Professor Jaroslav Hlava and his successors - a remembrance on the occasion of the 100th anniversary of the opening of the Hlava institute.

This year marks the 100th anniversary of the opening of the Hlava institute, which was ceremoniously held on April 18, 1921. The opening of the institute was the result of many years of Professor Hlava´s efforts to provide a dignified space for pathology at the Czech university. Hlava fundamentally influenced Czech pathology and was undoubtedly one of the most important personalities of not only Czech and European pathology, but the entire field of Czech medicine of the period. His influence on pathology and microbiology is indisputable and widely known, but he has also fundamentally influenced other fields, especially oncology. On the occasion of this important anniversary the following entry offers a look at the personality of Professor Jaroslav Hlava and provides an overview of his research activities, as well as a complete list of his publications. The successors of Professor Hlava in the position of the head of institute are also briefly listed.

Molecular patterns of diffuse and nodular parathyroid hyperplasia in long-term hemodialysis.

Secondary hyperparathyroidism is a well-known complication of end-stage renal disease (ESRD). Both nodular and diffuse parathyroid hyperplasia occur in ESRD patients. However, their distinct molecular mechanisms remain poorly understood. Parathyroid tissue obtained from ESRD patients who had undergone parathyroidectomy was used for Illumina transcriptome screening and subsequently for discriminatory gene analysis, pathway mapping, and gene annotation enrichment analysis. Results were further validated using quantitative RT-PCR on the independent larger cohort. Microarray screening proved homogeneity of gene transcripts in hemodialysis patients compared with the transplant cohort and primary hyperparathyroidism; therefore, further experiments were performed in hemodialysis patients only. Enrichment analysis conducted on 485 differentially expressed genes between nodular and diffuse parathyroid hyperplasia revealed highly significant differences in Gene Ontology terms and the Kyoto Encyclopedia of Genes and Genomes database in ribosome structure (P = 3.70 × 10-18). Next, quantitative RT-PCR validation of the top differently expressed genes from microarray analysis proved higher expression of RAN guanine nucleotide release factor (RANGRF; P < 0.001), calcyclin-binding protein (CACYBP; P < 0.05), and exocyst complex component 8 (EXOC8; P < 0.05) and lower expression of peptidylprolyl cis/trans-isomerase and NIMA-interacting 1 (PIN1; P < 0.01) mRNA in nodular hyperplasia. Multivariate analysis revealed higher RANGRF and lower PIN1 expression along with parathyroid weight to be associated with nodular hyperplasia. In conclusion, our study suggests the RANGRF transcript, which controls RNA metabolism, to be likely involved in pathways associated with the switch to nodular parathyroid growth. This transcript, along with PIN1 transcript, which influences parathyroid hormone secretion, may represent new therapeutical targets to cure secondary hyperparathyroidism.

Apoptosis - associated genes and their role in predicting responses to neoadjuvant breast cancer treatment.

BACKGROUND: Neoadjuvant chemotherapy is used in the treatment of breast carcinoma because it substantially reduces the size of the primary tumor and lymph node metastases. The present study investigated biomarkers that can predict a pathologic response to the therapy. MATERIAL/METHODS: The role of apoptosis in regression of the tumors after neoadjuvant chemotherapy was determined by TUNEL and anti-active caspase 3 assay. The transcriptional profile of 84 key apoptosis genes was evaluated in both pre-therapeutically obtained tumor tissue by core needle biopsy and in specimens removed by final surgery, using a pathway-specific real-time PCR assay. Obtained data were analyzed by hierarchical cluster analysis and correlation analysis. The immunohistochemical profile of each tumor was determined using the standard ABC method. RESULTS: On the basis of a hierarchical cluster analysis of 13 significantly changed genes, we divided patients into good and poor prognosis groups, which correlate well with progression-free survival. In the good prognosis group, we found a statistically significant down-regulation of the expression of MCL1 and IGF1R genes after neoadjuvant treatment. We also found a statistically significant overexpression of BCL2L10, BCL2AF1, CASP8, CASP10, CASP14, CIDEB, FADD, HRK, TNFRSF25, TNFSF8 and CD70 genes. In contrast, we found up-regulation of IGF1R after the treatment in the group with poor prognosis. CONCLUSIONS: Gene expression profiling using real-time PCR assay is a valuable research tool for the investigation of molecular markers, which reflect tumor biology and treatment response.

Correlation of dynamic impact testing, histopathology and visual macroscopic assessment in human osteoarthritic cartilage.

OBJECTIVE: Improved staging of cartilage degeneration is required, particularly during the early stages. We correlated mechanical properties with histological and macroscopic findings. METHODS: One hundred and twenty cartilage samples were obtained during total knee arthroplasty. Two adjacent plugs were harvested--one for histological classification and one for macroscopic and biomechanical purposes. Dynamic impact testing was performed; normal stress, dissipated energy (∆E), tangent modulus and stiffness were evaluated. RESULTS: Samples were classified according to six categories of the ICRS histological scale. Mechanical characteristics revealing significant differences between the groups (p < 0.01) were specific damping and related absolute ∆E. A significant correlation was found between the macroscopic score and specific damping, as well as absolute and relative ∆E (p < 0.01). A strong relation was revealed between relative ∆E and cartilage thickness (p < 0.001; R (2) = 0.69). CONCLUSIONS: Only ∆E correlated with the condition of the cartilage--the value increased with decreasing quality-and is the most suitable characteristic. This change appears substantial in initial stages of cartilage deterioration.

[KRAS mutation testing in therapeutic algorithm for treatment of metastatic colorectal carcinoma]. / Vysetrení mutacního statutu genu KRAS jako soucást algoritmu lécby metastatického kolorektálního karcinomu.

Targeted therapy has become an integral part of treatment procedures of malignant tumors. Colorectal carcinomas are frequently targeted with monoclonal anti-EGFR antibodies (cetuximab and panitumumab). Activating somatic mutations in codons 12 and 13 of the exon 2 of KRAS gene are considered negative predictive factors of response to anti-EGFR therapy in patients with metastatic colorectal cancer. In the Czech Republic, evaluation of mutational status of KRAS gene is performed in several referral laboratories. In 2009, these laboratories performed 2580 tests of the KRAS mutational status--out of these, 60.2% cases reported non-mutated, wild-type KRAS. In one of the referral laboratories, we demonstrate the logistics of KRAS testing procedure. Stratification of patients with metastatic colorectal tumors based on their KRAS mutational status has evolved to a standard procedure. Laboratories performing these methods shall therefore adhere to the recommendations of the professional and accredited societies.

Target-like chondrocytes with thick perichondrocytic rings in cartilage-forming tumours. Preliminary report.

BACKGROUND: Here we present our experience with the occurrence of neoplastic chondrocytes with target-like appearance surrounded with unusual hypertrophic thick eosinophilic perichondrocytic rings (baskets), sometimes containing two or several layers. METHODS AND RESULTS: Pericellular rings (baskets) were positive in APAS and Masson's staining method and showed immunoreactivity with antibody against type IV collagen. Such single cells or small groups of such cells were observed rarely in 3 osteochondromas, 2 skeletal chondromas, 2 extraskeletal chondromas and 2 skeletal and 1 laryngeal chondrosarcomas. Moreover, 1 unusual soft tissue chondrosarcoma was composed entirely of target-like chondrocytes with hypertrophic extremely thick perichondrocytic rings. Such cartilage-forming tumour with target-like cells, which, to the best of our knowledge, is the first such chondrosarcoma reported in the literature. Ultrastructural evidence is presented that perichondrocytic rings have complicated structure.They contained microfibrillar component with abundant admixture of irregular aggregates of dense amorphous non-fibrillar material localised in lacunar spaces. In outer part of the rings predominated microfibrillar structures corresponding to type VI collagen that produced a rather dense capsule-like demarcation line against surrounding intercellular spaces. CONCLUSIONS: The described unusual changes are probably the result of hyperproduction and remodelation of perichondrocytic matrix by abnormal neoplastic chondrocytes in response to unknown factors. Local vascular and molecular signals, may be supposed as probable causes of this phenomenon.

Morphological findings in frozen non-neoplastic kidney tissues of patients with kidney cancer from large-scale multicentric studies on renal cancer.

There are unexplained geographical variations in the incidence of kidney cancer with the high rates reported in Baltic countries, as well as eastern and central Europe. Having access to a large and well-annotated collection of "tumor/non-tumor" pairs of kidney cancer patients from the Czech Republic, Romania, Serbia, UK, and Russia, we aimed to analyze the morphology of non-neoplastic renal tissue in nephrectomy specimens. By applying digital pathology, we performed a microscopic examination of 1012 frozen non-neoplastic kidney tissues from patients with renal cell carcinoma. Four components of renal parenchyma were evaluated and scored for the intensity of interstitial inflammation and fibrosis, tubular atrophy, glomerulosclerosis, and arterial wall thickening, globally called chronic renal parenchymal changes. Moderate or severe changes were observed in 54 (5.3%) of patients with predominance of occurrence in Romania (OR = 2.67, CI 1.07-6.67) and Serbia (OR = 4.37, CI 1.20-15.96) in reference to those from Russia. Further adjustment for comorbidities, tumor characteristics, and stage did not change risk estimates. In multinomial regression model, relative probability of non-glomerular changes was 5.22 times higher for Romania and Serbia compared to Russia. Our findings show that the frequency of chronic renal parenchymal changes, with the predominance of chronic interstitial nephritis pattern, in kidney cancer patients varies by country, significantly more frequent in countries located in central and southeastern Europe where the incidence of kidney cancer has been reported to be moderate to high. The observed association between these pathological features and living in certain geographic areas requires a larger population-based study to confirm this association on a large scale.

[Histopathological classification of idiopathic interstitial pneumonias]. / Histopatologická klasifikace idiopatických intersticiálních pneumonií.

The classification scheme of interstitial lung diseases has undergone numerous revisions. The criteria for distinguishing seven distinct subtypes of idiopathic interstitial pneumonias are now well defined by consensus in the recently published ATS/ERS classification of these lung diseases. In our present review the histological patterns of the different types are described and the differential diagnosis of idiopathic interstitial pneumonias is discussed. Surgical lung biopsy remains the gold standard for the diagnosis of interstitial pneumonias, and sampling from at least 2 sites is recommended. Video-assisted thoracoscopic surgical biopsy is the preferred method for obtaining lung tissue as this procedure offers a similar yield as an open thoracotomy The most common histological subtype of chronic interstitial lung disease is the usual interstitial pneumonia [UIP] which makes up 47-71% of cases. The key histologic features include patchy subpleural and paraseptal distribution of remodeling lung architecture with dense fibrosis, frequent honeycombing, and large fibroblastic foci. Temporal and spatial heterogeneity are the hallmarks. Nonspecific interstitial pneumonia [NSIP] occurs primarily in middle-aged women who have never smoked, with more than 5-years survival rate in 80% of patients. The major feature of NSIP is a uniform interstitial thickening of alveolar septa by a fibrosing or cellular process. The cardinal histological feature in respiratory bronchiolitis and desquamative pneumonia is an excess of intraalveolar histiocytes. In both patterns, there is variable interstitial fibrosis and chronic inflammation, and a strong association with a history of smoking. Organizing pneumonia (idiopathic bronchiolitis obliterans-organizing pneumonia [BOOP]) is not strictly an interstitial process, because the alveoli and bronchioles are filled by intraluminal polyps of fibroblastic tissue and the expansion of the interstitium is mild. Lymphocytic interstitial pneumonia [LIP] is currently viewed as a pattern of diffuse reactive pulmonary hyperplasia associated in most cases with EB virus, immunosuppression, or a connective tissue disorder. Malignant transformation may rarely occur. A dense mixed interstitial lymphoid infiltrate is a typical histological finding. Diffuse alveolar damage [DAD] from unknown causes is termed acute interstitial pneumonia [AIP], and is synonymous with cases of Hamman-Rich disease. Hyaline membranes in the exsudative phase and marked expansion of the interstitium later are present.

Actin expression in neural crest cell-derived tumors including schwannomas, malignant peripheral nerve sheath tumors, neurofibromas and melanocytic tumors.

Tumors that originate from neural crest-derived cells represent a heterogeneous group of neoplasms including benign and malignant tumors with melanocytic and schwannian differentiation. The immunophenotype of these tumors is well known but little is known about the expression of smooth muscle/myofibroblastic markers in these tumors. A total of 590 neural crest-derived tumors (50 benign schwannomas, five malignant peripheral nerve sheath tumors, 80 neurofibromas, 240 nevocytic nevi, 115 primary melanomas, and 100 melanoma metastases) were studied with respect to alpha-smooth muscle actin and muscle-specific actin expression. alpha-Smooth muscle actin and muscle-specific actin-positive tumor cells with a co-expression of S-100 protein were found in one benign schwannoma, one primary cutaneous melanoma, and four melanoma metastases. Four of these cases were examined ultrastructurally, but typical actin filaments with focal densities were not found in any of the four. Other immunohistochemical markers examined including desmin, h-caldesmon and smooth muscle myosin heavy chain were negative in the tumor cells. The present results suggest that neural crest-derived tumors could show expression of alpha-smooth muscle actin on rare occasion.

Morphometry of surgically removed internal limiting membrane during vitrectomy in diabetic macular edema.

BACKGROUND: Histopathologic and morphometric analysis of the internal limiting membrane (ILM) in diabetic eyes was performed. The thickness of the ILM was correlated with the level of glycosylated hemoglobin (HbA(1C)) and other clinical factors. METHODS: The prospective study involved 56 eyes of 52 diabetic patients with a mean age of 63 +/- 7.6 years. Vitrectomy with trypan blue-assisted ILM peeling was performed in the standard way. The mean follow-up period was 8.7 months (range 3-19 months). The ILM was fixed immediately after peeling in 2.5% glutaraldehyde and submitted for electron microscopic evaluation. The ILM was photographed at standard magnification (x5,000) with the scale of 1 microm in the shot. RESULTS: Morphometric analysis demonstrated a significant thickening of the ILM in all eyes, with a mean thickness of the ILM of 3.61 +/- 1.22 microm. It was found that a higher thickness of the ILM is related to elevated HbA(1C) in both types of diabetes mellitus (DM) (p = 0.040). We also found significant dependence of ILM thickness in relation to duration of DM by comparison of men and women (p = 0.026), and a significant correlation between ILM thickness and the age of diabetic patients related to their gender (p = 0.029). CONCLUSIONS: We confirmed increased thickness of the surgically peeled ILM and statistically significant correlations to elevated HbA(1C) in both types of DM, and to further clinical characteristics of case series. Morphometric and histopathologic analyses of the ILM contribute to more objective evaluation of the ultrastructure of the vitreomacular interface.

Impact of chemotherapy on the expression of claudins and cadherins in invasive breast cancer.

The importance of the expression profile of claudins in the molecular classification of breast cancer (BC) is currently under investigation. Claudins, together with cadherins, serve an important role in the epithelial-mesenchymal transition and influence the chemosensitivity of cancer cells. Adjuvant chemotherapy is administered following surgical resection in selected cases of BC. Previous neoadjuvant chemotherapy may change the molecular profile of a tumour and subsequently also its chemosensitivity. In the current study, the expression of claudin-1, -3 and -4, E- and N-cadherin and the standard BC biomarkers [oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and marker of proliferation Ki-67 (Ki-67)] in formalin-fixed, paraffin-embedded sections from 62 patients with invasive BC was analysed using immunohistochemistry prior to and following neoadjuvant chemotherapy. The results revealed increased expression of claudin-1 (P=0.03) and decreased expression of claudin-3 (P=0.005), PR (P<0.001) and Ki-67 (P=0.01) following the neoadjuvant therapy. No significant changes in the expression of ER, claudin-4 or E- and N-cadherin were observed following therapy. Furthermore, an association between the expression of claudin-1 and the standard BC markers (P<0.05) was identified. A high expression of claudin-1 was more frequently observed in the triple-negative BC cohort than in the cohort with positive ER, PR and/or HER2 before (P=0.04) and after chemotherapy (P=0.02). The expression of N-cadherin was associated with the expression of ER, PR, HER2 and tumour grade (P<0.05). A positive association between the expression of claudin-3 and E-cadherin (P=0.005) was observed. No association was found between the expression of E- and N-cadherin. In conclusion, significant changes in the expression of claudin-1 and -3 but not in the expression of claudin-4, E- and N-cadherin were observed in samples taken from patients with BC following chemotherapy. These findings indicate that claudins-1 and -3 serve a role in the response of BC to chemotherapy.

Primary pure large-cell neuroendocrine carcinoma of the ovary.

We report a case of a 73-year-old female with a rare simultaneous occurrence of three tumors: ovarian carcinoma, endometrial carcinoma, and breast carcinoma. The ovarian tumor was a primary pure large-cell neuroendocrine carcinoma. Grossly, the left ovary was enlarged by a solid tumor that measured 9 x 7 x 7 cm. Histologically, the tumor consisted of large cells with irregular hyperchromatic nuclei and a moderate amount of eosinophilic cytoplasm. In some areas, the tumor cells were arranged in solid sheets; however, the predominant pattern was cribriform and solid-alveolar, with palisaded tumor cells located peripherally. The tumor cells showed multiple mitotic figures (up to 43 mitoses/10 HPF). Large areas of tumor necrosis were found. Immunohistochemically, the tumor cells were positive for EMA, synaptophysin, chromogranin, CD56, and CEA. Cytokeratin 20 was positive focally. Primary large-cell neuroendocrine carcinoma of the ovary is a rare tumor. To the best of our knowledge, only 4 cases of a pure tumor of this type have been reported to date.

Distribution of chondrocytes containing alpha-smooth muscle actin in human normal, osteoarthrotic, and transplanted articular cartilage.

The aim of our study was to evaluate the occurrence of chondrocytes containing alpha-smooth muscle actin in human normal and diseased cartilage. Immunohistochemistry using monoclonal antibodies for alpha-smooth actin, muscle-specific actin, S-100 protein, CD 34, and desmin was performed on samples of human articular cartilage obtained at autopsy following sudden death, during total hip and knee replacement for osteoarthritis, or after femoral neck fracture in patients without symptoms of osteoarthritis. Moreover, the layers of residual cartilage from chondral posttraumatic defects obtained during preoperative arthroscopy and of newly formed cartilage after autologous-chondrocyte transplantation (Hyalograft C) obtained during second-look arthroscopy were also examined by immunohistochemistry and RT PCR. Our study showed that a significant percentage of articular chondrocytes express alpha-smooth muscle actin in healthy, diseased, and regenerated articular cartilage. Alpha-actin positive chondrocytes (18%) were observed predominantly in the upper zone of normal articular cartilage. By contrast, only approximately 10% of cartilage cells in the deep region stained for this contractile actin isoform. Actin-positive chondrocytes (myochondrocytes) are formed predominantly in response to injury to the osteoarthrotic cartilage, at sites of defective healing, and in newly formed cartilage after autologous chondrocyte transplantation. Fibrocartilage is present in some of these conditions, and it is known that this tissue contains chondrocytes with actin. The presence of myochondrocytes in the surface layer of normal articular cartilage indicates that this region probably plays an important role in maintaining cartilage integrity. Myochondrocytes may utilize the contractile actin isoform in manipulating the extracellular matrix of articular cartilage. It is also possible that actin-containing chondrocytes have a higher potential for regeneration in contrast to chondrocytes that do not contain this contractile material in their cytoplasm.

Secondary stability assessment of titanium implants with an alkali-etched surface: a resonance frequency analysis study in beagle dogs.

PURPOSE: This study was carried out to quantify the effect of an alkali-modified surface on implant stability during healing using an animal model. MATERIALS AND METHODS: A total of 24 screw-shaped, self-tapping, commercially pure titanium dental implants, divided into a test group (implants with an alkali-modified surface or "biosurface") and a control group (implants with a turned, machined surface) were inserted without pretapping in the tibiae of 3 beagle dogs. The resonance frequency analysis method was used to measure the implant stability quotient (ISQ) 0, 1, 3, 9, and 12 weeks after implantation. The animals were sacrificed after 2, 5, and 12 weeks, and the bone-implant contact (BIC%) was evaluated histomorphometrically. RESULTS: The difference in the osseointegration rates (deltaISQ/deltahealing time) between the implants with alkali-modified surface (biosurface) and those with a turned, machined surface was evaluated as a mean of 0.843 ISQ/week within the first 9 weeks of healing. The mean increase in the secondary implant stability was found to be proportional to the mean increase in the BIC at healing period earlier than 5 weeks. DISCUSSION: The characteristics that differed between the implant surfaces, ie, specific surface area, contact angle, and hydroxylation/hydration, may represent factors that influence the rate of osseointegration and the secondary implant stability. CONCLUSION: The alkali-treated surface enhances the secondary stability in the early stages of healing compared to the turned, machined surface, as a consequence of faster BIC formation.

Rich table but short life: Diffuse idiopathic skeletal hyperostosis in Danish astronomer Tycho Brahe (1546-1601) and its possible consequences.

The exhumation of Danish astronomer Tycho Brahe (1546-1601) was performed in 2010 to verify speculative views on the cause of his death. Previous analyses of skeletal and hair remains recovered from his grave refuted the presumption that he died from poisoning. These studies also outlined the possibility that he actually died from an acute illness, echoing the rather vague and inaccurate testimony of some historical records. We performed a detailed paleopathological analysis of Tycho Brahe's skeletal remains, along with a reconstruction of his diet based on carbon and nitrogen stable isotopes analysis and an estimate of his physical status (relative body fat) based on medullar and cortical dimensions of the femoral shaft. The astronomer's remains exhibit bone changes indicative of diffuse idiopathic skeletal hyperostosis (DISH). The study further allows us to classify him as obese (100% reliability according to our decision tree designed from Danish males), and points out his rich diet (high input of animal protein and/or marine resources) and high social status. Comorbidities of DISH and obesity are reviewed, and their influence on health status is discussed. We further consider some conditions associated with metabolic syndrome as possible causes of Tycho Brahe's final symptoms (urinary retention, renal failure and coma), including diabetes, alcoholic ketoacidosis and benign prostatic hypertrophy. Although a definite and specific diagnosis cannot be established, our study points to today's civilization diseases often associated with DISH and metabolic syndrome as the possible cause of death of Tycho Brahe.

Uterine leiomyomas with inclusion bodies: an immunohistochemical and ultrastructural analysis of 12 cases.

We describe 12 cases of leiomyoma with intracytoplasmic inclusion bodies, which were detected in a group of 447 leiomyomas examined at our institution between December 2005 and March 2006. Ten of these tumors were typical leiomyomas, and two cases represented atypical (bizarre) leiomyoma. In some cases, the presence of intracytoplasmic inclusion bodies resulted in a rhabdoid or skeletal muscle-like appearance of the tumor cells. Ultrastructurally, there were two types of inclusions. One of them consisted of an abnormal aggregation of intermediate and actin filaments. Another type of inclusions was composed of dense granular material without an apparent fibrillar structure. The ultrastructure of the inclusions correlates with immunohistochemical and histochemical stainings. The inclusions with apparent fibrillar arrangements were PAS negative, stained red by trichrome, and were, at least at the periphery, actin-, desmin-, and h-caldesmon-positive. The dense granular inclusions were at least focally PAS-positive, stained red by trichrome, and were negative immunohistochemically. The intracytoplasmic inclusions were found in atypical (bizarre) leiomyomas of the uterus and occasionally in epithelioid leiomyomas and leiomyosarcomas. However, to the best of our knowledge, these inclusions have not been found in typical uterine leiomyomas to date.

Intraneural perineurioma of the oral mucosa.

A 16-year-old boy presented with an intraneural perineurioma arising from a small nerve in the buccal mucosa. Histologically, the tumour comprised a tortuous proliferation of spindle cells arranged like an onion bulb. To our knowledge this is the third example of an intraneural perineurioma that did not present in a major nerve.

Pathological findings of uterine leiomyomas and adenomyosis following uterine artery embolization.

Uterine artery embolization (UAE) is an effective and accepted treatment option for symptomatic uterine leiomyoma. Between 2000 and 2005, 91 women were treated using this method, and were prospectively followed at our institution. Twenty of them subsequently underwent surgery. One of these patients was subjected to four surgical procedures. We describe the pathological findings of 23 surgical specimens obtained from these 20 patients. The embolic material used consisted of tris-acryl gelatin microspheres (TGMS) in 15 patients (18 surgical specimens), polyvinyl alcohol particles (PVA) in three patients, and a combination of PVA and TGMS in two patients. Histologically, of the 23 specimens examined, 20 were diagnosed as leiomyomas, and three as adenomyosis. Particles used for embolization were found in all but three specimens. Necrosis was present in 15 of 20 leiomyoma specimens. Hyaline necrosis was found in 12 specimens, coagulative necrosis in one case, and a combination of hyaline and coagulative or suppurative necrosis in two cases. The foci of adenomyosis remained unaltered.

Adrenocortical adenoma with rhabdoid features.

We report a case of an aldosterone producing adrenocortical adenoma with rhabdoid features in a 16-year-old girl. Grossly, the tumor measured 30 mm in diameter and weighed 24 g. Histologically, the tumor was composed of approximately equal parts of tumor cells with rhabdoid features arranged in a solid and trabecular pattern and cells characterized by compact eosinophilic cytoplasm, solid growth with focal necroses, and increased mitotic activity. The lipid-rich tumor cells with ample clear vacuolized cytoplasm represent a minor component. Immunohistochemically, all the tumor cells showed the same results and were positive for vimentin, synaptophysin, Melan A, and alpha-inhibin. Cytokeratin CAM 5.2 was positive only focally. Chromogranin A, actin, alpha-actin, S100 protein, EMA, and cytokeratin AE1/AE3 were negative. Rhabdoid features have been described in many tumors of variable histogenesis; however, to the best of our knowledge, the presence of rhabdoid phenotype has never been described in either adrenocortical adenoma or carcinoma.

Large cell neuroendocrine carcinoma of the urinary bladder with lymphoepithelioma-like features.

The group of undifferentiated carcinomas of the urinary bladder encompasses small cell undifferentiated carcinoma, giant cell carcinoma, lymphoepithelioma-like carcinoma (LELC), and large cell neuroendocrine carcinoma (LCNEC). These tumors are either pure or can be associated with other components, such as transitional cell carcinoma, squamous cell carcinoma, and adenocarcinoma. We report a case of LCNEC of the urinary bladder in a 54-year-old woman. Histologically, the tumor showed features of LELC; immunohistochemically, the tumor cells reacted to chromogranin A, NSE, and synaptophysin. In addition to these neuroendocrine markers, tumor cells were positive for cytokeratin CAM 5.2 and AE1/AE3, and there was focal positivity for vimentin. In situ hybridization for the detection of Epstein-Barr virus was negative. Despite radical cystourethrectomy and six courses of chemotherapy, the patient developed metastases invading the left inguinal lymph nodes 11 months postoperatively. Currently, 16 months postoperatively, the patient has developed metastases spreading into the lymph nodes of the right ischiorectal fossa; therefore, she is receiving a new cyclus of chemotherapy. There are only three previously reported cases of LCNEC of the urinary bladder, and the significance of neuroendocrine differentiation in non-small cell carcinomas at this location remains to be established. However, LELC appears to be a separate clinicopathological entity with sensitivity to chemotherapy and a relatively favorable prognosis. The differentiation between LELC and LCNEC with prominent inflammatory reaction could be of therapeutic relevance. However, in our case, this was possible using immunohistochemistry only.