Showing papers in "Československá patologie in 2015"

Celiac disease-like enteropathy due to antihypertensive therapy with the angiotensin-II receptor type 1 inhibitor eprosartan

Abstract: An 83-year-old woman with hypertension received the angiotensin-II receptor type 1 blocker (ARB) eprosartan for more than 10 years. Six months ago, the dosage of the drug was doubled, and the patient reported a sudden onset of diarrhea. Duodenal biopsies showed a celiac disease-like pathology with flattened mucosa and an increase of intraepithelial lymphocytes and eosinophils, but serology of celiac disease remained negative. Celiac disease-like changes have been previously reported to be associated with other ARBs. This is the first case following eprosartan medication. In celiac-disease-like pathology of the small bowel with negative serology, drug-induced changes, for example due to ARBs, should be excluded.

EGFR in triple negative breast carcinoma: significance of protein expression and high gene copy number

Abstract: SUMMARY Background: As up to 60 % of triple negative breast carcinomas are reported to express EGFR, the receptor is a potential target for biological therapy. The exact role EGFR plays in triple negative breast carcinoma (TNBC) biology, however, remains uncertain. We aimed to discover associations between EGFR protein expression as well as gene copy number changes and clinico-pathologic TNBC characteristics. Methods: We performed an immunohistochemical and dual in situ hybridization study on a set of 52 archive cases of pre-treatment TNBC in order to detect EGFR protein expression and EGFR gene copy number changes. Clinico-pathologic and follow up data were compared with EGFR status for determining possible links between EGFR and tumor characteristics and/or behavior. Results: 88.5 % of our cases showed EGFR expression. We found no significant links between EGFR expression and tumor grade (p = 0.204), lymph node status (p = 0.514) or p53 status (p = 0.078). Though EGFR gene amplification (EGFR gene:chromosome 7 ratio ≥ 2) was rare (1.9 % of all cases), a high gene copy number (≥ 4 copies per cell) was observed in 15.4 % of all cases. High EGFR gene copy number appeared to be more common in non-ductal, ‘special-type’ carcinomas than in ductal carcinomas. Neither EGFR expression nor EGFR gene copy number was associated with event-free survival. Conclusion: EGFR changes do not appear to be associated with markers of aggressive behavior in TNBC. Further studies with much larger sample sizes are essential in understanding the role EGFR plays in TNBC biology in order to identify the patients that could benefit from EGFR targeted therapy.

Pyloric gland adenoma: a histologic, immunohistochemical and molecular genetic study of 23 cases

Abstract: Pyloric gland adenoma is a rare neoplasm with a gastric epithelial differentiation. We report 23 cases of pyloric gland adenoma in older persons, with a mean age of 74 years (range 52 - 87 years). They occurred in the esophagus (3 cases), corporal gastric mucosa (7 cases), duodenum (10 cases), gallbladder (2 cases), and choledochus (one case). Histologically, they were characterized by closely packed pyloric gland-type tubules with a monolayer of cuboidal to low columnar epithelial cells containing basally located round nuclei, and a superficial layer of tall, columnar, foveolar-type epithelium. Immunohistochemically, most tumor glands expressed pyloric gland mucin MUC6, whereas MUC5AC was positive in superficial gastric foveolar epithelium, and in a minority of glands. In addition, scattered neuroendocrine cells positive for chromogranin A and/or synaptophysin were seen in all cases. In 3 cases (two cases in the gallbladder and one case in the esophagus), areas of intestinal metaplasia with CK20, CDX2, and MUC2 positivity were found. Focal low-grade dysplasia was found in five cases (21.7%), and diffuse high-grade dysplasia was seen in one adenoma (4.4%), i.e., 6 of 23 PGAs (26.1%) showed dysplastic features. In one esophageal case, an invasive adenocarcinoma was diagnosed. Scattered p53 positive cells were found in all cases. Their number was higher in lesions with low-grade dysplasia and it was substantially increased in adenoma with high-grade dysplasia and in adenocarcinoma. Our molecular genetic results indicate that pyloric gland adenomas neoplastic nature is associated with p53 accumulation, mutations in oncogenes GNAS, KRAS, CTTNB1 and tumor suppressor genes SMAD4, and TP53. Pyloric gland adenoma can evolve into dysplasia and adenocarcinoma.

Infections after kidney transplantation

Abstract: Immunosuppressed kidney transplant recipients are at risk for a variety of infectious complications and more than half of them suffered from this complication in the early post-transplant period. Despite the fact that the long term risk of serious infectious complications in the early postoperative period decreased, remain the infection the most frequent cause of morbidity in the first 6 months after transplant. It is important to realize that the clinical manifestations of infection in the compromised host are variable and often atypical. In the later period, infections that affect the kidney graft become clinically important, and some of them occur only in immunosuppressed patients. Here we will discuss polyomavirus nephropathy which represents the most important and most frequent viral disease of renal allografts.

[A revolution postponed indefinitely.WHO classification of tumors of the breast 2012: the main changes compared to the 3rd edition (2003)].

Abstract: In 2012, the new classification of the fourth series WHO blue books of breast tumors was released. The current version represents a fluent evolution, compared to the third edition. Some limited changes regarding terminology, definitions and the inclusion of some diagnostic units were adopted. The information about the molecular biology and genetic background of breast carcinoma has been enriched substantially.

[Molecular pathology of endometrial carcinoma - a review].

Abstract: Endometrial carcinoma (EC) is the most common malignancy of the female genital tract in developed countries. According to its histomorphologic characteristics EC is divided into endometroid and serous carcinoma; among less common subtypes there are clear cell, mucinous, neuroendocrine and undifferentiated carcinoma and carcinosarcoma. Endometroid and serous EC were essential for the so-called dual classification of EC (type I and type II), which considered mainly epidemiological, clinical and endocrine characteristics. It was shown that part of the high-grade serous carcinomas (type II) can develop from the endometroid EC by a multiplication of genomic changes and there are also EC, in which both basic types are overlapping. Today it is known that clinical and histological presentation of the EC reflects the genetic and epigenetic alterations affecting mainly PTEN, PIK3CA, KRAS, CTNNB1 and TP53 genes, or leading to microsatellite instability. However, these changes are variably present in both types of EC; therefore dual division of EC has appeared very rigid. The novel classifications should represent an integrated system which also incorporates the results of the gene expression analyses and multiparallel DNA sequencing. Based on these findings EC were divided into four molecular categories: a) POLE/ultra mutated; b) hyper mutated microsatellite instable; c) "copy number low" d) "copy number high" serous-like carcinoma. This division better reflects the biological characteristics of each EC and represents a base for the individual therapy.

Shadow cell differentiation in endometrioid carcinomas of the uterus. Its frequent occurrence and beta-catenin expression.

Abstract: Shadow cell differentiation (SCD) is typical for pilomatrixoma and related follicular tumors of the skin. However, it has been described rarely in some extra-cutaneous lesions such as gonadal teratoma, craniopharyngioma, odontogenic cyst, and in rare visceral carcinomas (lung, bladder, gallbladder, uterus, ovary, and colon). In our practice, we have noticed that the occurrence of shadow cells is not very rare in endometrioid carcinoma (EC) of the uterus. For exact determination of SCD in these tumors, we reviewed 59 consecutive cases of uterine EC. The series included curettage and hysteroscopic specimens. We have found SCD in 9 (15.3 %) of the tumors. In these cases, the age of the patients and FIGO grade did not differ significantly from other ECs. Immunohistochemically, all ECs with SCD showed nuclear expression of beta-catenin in areas of SCD, indicating a possible role of the Wnt signaling pathway in tumorigenesis as well as a role of nuclear accumulation of beta-catenin by trans-differentiation from glandular toward squamous and shadow cell phenotypes. We have found that the relatively frequent presence of SCD in ECs can assists in the diagnosis of these tumors.

[Neurofibromatosis von Recklinghausen type 1 (NF1) - clinical picture and molecular-genetics diagnostic].

Abstract: Neurofibromatosis von Recklinghausen type 1 (NF1) is a multisystem, autosomal dominant hereditary neurocutaneous disease characterized by skin, central and peripheral nervous system , eyes , bone, endocrine, gastrointestinal and blood vessel wall involvement. It has an estimated frequency of 1 in 3000. Neurofibromatosis type 1 is caused by mutations in the large NF1 gene located on chromosome 17q11.2, encoding the cytoplasmic protein neurofibromin. It is expressed in multiple cell types but is highly expressed in Schwann cells, oligodendrocytes, neurons, astrocytes and leukocytes. Neurofibromin is known to act as a tumor suppressor via Ras-GTPase activation, which causes down-regulation of cellular signaling via the Ras/mitogen-activated protein kinase (MAPK) pathway. Failure of this function is associated with a tendency to form tumors which are histologically hamartomas as well as benign tumors. Tumors of the central nervous system include low-grade gliomas (pilocytic astrocytomas grade I), especially optic pathway gliomas. They are often clinically asymptomatic. Other intracranial tumors are in the brain stem and also elsewhere in the brain and spinal cord. Hydrocephalus may be a complication of NF1 gliomas or due to stenosis of the distal part of the aqueduct Silvii. Cutaneous and subcutaneous neurofibromas or plexiform neurofibromas are localized in the peripheral nervous system. Plexiform neurofibromas have a significant lifetime risk of malignancy. The clinical diagnosis of NF1 is defined by diagnostic criteria. The NF1 diagnosis is satisfied when at least two of the seven conditions are met. The method of direct DNA analysis of large NF1 gene (61 exons) is available. The results of studies of genotype - phenotype established few correlations. But predicting the disease by finding mutations is not currently possible. NF1 exhibits a wide range of variability of expression and complete penetrance, even within the same family. About half of cases are new mutations. The treatment of patients with neurofibromatosis is symptomatic. Central nervous system symptomatic low-grade gliomas are most often treated with chemotherapy. For plexiform neurofibromas surgical removal is currently the only treatment option.

Pathological evaluation of colorectal cancer specimens: advanced and early lesions

Abstract: Surgical resection is the treatment of choice for patients with locally confined disease, but early cancers may be adequately treated by endoscopic resection alone. In advanced colorectal cancers, accurate staging including pathological lymph node assessment is crucial for patient counselling and decision making. In addition to the extent of surgical lymph node removal and the thoroughness of the pathologist in dissecting the cancer specimen lymph node recovery is related to the actual number of regional lymph nodes that is related to patient demographics, tumor location and biology. Current guidelines recommend a minimum of twelve nodes harvested as the standard of care. In patients with node-negative tumors a variety of histological features may be used for adjusted risk assessment, including histological subtyping, lymphatic and venous invasion, tumor budding and tumor necrosis as well as the anti-tumor host inflammatory response which has been identified as favorable feature in several studies. In rectal cancer, involvement of the circumferential resection margin and the plane of surgery are important prognostic factors. Early or superficial colorectal cancer is defined as invasive adenocarcinoma invading into, but not beyond the submucosa. A number of features require special attention because they are used to determine the necessity for radical surgery. In addition to the assessment of completeness of excision, these include the recording of parameters that predict the presence of lymph node metastasis, namely the depth of invasion into the submucosa, tumor grade, and the presence of additional risk factors, such as angioinvasion and tumor budding. The combination of these parameters allows the stratification of affected individuals into low-risk and high-risk categories.

[Melanocytic matricoma--a case report].

Abstract: A rare skin tumor (melanocytic matricoma), 6 mm in diameter, was diagnosed on the skin of the back in a 66-year-old man. It was composed of two cellular types: 1. epithelial cells with hair follicle differentiation and 2. dendritic melanocytes. After two years of follow-up there are no signs of a relapse or generalisation of the tumor.

Four bilateral synchronous benign and malignant kidney tumours: a case report.

Abstract: UNLABELLED Synchronous occurrence of benign and malignant kidney tumours is very rare. We present the case of a 63-year-old female patient who underwent a bilateral partial nephrectomy after being diagnosed with bilateral kidney tumours by ultrasonography and a computed tomography scan. Histopathological analysis of the left kidney tumour mass revealed a chromophobe renal cell carcinoma. In the right kidney specimen clear cell renal cell carcinoma was found along with a small angiomyolipoma and renomedullary interstitial cell tumour. There were no indications for subsequent chemotherapy. At present, three years after the surgery, the patient has had no signs of relapse and maintains normal renal function. KEYWORDS bilateral kidney tumours - renal cell carcinoma - angiomyolipoma.

[Neuroendocrine tumor of the breast--metastasis or primary breast carcinoma? Case report].

Abstract: A 74-year-old women with a history of neuroendocrine tumor in the terminal ileum presented on screening mammography with an irregular hypoechogenic mass in the upper outer quadrant of the left breast. A core biopsy showed a neuroendocrine tumor, interpreted as a probable metastasis from the intestinal primary. Other masses were found in the right lobe of the liver. Resection of the masses in the breast and liver was performed at the same time. Morphological and immunohistochemical findings (positive neuroendocrine markers, estrogene receptors and negative cytokeratine 7, mammaglobin, GCDFP-15, cytokeratine 20 and progesterone receptors) were consistent with a diagnosis of a metastatic well-differentiated neuroendocrine tumor, despite some estrogen receptor positivity. Issues of primary and metastatic breast neuroendocrine tumors are discussed in detail.

Hopes and pitfalls of the molecular classification of breast cancer

Abstract: Traditional histopathological diagnosis of breast cancer has been extended in recent years through the results of additional methods. Today, the results of the detection of hormone receptors, HER-2/neu, and Ki67 antigen are thus an integral part of the histopathological diagnosis. A critical factor for the success of these tests is the fulfillment of pre-analytical phase conditions - i.e. optimal fixation, as well as taking into account the heterogeneous nature of the neoplastic population. In addition to the above-mentioned markers - which have become a routine practice in recent years, there are many efforts to include the molecular characteristics of tumors both in tumor classification as well as in the prediction of results of cancer treatment. Most of the work is based on the use of gene expression profiles. On the basis of the detection of increased or decreased expression of a large number of genes, it is possible to find a set of multiple genes correlating with the biological behavior of the tumor. Using this approach, four basic subgroups of breast cancer have been identified - luminal, basal-like, HER-2 enriched and normal gland-like. Over the course of time, the number of molecular categories has expanded - originally a homogenous group of luminal cancers has been subclassified into the luminal A, B and C. Also within basal-like carcinomas additional subgroups have been identified. However, the results of studies dealing with the analysis of gene expression profiles suggest that our understanding of the biology of breast cancer is far from being complete. The individual categories are defined differently in various publications and thus the comparison of the results of these studies is very difficult. Another approach for the molecular classification of breast cancer is the immunohistochemical detection of various proteins used as a surrogate marker instead of the detection of the mRNA of individual genes. The advantage of this approach is the possibility to use even archive material, as well as much lower costs. On the other hand, its main limitation is the inability of parallel detection of thousands of markers, unlike in genomic profiling. The results of molecular classification are, however, not fundamentally surprising. The fact that breast cancer tumor stem cells can differentiate towards myoepithelial (or basal) and luminal cells has been known for a long time. These two lines of differentiation are - among others - characterized by differential expression of cytoskeletal proteins as well as of other molecules. These findings have been confirmed by the results of molecular studies - either those based on gene expression profiling or immunohistochemical ones. Research results in gene expression profiling have relatively quickly translated into clinical practice. At present, several commercially available certified tests serve as a complementary source of information for decisions about clinical treatment.

Surgical techniques of organ transplants

Abstract: The list of surgical procedures of solid organ transplantations appears very interesting and colorful, even with overlap among techniques. Liver transplantation is a life-saving procedure in a majority of cases, the liver can be transplanted as a full or partial graft. The liver graft can be split for two recipients; it can also be reduced for a small recipient if splitting is not indicated. Kidney transplantation is the most common solid organ transplant procedure, the majority of kidney grafts come from brain-dead donors whereas the number of live donor transplants is increasing, also thanks to paired donation and blood group incompatible transplantation methods. The small bowel and multivisceral transplantation are rare procedures; they serve selected patients with short bowel syndrome, some patients with retroperitoneal tumors or with extensive visceral thrombosis. Solid organ transplants are well established treatment methods with good and proven outcomes. A majority of patients can return to a normal life after their transplants.

[Microvascular density in lymphomas - evaluation methods and clinical impact].

Abstract: In recent years antiangiogenic therapy has become a part of treatment protocols of solid tumors as well as of lymphomas. This is why tumor vascularization has been explored, the most important parameters to describe it being the microvascular density and immunohistochemical assessment of the expression of VEGF (vascular endothelial growth factor) and of its receptors. This review summarizes various methods of assessment of the microvascular density and the prognostic impact of microvascular density in lymphomas.

[Small cell type (Ewing-like) clear cell sarcoma of soft parts: a case report].

Abstract: The authors present a unique case of small cell variant of clear cell sarcoma of soft parts in a 42-year old woman. The tumor originally arose in the right flank of the soft tissues and ultimately developed both a local recurrence and multiple distant skin metastases two years and ten months thereafter. Nonspecific morphology of small blue round cell tumor was preserved at all microscopically verified sites and initially led to the spectrum of erroneous diagnoses such as an extraskeletal myxoid chondrosarcoma, Ewing sarcoma as well as malignant melanoma. The distinctive features of clear cell sarcoma such as fascicular nested growth pattern, spindling, clear cell change and/or eosinophilic cytoplasm were not disclosed even by extensive sampling. Immunohistochemically, the tumor expressed only S100protein and HMB45; all other markers (CD99, FLI1, cytokeratins, EMA) were completely negative. The molecular analysis carried out in one of the cutaneous metastases revealed translocation t(12;22) (EWSR1-ATF1) and ultimately led to the correct diagnosis of unusual Ewing-like clear cell sarcoma. Discussed is the implementation of molecular tests in routine diagnostics considering the existence of both histologically and biologically different tumors with an identical pathogenic molecular background.

Mammary fibroadenoma with pleomorphic stromal cells.

Abstract: UNLABELLED The presence of enlarged and pleomorphic nuclei is usually regarded as a feature of malignancy, but it may on occasion be seen in benign lesions such as mammary fibroadenomas. We present such a case of fibroadenoma occurring in a 37-year-old woman presenting with a self-palpable right breast mass. Histological examination of the tumor revealed the presence of multi and mononucleated giant cells with pleomorphic nuclei. The recognition of the benign nature of these cells is necessary for differential diagnosis from malignant lesions of the breast. KEYWORDS fibroadenoma - pleomorphic stromal cells - atypia - breast.