Search

Few studies have evaluated cytokeratin's (CK) staining patterns in atypical endometrial hyperplasia (AEH) coexisting with early-stage endometrial cancer (EC). We aimed to assess the staining patterns of selected CKs (CK7, CK19, CK20, CK AE1/AE3) in 74 patients with coexisting AEH and EC by independently analyzing both morphological variables. Specimens were collected from women with AEH and EC who underwent surgical interventions between 2012 and 2019 at the Department of Obstetrics and Gynecology of Vilnius University Hospital "Santaros Klinikos" in Vilnius, Lithuania. Immunostaining was also qualitatively classified as being heterogeneous or intense. The results revealed heterogeneous CK7 expression in all AEH cases and intense staining in 95.95% cases of AEH. The heterogeneous expression of CK7 was detected in all EC specimens. Intense CK7 expression was observed in 95.09% cases of EC G1 and in all G2 ECs. Heterogenous CK19 expression was present in all AEH specimens with intense staining in 92.42% of cases. Heterogeneous CK19 expression was observed in all EC samples with intense expression in 86.27% cases of EC G1 and 100% cases of EC G2. Interestingly, a significant relationship was found when comparing the heterogeneous expression of CK19 between AEH and well-differentiated EC. A significant difference was reported in the intense expression of CK AE1/AE3 ( p = 0.031; p = 0.029) between AEH and G2 ECs and in the intense expression of CK AE1/AE3 between G1 and G2 ECs. CK20 staining was not a characteristic feature for AEH and early-stage EC. CK staining is present either in AEH or in early-stage endometrioid-subtype EC in different manners. Heterogeneous CK19 expression was significantly more common in AEH than in EC. CK20 expression was not associated with either AEH nor early-stage EC. An intense expression of CK AE1/AE3 was mainly present in moderately differentiated ECs, whereas the intense reactivity of AE1/AE3 showed a significant difference in well to moderately differentiated uterine tumors. The clinical implication of CK staining may aid in the more accurate diagnosis of AEH and early-stage EC as well as detect micrometastases leading to better oncological outcomes.

Metaplastic thymoma is a rare biphasic thymic tumor with indolent behavior and recurrent YAP1::MAML2 gene rearrangement. Although the diagnosis of this tumor is usually straightforward based on hematoxylin and eosin (H&E) findings alone, cases with scant spindle-cell ("pseudosarcomatous stroma") components can be easily confused with more commonly occurring type A thymoma. We present a case of metaplastic thymoma with a sparse stroma-like spindle-cell component, discussing its histological and immunohistochemical hints and drawing attention to the visual similarity to type A thymoma. This is also the first published case of metaplastic thymoma with associated psoriasis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Ražanskienė et al.)

Rationale: Aberrant pancreatic tissue in the gastrointestinal tract is a relatively common finding. However, malignant transformation is extremely rare. Herein, we report a case of ectopic pancreatic ductal adenocarcinoma in the stomach wall., Patient Concerns: A 38 year old male presented with nausea, bloating, abdominal distention and weight loss for 4 months., Diagnoses: Endoscopy of upper gastrointestinal tract was performed twice with 2 months interval and a stenotic pyloric part was observed with a suspected submucosal lesion. It was sampled both times, however the pathology findings of the mucosal biopsies were unremarkable with no identifiable neoplastic structures. CT scan and MRI was performed and showed a thickened pyloric wall with a submucosal lesion 15 × 15 mm in diameter. Blood levels of tumor markers carcinoembrionic antigen and carbohydrate antigen 19-9 were within a normal range., Interventions: Pyloric stenosis progressed and the patient underwent a Billroth type I distal gastric resection with D2 lymphadenectomy. Pathologic examination revealed a well differentiated ductal adenocarcinoma arising in the heterotopic pancreatic tissue (Heinrich type III). The resection margins and lymph nodes were free of tumor. The patient received adjuvant chemotherapy with 6 courses of XELOX., Outcomes: No disease recurrence is reported in 12 months follow-up., Lessons: Aberrant pancreatic ductal adenocarcinoma in the stomach is a rare finding, however this pathology should be included in the differential diagnosis of gastric submucosal lesion causing pyloric stenosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Malignant melanoma is becoming more common among middle-aged individuals all over the world. Melanoma metastasis can be found in various organs, although metastases to the spleen and stomach are rare. Herein we present a rare metastatic multifocal melanoma, clinically and histologically mimicking lymphoma, with metastases of multiple organs., Case Summary: A 46-year-old Caucasian male with a history of nodular cutaneous malignant melanoma was presented with nausea, general weakness, shortness of breath, abdominal enlargement, and night sweating. The abdominal ultrasound revealed enlarged liver and spleen with multiple lesions. Computed tomography demonstrated multiple lesions in the lungs, liver, spleen, subcutaneous tissue, bones and a pathological lymphadenopathy of the neck. Trephine biopsy and the biopsy from the enlarged lymph node were taken. Tumor cells showed diffuse or partial positivity for melanocytic markers, such as microphthalmia - associated transcription factor, S100, HMB45 and Melan-A. The tumor harbored BRAF V600E mutation, demonstrated by immunohistochemical labelling for BRAF V600E and detected by real-time polymerase chain reaction test. Having combined all the findings, a diagnosis was made of a metastatic multifocal melanoma of the stomach, duodenum, liver, spleen, lungs, lymph nodes and bones. The patient refused treatment and died a week later., Conclusion: This case report highlights the clinical relevance of rare metastatic multifocal melanoma of multiple organ systems., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Hepatoid adenocarcinoma is an extremely aggressive special subtype of gastric tumors. It can be lethal as no standard treatment options for this type of gastric cancer exist. Here, we describe a very rare case of a young female on her 21 st week of pregnancy who was diagnosed with stage IV hepatoid adenocarcinoma of the stomach with elevated α fetoprotein (AFP) level. Gene mutation analysis performed by next-generation sequencing identified somatic mutations in the PIK3CA gene. Despite the treatment, patient died 2 months after the initial disease presentation. To our best knowledge, this case represents the first report of pregnancy-associated hepatoid gastric adenocarcinoma with the PIK3CA gene mutations, which can provide further clues for the understanding of molecular features of this type of tumor that can reflect biological behavior and may lead to further effective treatment options., (© The Author(s) 2021. Published by Oxford University Press.)

Ovarian steroid-cell tumors (SCTs) are a rare subgroup of sex-cord tumors of the ovary, accounting for less than 0.1% of all ovarian tumors. Not otherwise specified (NOS) tumors are the most common subtype. More than half of patients with SCTs-NOS show hyperandrogenic symptoms. The primary treatment for SCTs is surgery, as most cases are early-staged and benign. Because of the low incidence of metastatic disease, there is insufficient reliable information on the role of adjuvant therapy and the most effective treatment regimen. In this report, a rare case of a recurrent SCT-NOS in a 36-year-old female patient without endocrine symptoms is presented, highlighting the significance of appropriate pathological evaluation and immunohistochemical testing for the accurate diagnosis of this malignancy, particularly in the case of hormonally "silent" tumors. The metastatic tumor described here showed no response to four courses of adjuvant chemotherapy after several debulking surgeries. Based on the clinical findings, the neoplastic etiology should always be considered during the resection of ovarian tumors to prevent possible disease dissemination due to inappropriate surgical techniques.

Background: Due to ineffective ovarian cancer (OC) screening programs, prophylactic bilateral salpingo-oophorectomy (PBSO) is suggested for BRCA1/2 genes mutation carriers. The reported incidence of clinically occult neoplasia and OC detected during PBSO varies widely (2-17 %), reflecting differences in studies design., Objective: We aimed to prospectively evaluate the incidence of occult neoplasia in specimens collected during PBSO performed in a single tertiary center and to determine the effectiveness of this procedure in BRCA1/2 mutation carriers., Study Design: Between January 2010 and October 2016 a total of 564 new germline BRCA1/2 mutation positive women were identified and 71 carriers underwent laparoscopic PBSO. Patients were prospectively followed-up after the surgery and data on operation, age, complications, histological reports and BRCA1/2 gene mutation types were collected and analyzed., Results: Serous tubal intraepithelial carcinoma (STIC) was diagnosed in 7 (9.85 %) and OC in 4 (5.6 %) women (one advanced (FIGO IIIC) and 3 early (FIGO IA/C) stages); total incidence 15.5 %. Women's mean age at the time of surgery was 46.5 years. The mean age of women diagnosed with STIC and OC was 45.9 years (42-64). The mean follow up time for women being diagnosed with OC/STIC was 3.72 years; no recurrence was observed. The median time to perform laparoscopic PBSO was 43 min. (ranging from 25 to 65 min.), no surgical complications occurred during this operation. Interestingly, we found statistically significant (P = 0.0105) enrichment of STIC lesions in BRCA1 c.4035delA (an established Baltic founder mutation) carriers group., Conclusion: The incidence of pathological findings in BRCA1/2 mutation carries after PBSO is sufficiently high and our prospective study data supports PBSO as the most effective measure for reducing the risk of OC in BRCA1/2 mutation carriers. A novel finding of the enrichment of STIC lesions in BRCA1 c.4035delA carriers may show important biological differences in OC tumorigenesis between different BRCA1 mutations, which warrant further investigations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Malignant mesothelioma of the tunica vaginalis is a rare tumour which comprises less than 1% of all mesotheliomas., Case Presentation: 69-years old patient with painful hard mass and hydrocele in the right scrotum to whom a right hydrocelectomy was performed. Any history of scrotal trauma or exposure to asbestos was not present. Excisional biopsy revealed a multinodular tumour with focal areas of necrosis and infiltrative growth. According to morphological and immunohistochemical findings, diagnosis of malignant biphasic mesothelioma of the tunica vaginalis testis was made. Two months after hydrocelectomy, right inguinal orchidectomy was performed. Post-surgical whole body CT scan revealed paraaortic and pararenal lymphadenopathy, likely to be metastatic. Adjuvant treatment with 6 cycles of cisplatin and pemetrexed was applied. After 3 cycles of chemotherapy, CT scan showed progression and the treatment was changed to gemcitabine 1 month after., Conclusions: Although malignant mesothelioma of the tunica vaginalis is a rare malignancy, it poses a diagnostic challenge which can mimic common inguinal or scrotal diseases such as hydrocele. Despite aggressive surgical procedures or adjuvant therapies, the prognosis remains poor.

Diffuse pulmonary lymphangiomatosis (DPL) is a rare disease characterized by uncontrolled proliferation of anastomosing lymphatic channels in the lungs, pleura and mediastinum. Several palliative treatment options have been suggested for this condition, such as surgical interventions, radiotherapy and systemic medications. However, the existing treatment modalities yield inconsistent results, and their use is often limited by toxic side effects. The aim of this case report is to demonstrate the diagnostic challenges of a rare disease and improvement in the condition of a DPL patient treated with sirolimus. A 27-year-old man presented to the pulmonologist with exertional dyspnea, chronic cough and intermittent hemoptysis. Upon medical investigation, a chest computed tomography (CT) scan revealed soft tissue masses infiltrating the mediastinum and bilateral interlobular septal thickening. A surgical biopsy was performed, and pathological tissue analysis showed findings consistent with the diagnosis of DPL. Treatment with sirolimus was initiated, maintaining trough concentrations between 10 and 15 ng/ml. At 21 months of treatment, the patient reported reduced symptoms of cough and dyspnea. A CT scan showed decreased interstitial thickening and reduced infiltrations in the mediastinum. Moreover, pulmonary function tests revealed a significant increase in FEV1 and FVC. The authors believe this is the first article reporting pulmonary function improvement in an adult DPL patient treated with sirolimus. Therefore, sirolimus therapy should be considered for DPL patients as it may be effective in improving their condition and preventing disease progression., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article., (© 2020 The Authors. Published by Elsevier Ltd.)

Germline protein truncating variants (PTVs) in the FANCM gene have been associated with a 2-4-fold increased breast cancer risk in case-control studies conducted in different European populations. However, the distribution and the frequency of FANCM PTVs in Europe have never been investigated. In the present study, we collected the data of 114 European female breast cancer cases with FANCM PTVs ascertained in 20 centers from 13 European countries. We identified 27 different FANCM PTVs. The p.Gln1701* PTV is the most common PTV in Northern Europe with a maximum frequency in Finland and a lower relative frequency in Southern Europe. On the contrary, p.Arg1931* seems to be the most common PTV in Southern Europe. We also showed that p.Arg658*, the third most common PTV, is more frequent in Central Europe, and p.Gln498Thrfs*7 is probably a founder variant from Lithuania. Of the 23 rare or unique FANCM PTVs, 15 have not been previously reported. We provide here the initial spectrum of FANCM PTVs in European breast cancer cases., Competing Interests: The authors declare no conflict of interest.

Only 1% to 2% of meningiomas have primary extrameningeal location, which is mostly head and neck region. Primary pulmonary meningiomas (PPMs) are even more uncommon with up to 50 cases reported in the literature. Only 5 cases of PPM with confirmed or possible malignancy have been previously described. Three-grade classification of meningiomas with the accordingly growing risk of aggressive behavior of the tumor has been proposed by the World Health Organization. As it is based on correlations between morphological and clinical features of intracranial meningiomas, the analogous prediction of ectopic tumors prognosis remains questionable due to scarce number of cases. In this article, we present a rare case of PPM with rhabdoid features (World Health Organization grade III), which lacked other signs of malignancy. The patient is doing well for 2 years after the thoracoscopic wedge resection without evidence of the disease recurrence.

Background: To evaluate indications for colectomy in T1 polyps and possible risk factors for lymph node metastasis., Methods: Between 2004 and 2017, 40 patients underwent colectomy after endoscopic removal of malignant polyps with T1 carcinoma. Resection was done based on at least one of the unfavourable histopathological criteria. We collected and prospectively studied histopathologic features, short-term results and the benefit-risk balance. Complications were assessed by Clavien-Dindo classification., Results: Twenty-five patients (62.5%) underwent laparoscopic bowel resection. Twenty-nine patients (63.0%) had more than two unfavourable criteria in the polyp that justified colorectal resection. Thirty-five patients (76%) had G2 (moderately differentiated) cancer, 11 (24%) had G1 (well-differentiated). Five patients (12.5%) had lymph node metastases and one (2.5%) had residual adenocarcinoma. All five patients with lymph node metastasis had G2 cancer. Nine patients (22.5%) had residual adenoma. Overall complications were identified in six (15.0%) patients. Oncologic benefit (or risk factors for lymph node metastasis) was significantly associated with polyp size ≥18 mm (P = 0.006), lymphovascular invasion (P = 0.05) and budding (P = 0.02)., Conclusions: Female gender, lymphovascular invasion, desmoplastic reaction, criteria for surgery ≥2 and polyp size ≥18 mm were all in complex significant risk factors for lymph node metastasis in T1 colorectal cancer. Acting as a single factor, these variables had no effect to increased risk of metastasis., (© 2018 Royal Australasian College of Surgeons.)

Centrosome anomalies contribute to tumorigenesis, but it remains unclear how they are generated in lethal cancer phenotypes. Here, it is demonstrated that human microsatellite instable (MSI) and BRAF V600E -mutant colorectal cancers with a lethal rhabdoid phenotype are characterized by inactivation of centrosomal functions. A splice site mutation that causes an unbalanced dosage of rootletin (CROCC), a centrosome linker component required for centrosome cohesion and separation at the chromosome 1p36.13 locus, resulted in abnormally shaped centrosomes in rhabdoid cells from human colon tissues. Notably, deleterious deletions at 1p36.13 were recurrent in a subgroup of BRAF V600E -mutant and microsatellite stable (MSS) rhabdoid colorectal cancers, but not in classical colorectal cancer or pediatric rhabdoid tumors. Interfering with CROCC expression in near-diploid BRAF V600E -mutant/MSI colon cancer cells disrupts bipolar mitotic spindle architecture, promotes tetraploid segregation errors, resulting in a highly aggressive rhabdoid-like phenotype in vitro Restoring near-wild-type levels of CROCC in a metastatic model harboring 1p36.13 deletion results in correction of centrosome segregation errors and cell death, revealing a mechanism of tolerance to mitotic errors and tetraploidization promoted by deleterious 1p36.13 loss. Accordingly, cancer cells lacking 1p36.13 display far greater sensitivity to centrosome spindle pole stabilizing agents in vitro These data shed light on a previously unknown link between centrosome cohesion defects and lethal cancer phenotypes providing new insight into pathways underlying genome instability. Implications: Mis-segregation of chromosomes is a prominent feature of chromosome instability and intratumoral heterogeneity recurrent in metastatic tumors for which the molecular basis is unknown. This study provides insight into the mechanism by which defects in rootletin, a centrosome linker component causes tetraploid segregation errors and phenotypic transition to a clinically devastating form of malignant rhabdoid tumor. Mol Cancer Res; 16(9); 1385-95. ©2018 AACR ., (©2018 American Association for Cancer Research.)

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations., (© 2018 Wiley Periodicals, Inc.)

Background: MiRNAs are often deregulated in colorectal cancer and might function as tumor suppressors or as oncogenes. They participate in controlling key signaling pathways involved in proliferation, invasion and apoptosis and may serve as prognostic and predictive markers. In this study we aimed to evaluate the role of miRNA-148a and miRNA-625-3p in metastatic colorectal cancer., Methods: Fifty-four patients with a first-time diagnosed CRC receiving FOLFOX ± Bevacizumab were involved in the study. Tumor samples underwent routine pathology examination including evaluation for tumor budding and KRAS. MiRNA-148a and miRNA-625-3p expression analysis was done by RT-PCR. Associations between expression of both miRNAs and clinico-pathological factors, treatment outcomes and survival were analyzed., Results: Both miRNA-148a and miRNA-625-3p were down-regulated in the tumors compared to normal colonic mucosa. Significantly lower expression of both miRNAs was noticed in tumors with budding phenomenon compared to tumors without it (median values of miRNA-148a were 0.314 and 0.753 respectively, p = 0.011, and 0.404 and 0.620 respectively for miRNA-625-3p, p = 0.036). Significantly lower expression of miRNA-625-3p was detected in rectal tumors, compared to tumors in the colon (median 0.390 and 0.665 respectively, p = 0.037). Progression free survival was significantly lower in patients with high miRNA-148a expression (6 and 9 months respectively, p = 0.033), but there were no significant differences in PFS for miRNA-625-3p and in overall survival for both miRNAs., Conclusions: There was a significant relationship between low miRNA-148a and miRNA-625-3p expression and tumor budding, which is thought to represent epithelial-mesenchymal transition. Both studied miRNAs may be associated with a more aggressive phenotype and could be the potential prognostic and predictive biomarkers in CRC. Further investigation is needed to confirm miRNAs involvement in EMT, and their prognostic and predictive value.

Background. KRAS mutation is an important predictive and prognostic factor for patients receiving anti-EGFR therapy. An expanded KRAS, NRAS, BRAF, PIK3CA mutation analysis provides additional prognostic information, but its role in predicting bevacizumab efficacy is unclear. The aim of our study was to evaluate the incidence of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer patients receiving first line oxaliplatin based chemotherapy with or without bevacizumab and to evaluate their prognostic and predictive significance. Methods. 55 patients with the first-time diagnosed CRC receiving FOLFOX ± bevacizumab were involved in the study. Tumour blocks were tested for KRAS mutations in exons 2, 3 and 4, NRAS mutations in exons 2, 3 and 4, BRAF mutation in exon 15 and PIK3CA mutations in exons 9 and 20. The association between mutations and clinico-pathological factors, treatment outcomes and survival was analyzed. Results. KRAS mutations were detected in 67.3% of the patients, BRAF in 1.8%, PIK3CA in 5.5% and there were no NRAS mutations. A significant association between the high CA 19-9 level and KRAS mutation was detected (mean CA 19-9 levels were 276 and 87 kIU/l, respectively, p = 0.019). There was a significantly higher response rate in the KRAS, NRAS, BRAF and PIK3CA wild type cohort receiving bevacizumab compared to any gene mutant type (100 and 60%, respectively, p = 0.030). The univariate Cox regression analysis did not confirm KRAS and other tested mutations as prognostic factors for PFS or OS. Conclusions. Our study revealed higher KRAS and lower NRAS, BRAF and PIK3CA mutation rates in the Lithuanian population than those reported in the literature. KRAS mutation was associated with the high CA 19-9 level and mucinous histology type, but did not show any predictive or prognostic significance. The expanded KRAS, NRAS, BRAF and PIK3CA mutation analysis provided additional significant predictive information.

Background: Yolk sac tumour diagnosis should be considered for young age patients admitted to the hospital with non-specific complaints of widespread disease. Correct diagnosis and carefully planned treatment is the key to a successful outcome., Methods and Materials: We present a rare case of a widespread yolk sack tumour of a uterine broad ligament. Our team directed a special attention towards the patient's young age, advanced disease, and fertility sparing strategy of treatment., Results and Conclusions: Stage IV yolk sac tumours of extragonadal origin are rarely reported in the literature. Hence, diagnosis and treatment often pose a challenge for emergency care unit doctors, gynaecologists, and oncologists. However, it can be a potentially curable disease. Moreover, patients' fertility can also be preserved. We believe that further analysis of similar cases is necessary to study outcomes and evaluate patients' responses to a sequence of medical decisions taken for this specific case.

Aims: Primary effusion lymphoma (PEL) is a rare form of aggressive B-cell lymphoma, which typically manifests as malignant effusion in the body cavities. However, extracavitary solid variants are also described. The aim of this study was to investigate copy number aberrations in two cases of solid PEL at their first occurrences and relapse by applying a newly developed methodology of tumour nuclei enrichment., Methods and Results: Using histological and genetic techniques, a novel protocol for tumour nuclei enrichment by flow sorting and array-comparative genomic hybridization, we characterized two cases of extracavitary PEL, one of which later relapsed as effusion. Both primary tumours were positive for HHV8 and EBV, confined to lymph nodes, and aberrantly expressed CD3, yet displaying clonal immunoglobulin gene rearrangements indicating B-cell origin. Cytogenetic characterization of primary tumours revealed modest number of aberrations, partially overlapping with previously reported affected loci. The effusional relapse in case 1 was cytogenetically related to the primary tumour but showed dramatic increase of chromosomal instability., Conclusions: We for the first time demonstrate a cytogenetic relationship between solid and effusional presentations of PEL. Moreover, we provide an indirect evidence of multiple malignant clones, which gave rise to clonally-related, yet karyotypically different relapsing lymphoma manifestations., (© 2014 John Wiley & Sons Ltd.)

There is limited knowledge about the BRCA1/2 mutational profile in Lithuania. We aimed to define the full BRCA1 and BRCA2 mutational spectrum and the clinically relevant prevalence of these gene mutations in Lithuania. A data set of 753 unrelated probands, recruited through a clinical setting, was used and consisted of 380 female breast cancer cases, 213 epithelial ovarian cancer cases, 20 breast and ovarian cancer cases, and 140 probands with positive family history of breast or ovarian cancer. A comprehensive mutation analysis of the BRCA1/2 genes by high resolution melting analysis coupled with Sanger sequencing and multiplex ligation-dependent probe amplification analysis was performed. Genetic analysis revealed 32 different pathogenic germline BRCA1/2 mutations: 20 in the BRCA1 gene and 12 in the BRCA2 gene, including four different large genomic rearrangements in the BRCA1 gene. In all, 10 novel BRCA1/2 mutations were found. Nine different recurrent BRCA1 mutations and two recurrent BRCA2 mutations were identified, which comprised 90.4% of all BRCA1/2 mutations. BRCA1 exon 1-3 deletion and BRCA2 c.658_659del are reported for the first time as recurrent mutations, pointing to a possible Baltic founder effect. Approximately 7% of breast cancer and 22% of ovarian cancer patients without family history and an estimated 0.5-0.6% of all Lithuanian women were found to be carriers of mutations in the BRCA1 or BRCA2 gene., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Until recently, hematopoietic neoplasms were considered monoclonal proliferations belonging to one cell lineage. In the last years, evidence for transdifferentiation from one cell lineage to another or divergent common progenitor cell differentiation has accumulated, mainly based on composite hematolymphoid tumors, sharing common genetic abnormalities. We report the case of a 59-year-old woman with a composite pro-T lymphoblastic lymphoma (LBL) and indeterminate dendritic cell tumor infiltrating the lymph nodes, bone marrow and stomach. Genetic analyses revealed that both cell populations bore +21, while a G13D mutation of the NRAS gene and monosomy 18 were detected only in the pro-T LBL. The synchronous appearance of two distinct uncommon hematolymphoid tumors in the same patient, recurrent at three different anatomic locations, with an identifiable common genetic denominator, namely +21, but also with unique genetic anomalies in the pro-T LBL raises the hypothesis of a divergent common progenitor cell differentiation.

Rhabdoid colonic tumors are very rare lesions with just a few publications describing such neoplasms. Even more unusual for these lesions are their primary rectal locations, with only two brief case reports having been published on that subject to date. We present a case of a composite rhabdoid rectal carcinoma in a 49-year-old male. The tumor behaved very aggressively, with rapid patient demise despite radical surgery and intensive postoperative chemotherapy (FOLFIRI [folinic acid {leucovorin}, fluorouracil {5-fluorouracil}, and irinotecan] and FOLFOX4 [folinic acid {leucovorin}, fluorouraci {5-fluorouracil}, and oxaliplatin]). Pathologic examination was supportive of a rhabdoid carcinoma, with a compatible immunohistochemical profile, demonstrating synchronous expression of vimentin and epithelial markers in the tumor cells. In addition, BRAF V600E gene mutation, together with a wild-type KRAS gene, was identified, and no evidence of microsatellite instability based on MLH1, MSH2, MSH6, and PMS2 immunophenotypes, i.e., no loss of expression for all 4 markers, was observed. Our reported case confirms previously published observations of the clinical aggressiveness and the poor therapeutic response for rhabdoid tumors.

A 14-year-old boy presented with asymptomatic right hydronephrosis detected on routine yearly ultrasound examination. Previously, he had at least two normal renal ultrasonograms, 4 years after remission of acute myeloblastic leukemia, treated by AML-BFM-93 protocol. A function of the right kidney and no damage on the left was confirmed by a DMSA scan. Right retroperitoneoscopic nephrectomy revealed 3 renal arteries with the lower pole artery lying on the pelviureteric junction. Histologically chronic tubulointerstitial nephritis was detected. In the pathogenesis of this severe unilateral renal damage, we suspect the exacerbation of deleterious effects of cytostatic therapy on kidneys with intermittent hydronephrosis.

Germline TP53 gene mutations are associated with complex cancer predisposition syndrome, the Li--Fraumeni syndrome, and are not as rare as were previously thought. Currently, the identification of Li--Fraumeni syndrome is mostly based on a conformance to descriptive criteria, which recently were amended to include wider spectrum of malignancies. The presence of very young age-onset breast cancers in TP53 mutations families is a feature that overlaps with hereditary breast/ovarian cancer families with BRCA1/2 genes mutations. Peri-diagnostic germline TP53 testing results in breast cancer patients can significantly affect surgical and adjuvant radiotherapy choices. The aim of this case report is to emphasize the importance of peri-diagnostic germline TP53 molecular testing in patients with early-onset breast cancer and its effect on the management and outcome of the disease. We present the apparent BRCA1-related, although mutation negative, breast and ovarian cancer patient who subsequently was confirmed to be TP53 c.817C>T (p.R273C) mutation carrier and discuss the importance of peri-diagnostic oncogenetic TP53 testing in early breast cancer cases. Histopathology and genetic modifiers (MDM2 SNP309G; TP53 R72P, PIN3) data are also addressed., (© 2011 Wiley Periodicals, Inc.)

Systemic mastocytosis is an uncommon condition characterized by abnormal proliferation of mast cells in one or more organ. The specific D816V KIT mutation is present in most cases. Gastrointestinal symptoms occur commonly but histologic characterization of gastrointestinal involvement is incomplete. The purpose of this study was (1) to describe the clinicopathologic features in five patients with systemic mastocytosis involving the gastrointestinal tract and (2) to determine whether gastrointestinal involvement is associated with the usual D816V mutation or a different mutation. Clinical details were obtained from the hospital of origin or referring pathologist. Histologic features were documented in slides stained with hematoxylin and eosin, mast cell tryptase and CD117. Molecular analysis for the D816V KIT mutation was performed on formalin-fixed paraffin-embedded sections. Symptoms included diarrhea/loose stools (n=5), abdominal pain (n=4), vomiting (n=3) and weight loss (n=3). Other findings included cutaneous lesions of mastocytosis (n=4), malabsorption (n=2), hypoalbuminemia (n=2) and constitutional growth delay (n=1). Sites of gastrointestinal involvement included the colon (n=5), duodenum (n=3) and terminal ileum (n=3). Endoscopic/gross findings included mucosal nodularity (n=4), erosions (n=2) and loss of mucosal folds (n=2). In three patients the endoscopic appearance was considered consistent with inflammatory bowel disease. All cases showed increased mast cell infiltration of the lamina propria, confirmed by immunohistochemistry for mast cell tryptase and CD117. In two cases, mast cells had abundant clear cytoplasmic resembling histiocytes. Marked eosinophil infiltrates were present in four patients, in one patient leading to confusion with eosinophilic colitis. Architectural distortion was noted in three cases. The D816V KIT mutation was present in all four cases tested. In conclusion, gastrointestinal involvement by systemic mastocytosis is characterized by a spectrum of morphologic features that can be mistaken for inflammatory bowel disease, eosinophilic colitis or histiocytic infiltrates. Systemic mastocytosis involving the gastrointestinal tract is associated with the usual D816V KIT mutation.

This article contains histological review of prostate biopsies techniques from the digitally guided prostate biopsies to modern extended-core prostate biopsy protocols. The technique of transrectal ultrasonography (TRUS) guided biopsy of the prostate has evolved considerably since the original description by K. K. Hodge and colleagues. A better understanding of the zonal anatomy of the prostate coupled with 3-D mapping of tumors in early stage prostate cancer has led to more laterally-directed biopsies and an increase in the number of cores obtained in a single setting. Most investigators recommend sampling between 10 and 12 areas, with particular focus on the lateral segments of the gland. Data gained from systematic extended-core biopsy protocols offer the hope of providing both diagnostic and prognostic information and may help urologists and patients make better informed decisions when facing with the diagnosis of prostate cancer. The first TRUS-guided sextant biopsy in Lithuania was performed at the Department of Urology, Institute Oncology of Vilnius University in 2000. Today the techniques used for TRUS-guided biopsies have evolved and now a protocol as a standard for an initial biopsy recommends obtaining 10 to 12 cores extended to lateral pattern.