Tract , Biliary Tract/pathology , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/pathology , Gastrointestinal Tract/pathology , Humans , Liver
4.
Cesk Patol ; 54(2): 86-92, 2018.
Article in English | MEDLINE | ID: mdl-30441968

ABSTRACT

The introduction of a screening system for Lynch syndrome in pathology laboratories in Plzen yielded 24 diagnoses of Lynch syndrome during the period of 2013-2016, 20 of them presenting with colorectal cancer. In 8 of those 24 cases germline mutations of MMR genes, previously not recognized as pathogenic with certainty, were detected. Although the frequency of Lynch syndrome in patients with colorectal cancer was only 0.34 % in total, following introduction of the universal immunohistochemical investigation of MMR (mismatch repair) proteins expression in all colorectal cancers examined in Sikl´s Institute of Pathology the frequency per year in this department reached 2.4 %. The results favor universal immunohistochemical screening for Lynch syndrome in colorectal and endometrial cancer cases over a selective approach based on a combination of clinical and morphological criteria. Increased effectiveness of the universal approach is not brought about only by higher sensitivity of the immunohistochemical examination per se, but also by the possibility of automation of the process leading to increased adherence even of pathologists not directly engaged in Lynch syndrome management. However, the introduction of a nation-wide universal screening system requires support from the government and health insurance companies. Keywords: colorectal cancer - endometrial cancer - immunohistochemistry - Lynch syndrome - MMR - screening.


Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis , Colorectal Neoplasms , Germ-Line Mutation , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , DNA Mismatch Repair , Humans , Immunohistochemistry , MutL Protein Homolog 1
5.
Anticancer Res ; 38(7): 4159-4167, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29970545

ABSTRACT

BACKGROUND/AIM: Tumour-infiltrating lymphocytes (TILs) and Granzyme B play crucial roles in immune reactions against colorectal carcinoma (CRCa). The inhibitor of Granzyme B is Serpin B9. The aim of this study was to evaluate the effect of immunohistological parameters of TILs on the prognosis of CRCa and presence of lymph node metastasis. PATIENTS AND METHODS: A total of 152 patients who underwent surgery for CRCa were analyzed, including 63 patients in cohort stage II, according to the Union for International Cancer Control (UICC), and 89 patients in cohort UICC stage III. The TIL pattern was classified as peritumoural (PTL), intratumoural (ITL), intrastromal (ISL) or Crohn-like, and immunohistological staining of TIL and cancer cells was also performed. RESULTS: A significantly higher density of CD8+ and CD4+ TILs was observed in the UICC II group, and significantly higher densities of CD4+ TILs were observed in the UICC II group in all distinguished patterns. In the same cohort, higher numbers of CD57+ cells and FoxP3+ TILs and Granzyme B levels were observed. In cohort UICC III, there was a higher density of ISL, PTL CD8+, CD25+ TILs and cancer cells showed staining for Serpin B9. CD57, Granzyme B and CD8 were demonstrated as positive prognostic factors of overall survival, and CD57 and CD4+ TILs were demonstrated as positive prognostic factors of recurrence. CONCLUSION: TILs and CD57 are promising prognostic factors of CRCa. The association of Serpin B9 with lymph node metastasis reveals a potential mechanism for tumour resistance to immune reaction.


Subject(s)
Biomarkers, Tumor/immunology , Colorectal Neoplasms/immunology , Colorectal Neoplasms/pathology , Lymphatic Metastasis/immunology , Lymphatic Metastasis/pathology , Lymphocytes, Tumor-Infiltrating/immunology , Aged , Aged, 80 and over , Female , Humans , Male
6.
Cesk Patol ; 54(1): 23-26, 2018.
Article in Czech | MEDLINE | ID: mdl-29631408

ABSTRACT

Anti-HER2 monoclonal antibody trastuzumab remains the only targeted therapy of gastric carcinoma based on histopathological predictive diagnostics used in current routine clinical practice. In the Czech Republic only the adenocarcinomas with HER2 immunohistochemical score of 3+, together with HER2 amplification detected with in situ hybridization are indicated for treatment with trastuzumab. There has been recent progress in our understanding of the molecular biology of gastric cancer, the role of its tumor microenvironment and vascular supply points to PD-1/PD-L1 and VEGFR2 as possible future targets of targeted therapy. Unfortunately, the interpretation of the results of pharmacological studies, as well as establishing new algorithms of predictive diagnostics are complicated by insufficient molecular stratification of tumors enrolled in the study groups.


Subject(s)
Adenocarcinoma , Stomach Neoplasms , Adenocarcinoma/diagnosis , Adenocarcinoma/genetics , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Receptor, ErbB-2 , Stomach Neoplasms/diagnosis , Stomach Neoplasms/genetics
7.
Cesk Patol ; 53(4): 175-180, 2017.
Article in Czech | MEDLINE | ID: mdl-29227121

ABSTRACT

The literature is reviewed regarding of a rare molecularly defined group of sarcomas with rearrangement of both CIC and BCOR genes, which were originally placed into the EWSR1wt Ewing-like category. Personal experience with three cases demonstrating difficulties of this issue is added. Both groups of lesions differ not only by age and topography, but also vary in both the prognostic and the predictive parameters. CIC-rearranged tumors are very aggressive and almost never occur in the skeleton; in contrary, the BCOR-rearranged ones are predominantly bone tumors in young males behaving even better than classical Ewing sarcoma. From the morphologic point of view, it turned out to be a salient finding that these types of neoplasm might leave canonical morphotype of small blue round cell sarcoma. Instead of it, they are not uncommonly characterized as a relatively uniform spindle cell proliferation with prevailing myxoid transformation deserving much broader differential diagnosis. Our three cases reports display difficulties in reaching the correct diagnosis even by implementing sophisticated molecular techniques in routine practice. Notwithstanding of exhaustive molecular assays used, one may still encounter a lesion where original descriptive term Ewing-lie sarcoma remains uncorrected.


Subject(s)
Gene Rearrangement , Sarcoma, Ewing , Sarcoma, Small Cell , Soft Tissue Neoplasms , Biomarkers, Tumor , Humans , Male , Oncogene Proteins, Fusion/genetics , Proto-Oncogene Proteins/genetics , Repressor Proteins/genetics , Sarcoma, Ewing/diagnosis , Sarcoma, Ewing/genetics , Sarcoma, Small Cell/diagnosis , Sarcoma, Small Cell/genetics , Soft Tissue Neoplasms/diagnosis , Soft Tissue Neoplasms/genetics
8.
Cesk Patol ; 53(4): 185-187, 2017.
Article in Czech | MEDLINE | ID: mdl-29227122

ABSTRACT

Hamartoma of mature cardiac myocytes (HMCM) is a rare benign pseudoneoplastic myocardial lesion. We describe a case of 39-year-old Bulgarian woman living in the Czech Republic, who died because of rupture of anterior communicating artery aneurysm, and severe bronchopneumonia. An incidental finding at the autopsy was a whitish unencapsulated and not sharply demarcated tumor of the left ventricle and adjacent area of interventricular septum, which protruded above the plane of section. Microscopically the tumor consisted of various different forms of disorganized hypertrophic mature cardiac myocytes without vacuolization of cytoplasm, focally in a "herringbone" pattern. Dilated venules and thickened intramural coronary arteries, and intervening bands of connective tissue were present between cardiomyocytes in the tumor. Immunohistochemical staining of MIB1 for the detection of proliferative activity was completely negative. No inflammatory infiltration, adipose tissue or calcifications were present in the tumor.


Subject(s)
Hamartoma , Heart Neoplasms , Myocytes, Cardiac , Adult , Autopsy , Female , Hamartoma/diagnosis , Heart Neoplasms/diagnosis , Humans , Myocardium
9.
Virchows Arch ; 471(3): 393-400, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28730538

ABSTRACT

There is a group of lesions in the head and neck region derived from branchial arches and related structures which, when inflamed, are characterized by the formation of cysts lined by squamous or glandular epithelium and surrounded by a heavy inflammatory infiltrate rich in germinal centers. In the thyroid, the main source of various structures which may cause diagnostic dilemma is the ultimobranchial body. To investigate the spectrum of such thyroid lesions, the consultation files were reviewed for thyroid samples containing pathological structures regarded to arise from the ultimobranchial body. Positive reaction with antibodies against CK5/6, p63, galectin 3, and CEA, and negative reaction with antibodies against thyroglobulin, TTF-1, and calcitonin were used to confirm the diagnosis. The specific subtype of the ultimobranchial body-derived lesion was then determined based on histological examination of H&E-stained slides. Twenty-one cases of ultimobranchial body-derived lesions were retrieved from the consultation files, 20 of them along with clinical information (M/F = 6/14, mean age 55 years, range 36-68 years). Lesions derived from the ultimobranchial body were classified as follows: (hyperplastic) solid cell nests (nine cases), solid cell nests with focal cystic change (five cases), cystic solid cell nests (two cases), branchial cleft-like cyst (four cases), and finally a peculiar Warthin tumor-like lesion (one case). We suggest that the common denominator of these structures is that they all arise due to activation of inflammatory cells around the vestigial structures, which leads to cystic dilatation and proliferation of the epithelial component.


Subject(s)
Branchial Region/pathology , Thyroid Neoplasms/pathology , Adult , Aged , Female , Humans , Male , Middle Aged , Thyroid Diseases/pathology , Thyroid Gland/pathology
10.
Ann Diagn Pathol ; 26: 23-30, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28038707

ABSTRACT

Conflicting data have been published on the prognostic significance of tumor necrosis in papillary renal cell carcinoma (PRCC). Although the presence of necrosis is generally considered an adverse prognostic feature in PRCC, we report a cohort of 10 morphologically distinct cystic and extensively necrotic PRCC with favorable biological behavior. Ten cases of type 1 PRCC with a uniform morphologic pattern were selected from the 19 500 renal tumors, of which 1311 were PRCCs in our registry. We focused on precise morphologic diagnosis supported by immunohistochemical and molecular-genetic analysis. Patients included 8 men and 2 women with an age range of 32-85 years (mean, 62.6 years). Tumor size ranged from 6 to 14 cm (mean, 9.4 cm). Follow-up data were available in 7 patients, ranging from 0.5 to 14 years (mean, 4 years). All tumors were spherical, cystic, and circumscribed by a thick fibrous capsule, filled with hemorrhagic/necrotic contents. Limited viable neoplastic tissue was present only as a thin rim in the inner surface of the cyst wall, consistent with type 1 PRCC. All cases were positive for AMACR, OSCAR, CAM 5.2, HIF-2, and vimentin. Chromosome 7 and 17 polysomy was found in 5 of 9 analyzable cases, 2 cases demonstrated chromosome 7 and 17 disomy, and 1 case showed only chromosome 17 polysomy. Loss of chromosome Y was found in 5 cases, including 1 case with disomic chromosomes 7 and 17. No VHL gene abnormalities were found. Papillary renal cell carcinoma type 1 can present as a large hemorrhagic/necrotic unicystic lesion with a thick fibroleiomyomatous capsule. Most cases showed a chromosomal numerical aberration pattern characteristic of PRCC. All tumors followed a nonaggressive clinical course. Large liquefactive necrosis should not necessarily be considered an adverse prognostic feature, particularly in a subset of type 1 PRCC with unilocular cysts filled with necrotic/hemorrhagic material.


Subject(s)
Carcinoma, Papillary/diagnosis , Carcinoma, Papillary/pathology , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/diagnosis , Kidney Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Chromosome Aberrations , Female , Humans , Immunohistochemistry/methods , In Situ Hybridization, Fluorescence/methods , Male , Middle Aged , Pathology, Molecular/methods , Prognosis
11.
Appl Immunohistochem Mol Morphol ; 25(2): 117-121, 2017 02.
Article in English | MEDLINE | ID: mdl-26509905

ABSTRACT

Cystic nephroma (CN) and mixed epithelial stromal tumor (MEST) of the kidney have been considered as synonymous terms describing a single nosologic entity in adult patients. Cystic nephroma in pediatric patients (PCN) is, apparently, a completely different nosologic entity. Although the presence of DICER 1 mutations is well established in PCN, nothing is currently known about the DICER 1 gene status in adult MEST/CN. About 33 cases of MEST/CN were selected from the Plzen Tumor Registry; 4 cases were later excluded from the study due to low DNA quality. About 28 of the studied tumors displayed a benign morphology, whereas 1 was diagnosed as a malignant MEST/CN with sarcomatoid differentiation of the stromal component. All 29 samples analyzed using polymerase chain reaction and direct sequencing, including the case with the malignant morphology, were negative for mutation in DICER 1 hot-spot codons 1705, 1709, 1809, 1810, 1813, and 1814. Our results show that MEST/CN has no relation to PCN on a molecular genetic level. On the basis of our findings and the established morphologic differences between PCN and MEST/CN, we conclude that the term CN should be used for pediatric cases only and should be avoided in adult cases of MEST.


Subject(s)
Kidney Neoplasms/pathology , Mutation , Ribonuclease III/genetics , Adult , Aged , Aged, 80 and over , Female , Humans , Kidney Neoplasms/genetics , Male , Middle Aged
12.
Appl Immunohistochem Mol Morphol ; 25(9): 664-667, 2017 Oct.
Article in English | MEDLINE | ID: mdl-26990750

ABSTRACT

The purpose of this study was to test the hypothesis that intestinal lipomas occurring in patients devoid of signs of PDGFRA-mutant syndrome might represent sporadic counterparts of familial lipomatous tumors occurring in the spectrum of tumors associated with PDGFRA mutations. PDGFRA-mutant syndrome may manifest with gastrointestinal stromal tumors, Vanek tumors, fibrous tumors, and lipomatous tumors. Until now there has been no molecular genetic study of PDGFRA mutations in intestinal lipomas published in the world literature. A series of 20 intestinal lipomas were obtained from 17 patients, and mutational analysis of exons 12, 14, and 18 of the PDGFRA gene was performed. None of the 16 analyzable tumors showed mutations in PDGFRA. Thus, PDGFRA mutations probably do not play an important role in the development of sporadic lipomas of the intestines.


Subject(s)
Intestinal Neoplasms/genetics , Lipoma/genetics , Mutation , Receptor, Platelet-Derived Growth Factor alpha/genetics , Exons , Humans
13.
Am J Surg Pathol ; 40(11): 1507-1516, 2016 11.
Article in English | MEDLINE | ID: mdl-27340746

ABSTRACT

We report 50 cases of peculiar histiocytic proliferations occurring in diverse body sites that currently bear various names, including nodular mesothelial/histiocytic hyperplasia, nodular histiocytic aggregates, mesothelial/monocytic incidental cardiac excrescences, reactive eosinophilic pleuritis, histioeosinophilic granuloma of the thymus, and intralymphatic histiocytosis. They can sometimes cause considerable differential diagnostic difficulties by resembling a metastatic carcinoma or Langerhans cell histiocytosis. Several previous publications have established a link between some of these conditions, suggesting that these are merely variations within a histopathologic spectrum, affecting different organs and bearing different names based on a particular location. However, no publication has ever comprehensively addressed all of these lesions together in one study in an attempt to explain and discuss their striking analogy. Having studied a large series of cases we provide evidence that all these lesions share the same morphologic, immunohistochemical, and pathogenetic properties, thus they all represent the same pathologic process and should be referred to as such. Taking into account their typical nuclear features we propose a collective term "histiocytosis with raisinoid nuclei" for this spectrum of conditions.


Subject(s)
Cell Nucleus/pathology , Histiocytosis/pathology , Adult , Aged , Aged, 80 and over , Biomarkers/analysis , Child, Preschool , Female , Humans , Immunohistochemistry , Male , Middle Aged , Young Adult
14.
Virchows Arch ; 469(1): 71-80, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27072821

ABSTRACT

Mucin and mucin-like material are features of mucinous tubular and spindle renal cell carcinoma (MTS RCC) but are rarely seen in papillary renal cell carcinoma (PRCC). We reviewed 1311 PRCC and identified 7 tumors containing extracellular and/or intracellular mucinous/mucin-like material (labeled as PRCCM). We analyzed these using morphological, histochemical, immunohistochemical, and molecular genetic methods (arrayCGH, FISH). Clinical data were available for six of the seven patients (five males and one female, age range 61-78 years). Follow-up was available for four patients (2-4 years); one patient died of widespread metastases. Tumor size ranged from 3 to 5 cm (mean 3.8). Of all cases, histological architecture showed a predominantly papillary pattern. Mucin or mucin-like was extracellular in one, intracellular in three, and both intra/extracellular in three cases. All tumors were positive for AMACR, vimentin, and OSCAR, while CK7 was positive in four. Mucicarmine stain was positive in all cases, PAS in six and Alcian blue in three cases. Five tumors were positive for MUC 1, but none were positive for MUC 2, MUC 4, or MUC 6. In only four cases, genetic analysis could be performed. Gain of chromosomes 7 and 17 was found in two cases; gain of 17 only was found in one case. Loss of heterozygosity of 3p was found in one case together with polysomy of chromosomes 7 and 17. No abnormalities of VHL, fumarate dehydrogenase, and TFE3 genes were detected. We conclude that PRCCM is a rare but challenging subtype of RCC that deserves to be further studied. In all the tumors, the mucin-like material was found in those stained with mucicarmin, but other conventional and immunohistochemical stains did not reveal consistent features of a single mucin. The molecular-genetic profile of these tumors was most consistent with that of typical papillary RCC, although one case had mixed genetic features of papillary and clear RCC. PRCCM has metastatic potential, as evidenced by one case with widespread metastases. It remains to be determined whether PRCCM represents a unique tumor subtype, deserving to be distinguished from other subtypes of PRCC.


Subject(s)
Antigens, Neoplasm/metabolism , Carcinoma, Papillary/pathology , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Mucins/analysis , Aged , Biomarkers, Tumor/analysis , Carcinoma, Renal Cell/metabolism , Female , Humans , Immunohistochemistry/methods , In Situ Hybridization, Fluorescence/methods , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Male , Middle Aged
15.
Cesk Patol ; 52(1): 23-30, 2016.
Article in Czech | MEDLINE | ID: mdl-27108553

ABSTRACT

The topic of non-reflux esophagitides is partially hidden in the shadow cast by the huge and modern entity of gastroesophageal reflux disease. Histological investigation alone is often insufficient to reach the correct diagnosis without a correlation of the microscopic picture with clinical presentation, endoscopic gross appearance, personal and pharmacological history of the patient, results of hematological, serological, immunological and microbiological examinations. Due to their low-prevalence, individual types of non-reflux esophagitides are not routinely encountered in routine biopsies. Furthermore, the plethora of etiological agents present with only a limited range of reaction patterns, and thus a single histological picture may be common for more agents. Conversely, one cause may be associated with more morphological patterns. Due to these circumstances the pathological diagnostic management should follow a settled algorithm to prevent an inadequate narrowing of the histopathologist´s view. Histologic findings forming the base of this algorithm include distribution and type of inflammatory infiltrate, appearance of epithelial changes, and (in some cases) even the presence of causative agent in histological slides.


Subject(s)
Esophagitis/pathology , Esophagitis/etiology , Humans
16.
Appl Immunohistochem Mol Morphol ; 24(7): 521-30, 2016 08.
Article in English | MEDLINE | ID: mdl-26447894

ABSTRACT

The characteristic morphologic spectrum of tubulocystic renal cell carcinoma (TC-RCC) may include areas resembling papillary RCC (PRCC). Our study includes 15 RCCs with tubulocystic pattern: 6 TC-RCCs, 1 RCC-high grade with tubulocystic architecture, 5 TC-RCCs with foci of PRCC, 2 with high-grade RCC (HGRCC) not otherwise specified, and 1 with a clear cell papillary RCC/renal angiomyoadenomatous tumor-like component. We analyzed aberrations of chromosomes 7, 17, and Y; mutations of VHL and FH genes; and loss of heterozygosity at chromosome 3p. Genetic analysis was performed separately in areas of classic TC-RCC and in those with other histologic patterns. The TC-RCC component demonstrated disomy of chromosome 7 in 9/15 cases, polysomy of chromosome 17 in 7/15 cases, and loss of Y in 1 case. In the PRCC component, 2/3 analyzable cases showed disomy of chromosome 7 and polysomy of chromosome 17 with normal Y. One case with focal HGRCC exhibited only disomy 7, whereas the case with clear cell papillary RCC/renal angiomyoadenomatous tumor-like pattern showed polysomies of 7 and 17, mutation of VHL, and loss of heterozygosity 3p. FH gene mutation was identified in a single case with an aggressive clinical course and predominant TC-RCC pattern. The following conclusions were drawn: (1) TC-RCC demonstrates variable status of chromosomes 7, 17, and Y even in cases with typical/uniform morphology. (2) The biological nature of PRCC/HGRCC-like areas within TC-RCC remains unclear. Our data suggest that heterogenous TC-RCCs may be associated with an adverse clinical outcome. (3) Hereditary leiomyomatosis-associated RCC can be morphologically indistinguishable from "high-grade" TC-RCC; therefore, in TC-RCC with high-grade features FH gene status should be tested.


Subject(s)
Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Leiomyomatosis/genetics , Adult , Aged , Chromosomes, Human, Pair 17/genetics , Chromosomes, Human, Pair 7/genetics , Chromosomes, Human, Y/genetics , Female , Humans , In Situ Hybridization, Fluorescence , Male , Middle Aged , Molecular Biology , Von Hippel-Lindau Tumor Suppressor Protein/genetics
17.
Ann Diagn Pathol ; 19(4): 261-8, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26031603

ABSTRACT

Chromophobe renal cell carcinoma (CRCC) with neuroendocrine differentiation (CRCCND) has only recently been described. Eighteen cases of CRCC with morphologic features suggestive of neuroendocrine differentiation were selected from among 624 CRCCs in our registry. The tissues were fixed in neutral formalin, embedded in paraffin, cut into 4- to 5-µm-thick sections, and stained with hematoxylin and eosin. As CRCC with neuroendocrine features, tumors with following morphology were suggested: (1) trabecular/palisading/ribbon-like, gyriform, insular, glandular, and solid pattern; (2) uniform polygonal cells formed in small islets; and (3) cribriform pattern in combination with palisading. Selected cases were further analyzed using immunohistochemistry, electron microscopy, array comparative genomic hybridization, and fluorescence in situ hybridization. Cases were classified as CRCCND or CRCC with neuroendocrine-like features (CRCCND-L) based on the immunohistochemical expression of neuroendocrine markers: CRCCND, 4 cases, age range 49 to 79 years, size ranged from 2.2 to 22 cm, and CRCCND-L, 14 cases, age range 34 to 74 years, size range 3.8 to 16.5 cm. Follow-up information was available for 11 of 18 patients aged 0.5 to 12 years. Two of 4 CRCCNDs showed aggressive clinical course with metastatic spreading. Chromophobe renal cell carcinomas with neuroendocrine differentiation were focally positive for CD56 (4/4), synaptophysin (4/4), chromogranin A (1/4), and neuron-specific enolase (3/4). All 14 CRCCND-Ls were mostly negative or very weakly focally positive for some of the aforementioned markers. All 18 tumors were positive for cytokeratin 7 and CD117. Ultrastructural analysis showed poorly preserved neuroendocrine granules only in 2 of 4 analyzed CRCCNDs. Losses of chromosomes 1, 2, 6, and 10 were found in all analyzable CRCCNDs, whereas multiple losses (chromosomes 1, 2, 6, 10, 13, 17, and 21) and gains (chromosomes 4, 11, 12, 14, 15, 16, 19, and 20) were found in CRCCND-L.


Subject(s)
Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Neuroendocrine Tumors/pathology , Adult , Aged , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/metabolism , Comparative Genomic Hybridization , Diagnosis, Differential , Female , Humans , Immunohistochemistry , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Male , Middle Aged , Neoplasm Metastasis , Neuroendocrine Tumors/genetics , Neuroendocrine Tumors/metabolism
18.
Ann Diagn Pathol ; 19(4): 226-31, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26009022

ABSTRACT

The chromosomal numerical aberration pattern in mucinous tubular and spindle renal cell carcinoma (MTSRCC) is referred to as variable with frequent gains and losses. The objectives of this study are to map the spectrum of chromosomal aberrations (extent and location) in a large cohort of the cases and relate these findings to the morphologic variants of MTSRCC. Fifty-four MTSRCCs with uniform morphologic pattern were selected (of 133 MTSRCCs available in our registry) and divided into 3 groups: classic low-grade MTSRCC (Fuhrman nucleolar International Society of Urological Pathology grade 2), high-grade MTSRCC (grade 3), and overlapping MTSRCC with papillary renal cell carcinoma (RCC) morphology. Array comparative genomic hybridization analysis was applied to 16 cases in which DNA was well preserved. Four analyzable classic low-grade MTSRCCs showed multiple losses affecting chromosomes 1, 4, 8, 9, 14, 15, and 22. No chromosomal gains were found. Four analyzable cases of MTSRCC showing overlapping morphology with PRCC displayed a more variable pattern including normal chromosomal status; losses of chromosomes 1, 6, 8, 9, 14, 15, and 22; and gains of 3, 7, 16, and 17. The group of 4 high-grade MTSRCCs exhibited a more uniform chromosomal aberration pattern with losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22 and without any gains detected. (1) MTSRCC, both low-grade and high-grade, shows chromosomal losses (including 1, 4, 6, 8, 9, 13, 14, 15, and 22) in all analyzable cases; this seems to be the most frequent chromosomal numerical aberration in this type of RCC. (2) Cases with overlapping morphologic features (MTSRCC and PRCC) showed a more variable pattern with multiple losses and gains, including gains of chromosomes 7 and 17 (2 cases). This result is in line with previously published morphologic and immunohistochemical studies that describe the broad morphologic spectrum of MTSRCC, with changes resembling papillary RCC. (3) The diagnosis of MTSRCC in tumors with overlapping morphology (MTSRCC and PRCC) showing gains of both chromosomes 7 and 17 remains questionable. Based on our findings, we recommend that such tumors should not be classified as MTSRCC but rather as PRCC.


Subject(s)
Adenocarcinoma, Mucinous/genetics , Adenocarcinoma/genetics , Carcinoma, Papillary/genetics , Carcinoma, Renal Cell/genetics , Chromosome Aberrations , Kidney Neoplasms/genetics , Adenocarcinoma/pathology , Adenocarcinoma, Mucinous/pathology , Aged , Aged, 80 and over , Aneuploidy , Carcinoma, Papillary/pathology , Carcinoma, Renal Cell/pathology , Chromosomes, Human, Pair 17 , Chromosomes, Human, Pair 7 , Comparative Genomic Hybridization/methods , Diagnosis, Differential , Female , Humans , In Situ Hybridization, Fluorescence , Kidney Neoplasms/pathology , Male , Middle Aged , Neoplasm Grading
19.
Virchows Arch ; 466(3): 313-22, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25544614

ABSTRACT

Xp11.2-translocation renal carcinoma (TRCC) is suspected when a renal carcinoma occurs in young patients, patients with a prior history of exposure to chemotherapy and when the neoplasm has morphological features suggestive of that entity. We retrieved 20 renal tumours (from 17,500 archival cases) of which morphology arose suspicion for TRCC. In nine cases, TFE3 translocation was confirmed by fluorescence in situ hybridisation analysis. In 9 of the remaining 11 TRCC-like cases (7 male, 4 female, aged 22-84 years), material was available for further study. The morphological spectrum was diverse. Six tumours showed a mixture of cells with eosinophilic or clear cytoplasm in tubular, acinar and papillary architecture. One case was high grade with epithelioid, spindle cell and sarcomatoid areas. Another showed tubular, solid, and papillary areas and foci containing spindle cells reminiscent of mucinous tubular and spindle cell carcinoma. The third showed dyscohesive nests of large epithelioid and histiocytoid cells in a background of dense lymphoplasmacytic infiltrate. By immunohistochemistry, keratin AE1/AE3 was diffusely positive in three tumours, while CK7 strongly stained one tumour and another focally and weakly. CD10 and Pax8 were expressed by eight, AMACR and vimentin by seven, CA-IX by four and TFE3 and cathepsin K by two tumours. Of the two TFE3-positive tumours, one showed polysomy of chromosome 7 and the other of 17; they were VHL normal and diagnosed as unclassifiable RCC. Of the seven TFE3-negative tumours, three showed polysomy of 7/17 and VHL abnormality and were diagnosed as combined clear cell RCC/papillary RCC. One TFE3-negative tumour with normal 7/17 but LOH 3p (VHL abnormality) was diagnosed as clear cell RCC. One TFE3-negative tumour with polysomy 7/17 but normal VHL was diagnosed as papillary RCC, and two with normal chromosomes 7/17 and VHL gene were considered unclassifiable. As morphological features and IHC are heterogeneous, TRCC-like renal tumours can only be sub-classified accurately by multi-parameter molecular-genetic analysis.


Subject(s)
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Carcinoma, Renal Cell/classification , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/classification , Kidney Neoplasms/genetics , Translocation, Genetic/genetics , Adult , Aged , Aged, 80 and over , Algorithms , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism , Carcinoma, Renal Cell/diagnosis , Chromosomes, Human, Pair 17/genetics , Chromosomes, Human, Pair 7/genetics , Diagnosis, Differential , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Humans , In Situ Hybridization, Fluorescence , Kidney/metabolism , Kidney/pathology , Kidney Neoplasms/diagnosis , Male , Middle Aged , Molecular Biology , Retrospective Studies
20.
Ann Diagn Pathol ; 18(6): 351-7, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25438924

ABSTRACT

UNLABELLED: t(6;11) renal cell carcinoma (RCC) has been recognized as a rare and mostly nonaggressive tumor (NAT). The criteria for distinguishing aggressive tumors (AT) from NATs are not well established. A total of 6 cases were selected for the study. Five cases of t(6;11) RCCs behaved nonaggressively, and 1 was carcinoma with aggressive behavior. The tumors were analyzed morphologically using immunohistochemistry and by molecular-genetic methods. The specimen of aggressive t(6;11) RCC was from a 77-year-old woman who died of the disease 2.5 months after diagnosis. The specimens of nonaggressive t(6;11) RCCs were from 3 women and 2 men whose ages range between 15 and 54 years. Follow-up was available in all cases (2.5 months-8 years). The tumor size ranged from 3 to 14 cm in nonaggressive t(6;11) RCC. In the aggressive carcinoma, the tumor size was 12 cm. All tumors (6/6) were well circumscribed. Aggressive t(6;11) RCC was widely necrotic. Six (100%) of 6 all tumors displayed a solid/alveolar architecture with occasional tubules and pseudorosettes. Pseudopapillary formations lined by bizarre polymorphic cells were found focally in the aggressive t(6;11) RCC case. Mitoses, though rare, were found as well. All cases (AT and NAT) were positive for HMB-45, Melan-A, Cathepsin K, and cytokeratins. CD117 positivity was seen in 4 of 5 NATs, as well as in the primary and metastatic lesions of the AT. mTOR was positive in 2 of 5 NATs and vimentin in 4 of 5 NATs. Vimentin was negative in the primary lesion of the AT, as well as in the metastasis found in the adrenal gland. Translocation t(6;11)(Alpha-TFEB) or TFEB break was detected in 4 of 5 NATs and in the AT case. Aggressive tumor showed amplification of TFEB locus. Losses of part of chromosome 1 and chromosome 22 were found in 1 of 5 NATs and in the AT. CONCLUSIONS: (1) Aggressive t(6;11) RCCs generally occur in the older population in comparison with their indolent counterparts. (2) In regard to the histologic findings in ATs, 3 of 5 so far published cases were morphologically not typical for t(6;11) RCC. Of the 3 cases, 2 cases lacked a small cell component and 1 closely mimicked clear cell-type RCC. (3) Necroses were only present in aggressive t(6;11) RCC. (4) Amplification of TFEB locus was also found only in the aggressive t(6;11) RCC.


Subject(s)
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Carcinoma, Renal Cell/genetics , Chromosomes, Human, Pair 11/genetics , Chromosomes, Human, Pair 6/genetics , Kidney Neoplasms/genetics , Translocation, Genetic , Adolescent , Adult , Age Factors , Aged , Carcinoma, Renal Cell/pathology , Female , Humans , Kidney Neoplasms/pathology , Male , Middle Aged , Young Adult
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