Tumors In Young Patients Research Articles

COX2 expression is associated with preoperative tumor volume but not with volumetric tumor growth in vestibular schwannoma

ObjectiveVestibular schwannomas (VS) are benign slow growing tumors arising from the vestibular nerve. The role of cyclooxygenase 2 (COX2) in tumor development of growth has been addressed in a few studies with contradictory results and suggestions. We recently analyzed the immunohistochemical expression of COX2 in 1044 VS samples and described an association of higher COX2 expression with proliferation but found no influence by regular intake of acetylsalicylic acid. We now collected volumetric radiographic data of the preoperative tumor volume and growth to further test the role of COX2 in VS growth.MethodsPreoperative images of 898 primary sporadic vestibular schwannomas were assessed, and sufficient preoperative imaging was used for the volumetric measurement preoperative tumor volume (n = 747) and preoperative relative tumor growth (n = 171). Clinical parameters and results of the immunohistochemical expression of COX2 and MIB1 in resected tumor tissue samples were obtained from our prior study. ANOVA, CART-analysis and multivariate nominal logistic regression were used for statistical analysis.ResultsLarger preoperative tumor volumes were observed with tumors of younger patients (p = 0.0288) and with higher COX2 expression scores (p < 0.0001). Higher MIB1 expression was associated with smaller tumors (p = 0.0149) but with increased radiographic tumor growth (p = 0.0003). Patients of older age had tumors with slower growth rates (p = 0.0311). In the multivariate analysis only MIB1 expression was an independent significant factor regarding tumor growth (p = 0.0002).ConclusionsHigher expression of COX2 in schwannoma is associated with an increased preoperative tumor volume but not with radiographic tumor growth over time.

Abstract PS7-74: Associations and spectrum of genetic mutations in younger patients with breast carcinoma and additional malignancies

Abstract Background: The development of cancer is understood to be a series of molecular events causing uncontrollable cell growth and malignant behavior. Primary breast carcinoma is associated with a number of molecular alterations that may also be implicated in the molecular deregulation underlying other malignancies. In addition, underlying germline genetic mutations have been clearly associated with the development of breast carcinoma (BC) in young patients. Increased risks for the development of additional malignancies following or preceding breast cancer have been reported, however, specific associations and genetic mutations remain unclear, especially in young patients.Materials and methods: Our patient cohort consisted of young women (&amp;lt;!–=40 years of age) at our institution who were diagnosed with BC between May 2009 to May 2018. Retrospective review of electronic medical records was performed in order to identify the occurrence of a second neoplasm either before or after a BC diagnosis and germline genetic alterations were recorded.Results: 13 out of 437 young women were diagnosed with either a second malignancy or high-grade dysplasia. The clinico-pathologic characteristics of these patients are summarized in the Table 1. There was almost an equal distribution of these neoplasms occurring either before or after the diagnosis of BC. 6 tumors were diagnosed 10 months to 7 years after the diagnosis of BC, whereas 5 tumors diagnosed 1 month to 20 years earlier. Interestingly, only 2 cases were concurrently diagnosed and both of these were malignant phyllodes tumors of the breast.On studying the pathologic characteristics of the breast tumors in young patients with a second malignancy, the majority of these cancers were either grade 1 or grade 2 (10/13) while 3/13 were grade 3 carcinomas. Additionally, 10/13 of the cases were positive for estrogen receptor and negative for HER2, 2 cases were triple negative, and hormone receptor status was unknown in one case. 10/13 carcinomas were treated with mastectomy and the remaining 3 by lumpectomy. Lymph nodes were examined in 9 cases and one or more lymph nodes were found to be positive in 3 cases. Germline mutations panel (limited or complete) were available in 12 cases. Germline genetic alterations were found in three of the patients (3/12), as summarized in the Table 1. These included BRCA1 (2/12) and PTEN (1/12). Although variant of uncertain significance (VUS) mutations were also recognized in other genes e.g. ATM (1/12), SMAD4 (1/12) and MSH2 (1/12), those were not included in our analysis due to lack of current knowledge regarding their clinical significance.Additionally, 51 benign neoplasms were also diagnosed (e.g. benign nevi, thyroid adenomas, benign ovarian neoplasms, etc.). Nearly half (20/51) involved the female genital tract (uterus, cervix, or ovaries), 17 the skin and soft tissues, 4 the gastrointestinal tract, 8 the thyroid, and 1 the brain.Conclusions: Young women with BC are likely to have an underlying genetic predisposition for the development of BC and other malignancies. Although BRCA1 was the most common mutation observed, germline mutations of other genes were also seen. Therefore, genetic counselling, testing, and increased surveillance are extremely useful tools in managing the development of other associated malignancies in young women with BC. Table 1: Summary of clinico-pathologic characteristics of BC with second malignanciesNo.Type of carcinomaGradePrognostic markersAssociated in-situ carcinomaAge at diagnosisSecondary diagnosisTimeline of second diagnosisInitial management of BCLymph node statusGenetic testing results1.Invasive lobular carcinoma1UnknownLobular carcinoma in situ39Malignant phyllodes tumorConcurrentMastectomyNegativeUnknown2.Invasive ductal carcinoma3Triple negativeDuctal carcinoma in situ36Squamous cell carcinoma, esophagus7 years laterMastectomyNegativeBRCA1+3.Invasive ductal carcinoma3Triple negativeNone38High grade serous carcinoma, ovary5 years laterMastectomyOne lymph node positiveBRCA1+4.Invasive ductal carcinoma with mucinous features1Estrogen receptor+/Progesterone receptor+/HER2-Ductal carcinoma in situ33Gastrointestinal stromal tumor, jejunum7 years laterMastectomyNegativeNegative5.Invasive ductal carcinoma2Estrogen receptor+/Progesterone receptor+/HER2-Lobular carcinoma in situ31Malignant phyllodes tumor7 years earlierMastectomyNegativeNegative6.Invasive ductal carcinoma2Estrogen receptor+/Progesterone receptor-/HER2-Ductal carcinoma in situ37Complex endometrial hyperplasia with atypia and leiomyoma with Fumarate hydratase features6 years laterMastectomyNot performedNegative7.Invasive ductal carcinoma2Estrogen receptor+/Progesterone receptor+/HER2-None36Hodgkin disease20 years earlierMastectomyNegativeNegative8.Invasive ductal carcinoma3Estrogen receptor+/Progesterone receptor+/HER2-Ductal carcinoma in situ29High grade squamous intraepithelial lesion1 year earlierMastectomyOne lymph node positiveNegative9.Invasive ductal carcinoma2Estrogen receptor+/Progesterone receptor+/HER2-Ductal carcinoma in situ36High grade squamous intraepithelial lesion1.5 year laterMastectomyOne lymph node positiveNegative10.Invasive ductal carcinoma2Estrogen receptor+/Progesterone receptor+/HER2-Ductal carcinoma in situ36High grade squamous intraepithelial lesion1 month earlierLumpectomyNegativeNegative11.Invasive ductal carcinoma1Estrogen receptor+/Progesterone receptor+/HER2-Ductal carcinoma in situ38Endometrioid adenocarcinoma10 months laterLumpectomyNot performedCowden syndrome (PTEN gene)12.Invasive mucinous carcinoma1Estrogen receptor+/Progesterone receptor+/HER2-Ductal carcinoma in situ41Papillary thyroid carcinoma14 years earlierLumpectomyNot performedNegative13.Invasive tubular carcinoma1Estrogen receptor+/Progesterone receptor+/HER2-Ductal carcinoma in situ37Malignant phyllodes tumorConcurrentMastectomyNegativeNegative Citation Format: Indu Agarwal, Brian Finkelman, Luis Z. Blanco, Amir Behdad, Kalliopi Siziopikou. Associations and spectrum of genetic mutations in younger patients with breast carcinoma and additional malignancies [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-74.

The association between the histopathological features and microsatellite instability in young patients with urothelial carcinoma of the bladder.

Bladder cancer under the age of 40 is extremely rare. Bladder cancer development involves complex and multi-stage processes, one of which is the DNA damage repair mechanism. In this retrospective study, we aimed to evaluate the histopathological features of bladder urothelial carcinoma seen in patients under 40 years of age and tumor microsatellite instability status using immunohistochemistry. A total of 50 patients under the age of 40 with urothelial bladder carcinoma from two different centers in the same country were included. Expression of the mismatch repair proteins MLH1, MSH2, MSH6, and PMS2 was analyzed by immunohistochemistry. Age at the time of diagnosis ranged from 17 to 40 years old. Most tumors were non-invasive papillary urothelial carcinoma. Two cases had nuclear loss of MSH-6 and PMS-2. We observed that tumor grade, tumor stage, presence of tumor differentiation, and infiltrative growth pattern of the tumor have significant impact on prognosis, but microsatellite instability does not have an effective role in bladder carcinogenesis in young patients. Our results indicate that the presence of microsatellite instability is not related to the low tumor grade and stage in urothelial neoplasms in young patients, suggesting that urothelial carcinoma of the bladder in young patients may represent a genetically stable form of neoplasia.

An atypical teratoid/rhabdoid tumor (AT/RT) with molecular features of pleomorphic xanthoastrocytoma (PXA) in a 62-year-old patient.

Atypical teratoid/rhabdoid tumors (AT/RT) are aggressively growing malignant embryonal neoplasms of the central nervous system (CNS), which mainly affect young children. Loss of SMARCB1/INI1 (or SMARCA4 in rare cases) is recognized as the genetic hallmark of AT/RTs and these tumors can be distinguished into three distinct DNA-methylation based molecular subgroups (i.e. -MYC, -SHH and -TYR). While most AT/RTs are considered to occur de novo, previous studies have recognized secondary SMARCB1/INI1-deficient rhabdoid tumors arising from other low grade CNS tumors in young patients. Three AT/RTs, which harbor epigenetic and mutational characteristics of pleomorphic xanthoastrocytoma (PXA), while being entirely void of nuclear SMARCB1/INI1 expression, were recently described in older children. We here report the first case of an AT/RT with molecular features of PXA in a senior patient.

Fibrolamellar liver cancer: the modern concept

Fibrolamellar hepatocellular carcinoma (FLC) is a relatively rare primary liver tumor of unknown etiology (chronic infections with hepatitis B or C viruses, chronic alcohol poisoning, cirrhosis of the liver), which occurs mainly in the young population. FLK is more often diagnosed already at common stages due to the absence of pronounced clinical manifestations in patients for a long time. In pathomorphological diagnostics, FLC is a cluster of large polygonal eosinophilic cells with a clearly defined vesicular nucleus, surrounded by abundant growths of lamellar fibrosis. In most cases, collagen fibers are arranged in parallel strands; in metastatic tumors, collagen fibers can be arranged haphazardly (the so-called “tangled fibers”).For many years, attempts have been made to identify reliable markers for the detection and differential diagnosis of FLC and to determine the cause of tumors in young patients, and the molecular mechanisms of FLC carcinogenesis have been studied. In 2014 during the full transcriptome analysis of FLC samples, the chimeric transcript DNAJB1PRKACA was discovered, which is formed as a result of deletion of a section of chromosome 19 with a size of 400 thousand nucleotide pairs and leads to the fusion of two genes, which Is found in most FLC samples. Surgery is the only curative treatment of this tumor type and radical method of treating the disease. Given that lymph node involvement is an important prognostic factor, complete periportal lymphadenectomy should be performed as part of radical surgery for patients with FLK. The role and possibilities of locoregional and drug-based treatment methods are not fully clear, and the search for effective treatment regimens and potential targets specific to this form of HCR is urgent. Studies show conflicting results for different chemotherapy regimens and the use of targeted therapy. The literature describes isolated clinical cases of successful use of immunotherapy in patients with PD-L1-expressing tumors. The most important condition for successful treatment is an in-depth study of the molecular mechanisms of FLC carcinogenesis. This review presents current data on epidemiology, classification, clinico-morphological, molecular and genetic aspects, as well as some diagnostic features and FLC treatment modalities.

Octogenarians present with a less aggressive phenotype of colon adenocarcinoma

BackgroundOctogenarians constitute a growing percentage of patients diagnosed with colon malignancies. This study aims to determine if the clinical and pathologic presentation of octogenarians with colon cancer differs from that of patients diagnosed at a younger age. MethodsData were collected retrospectively for all patients diagnosed with colon cancer who underwent resection at a single institution between January 1, 2004 and December 31, 2017; patients with rectal cancer were excluded. Patients were categorized by age at diagnosis: either 50 to 79 years of age or ≥80 years of age; those <50 years of age were excluded because of the greater risk of a hereditary etiology. The primary outcome was the correlation between patient age and pathologic features of the tumor, including tumor size, lymph node metastases, perineural invasion, and extramural venous invasion. ResultsOf 1,301 patients, 329 (25%) were ≥80. Female patients predominated the octogenarian cohort (61% vs 39%; P < .001). Octogenarians presented with larger tumors when compared to patients age 50 to 79 (5.2 cm vs 4.5 cm; P < .001). More patients ≥80 had tumors which were >8 cm (17.3% vs 8.9%; P < .001). Tumors in younger patients were more often detected on screening colonoscopy (23.1% vs 7.3%; P < .001). Regardless of tumor size, octogenarians were less likely to have positive lymph nodes than younger patients (P = .02). In addition, octogenarians were less likely to exhibit extramural venous invasion compared to younger patients across all tumor sizes (P < .001). Younger patients had greater median overall survival (6.4 years vs 4.4 years; P < .001), yet 3-year disease-free survival was comparable between age groups (P = .12). ConclusionOctogenarians with colon cancer present with larger tumors but appear to have less aggressive disease, as reflected in a lower pathologic stage, less extramural venous invasion, and less lymph node metastases, than younger patients with similar size tumors. Three-year disease-free survival is comparable between octogenarians and patients aged 50 to 79.

Computed tomography of the head and the risk of brain tumours during childhood and adolescence: results from a case–control study in Japan

To clarify whether medical radiation exposure, especially from head computed tomography (CT), increases the risk of brain tumours in young patients in Japan, which ranks the second highest in the world in the number of paediatric CT examinations following the US. From 2011 to 2015, we performed a case–control study of 120 brain tumour patients and 360 appendicitis patients as controls. Reasons, the number of brain and head CT scans date were available from interviews. A cumulative radiation dose to the brain was calculated as a sum of doses received from head CT scans and from conventional x-rays and estimated using a reference table derived from a literature review of published studies. We performed conditional logistic regression to assess the risk of brain tumours from brain and head CT, and from conventional head x-ray procedures. The case group received on average 1.8 CTs to the brain area and 2.2 CTs to the whole head, with a mean estimated brain dose of 32 ± 13 mGy. The odds ratio for developing a brain tumour from having a brain CT was 0.93 (95% confidence interval: 0.38–1.82). This was hardly altered when adjusting for parental educational history and for other diseases (history of neurological disease and attention-deficit disorder/attention-deficit hyperactivity disorder). Neither whole head CT nor cumulative brain dose to the brain increased the risk of glioma or of all brain tumours. Although this study conducted in Japan, where ranks second in the number of CT scans conducted in the world, did not show an increased risk of brain tumours related to CT scans, it should be taken with caution due to a case–control study with limited sample size.

Novel aspects on gonadotoxicity and fertility preservation in lymphoproliferative neoplasms.

The topic of fertility preservation in patients with a lymphoproliferative disease offers new aspects of debate, due to the introduction of novel chemotherapeutic regimens and small molecules in the clinical landscape. Cancer related infertility is mostly dependent on gonadotoxic treatments and fertile female patients are today addressed to the oocyte cryopreservation or to ovarian cortex fragment cryopreservation. These methods present advantages and disadvantages, which will be discussed in the present review, together with the options for male patients. The recent discovery of functional ovarian stem cells (OCSs) in woman ovarian cortex, opens new avenues offering a innovative procedure for fertility preservation through as model of regenerative medicine. Here, we review the gonadotoxic potential of "classical" chemotherapeutic treatments as well as of "novel" targeted therapies actually employed for lymphoproliferative neoplasms in young patients and revisit both the today available and future chances to preserve and restore fertility after the cancer healing.

Clinicopathological characterisation of renal cell carcinoma in young adults: a contemporary update and review of literature.

Renal cell carcinomas are relatively rare in children and young adults. While well characterised in adults, the morphological and molecular characterisation of these tumours in young patients is relatively lacking. The objective of this study was to explore the spectrum of renal cell carcinoma (RCC) subtypes in children and young adults and to determine their clinico-pathological, immunohistochemical and molecular characteristics by evaluating a large retrospective cohort of renal cell carcinoma patients age 30years or younger. Sixty-eight cases with confirmed diagnosis of renal cell carcinoma at age 30years or younger were identified at our institution. Clear cell carcinoma accounted for the most common subtype seen in this age group. Translocation renal cell carcinoma and rare familial syndrome subtypes such as succinate dehydrogenase deficient renal cell carcinoma and tuberous sclerosis complex-associated renal cell carcinoma were found relatively more frequently in this cohort. Despite applying the 2016 WHO classification criteria, a high proportion of the tumours in our series remained unclassified. Our results suggest that renal cell carcinoma in children and young adults is a relatively rare disease that shares many histological similarities to renal cell carcinoma occurring in adults and yet demonstrate some unique clinical-pathological differences. Microphthalmia-associated transcription (MiT) family translocation RCC and rare familial syndrome subtypes are relatively more frequent in the paediatric and adolescent age groups than in adults. Clear cell RCC still accounted for the most common subtype seen in this age group. MiT family translocation RCC patients presented with advanced stage disease and had poor clinical outcomes. The large and heterogeneous subgroup of unclassified renal cell carcinoma contains phenotypically distinct tumours with further potential for future subcategories in the renal cell carcinoma classification.

Hemangiopericytomas: Spatial Intracranial Location in a Voxel-Based Mapping Study.

To investigate the preferred location of intracranial hemangiopericytomas (IHPCs) with voxel-based mapping and 3-dimensional reconstruction from MRI data. Gadolinium-enhanced tumors of 258 primary and single IHPCs were segmented semi-automatically, followed by manual checking and editing of boundaries. The lesions were registered to Montreal Neurological Institute standard anatomical space, and heat-map and 3-dimensional rendered frequency images were generated. All tumors were then superimposed on the Anatomical Automatic Labeling (AAL) template to further investigate the difference in the tumor location based on the voxel-wise frequency of occurrence with respect to laterality, sex, age, and pathologic grade. The 3-dimensional rendered images show that the tumors commonly located in the posterior cranial cavity, surrounding the tentorium. The posterior third of the superior sagittal sinus and the confluence of sinuses were commonly affected. According to the analysis of tumor occurrence frequency in the AAL template, IHPCs were mainly observed in the limbic lobe, occipital lobe, and cerebellum. Tumors in younger patients preferentially located in the right occipital region (P = .027), whereas those with higher pathological grade more often located in the left parietal lobe (P = .034). This is the first voxel-based study to explore the predilection site of IHPCs. Our study suggests that these tumors commonly affect the posterior cranial cavity, adjoining the tentorium and venous sinus. Further research is needed to investigate the possible factors underlying these topographic preferences.

Growth Rates of Genetically Defined Renal Tumors: Implications for Active Surveillance and Intervention.

Published series of growth rates of renal tumors on active surveillance largely consist of tumors without pathologic or genetic data. Growth kinetics of genetically defined renal tumors are not well known. Here, we evaluate the growth of genetically defined renal tumors and their association with patient clinical and genetic characteristics. We evaluated patients with an inherited kidney cancer susceptibility syndrome as a result of a pathologic germline alteration of VHL, MET, FLCN, or BAP1 with at least 1 solid renal mass managed with active surveillance at our institution. Tumor growth rates (GR) were calculated and patients were stratified by genetic alteration and other clinical and genetic factors to analyze differences in growth rates using linear regression and comparative statistics. A total of 292 patients with 435 genetically defined tumors were identified, including 286 VHL-deficient, 91 FLCN-deficient, 52 MET-activated, and 6 BAP1-deficient tumors. There were significant differences in GRs when stratified by genetic alteration. BAP1-deficient tumors had the fastest median GR (0.6 cm/y; interquartile range [IQR], 0.57-0.68 cm/y), followed by VHL-deficient tumors (GR, 0.37 cm/y; IQR, 0.25-0.57 cm/y), FLCN-deficient tumors (GR, 0.10 cm/y; IQR, 0.04-0.24 cm/y), and tumors with MET activation (GR, 0.15 cm/y; IQR, 0.053-0.32 cm/y; P < .001). Tumors from the same patient had similar GRs. Younger age was independently associated with higher GR (P = .005). In a cohort of genetically defined tumors, tumor growth rates varied in a clinically and statistically different manner according to genetic subtype. Rapid growth of BAP1-deficient tumors indicates that these patients should be managed with caution. The faster growth of tumors in younger patients may support more frequent imaging, whereas the slower growth of other tumors may support extended surveillance beyond annual imaging in some instances.

A randomized trial of stereotactic versus conventional radiotherapy in young patients with low-grade brain tumors: occupational therapy-based neurocognitive data.

BackgroundRadiotherapy for brain tumors in young patients is not only associated with improved survival but also long-term neurocognitive sequelae. We aimed to compare group differences in the executive neurocognitive outcomes in young patients with low-grade brain tumors treated with stereotactic conformal radiotherapy (SCRT) and conventional RT (ConvRT) techniques.MethodsThis a phase 3 randomized trial that enrolled 200 young patients with benign brain tumors and low-grade gliomas. Patients were randomly allocated (1:1) to either SCRT or ConvRT arms and treated to a dose of 54 Gy in 30 fractions over 6 weeks. Lowenstein Occupational Therapy Cognitive Assessment battery was performed at preradiotherapy baseline, 6 months, and annually thereafter until 5 years. Executive functions measures included orientation, visual perception, spatial perception, motor praxis, visuomotor organization, thinking operations, and attention and concentration. The trajectory of these parameters was compared between the treatment arms over 5 years.ResultsTwo hundred patients were enrolled in the study (SCRT: 104 and ConvRT: 96). The median age was 13 years (interquartile range: 9–17); mean total neurocognitive scores over 5 years were significantly superior in SCRT arm as compared to ConvRT (difference in slope: 2.27, P = .024). Outcomes improved in the SCRT arm vis-à-vis ConvRT for the subdomain of visuomotor organization (difference in slope: 0.66, P < .001). Visuomotor organization scores significantly improved in majority of the substratification groups. Spatial perception improved in craniopharyngioma patients with SCRT technique as opposed to ConvRT.ConclusionsSCRT achieved superior outcomes compared to ConvRT in certain executive neurocognitive functional domains. We provide high level of evidence in favor of SCRT. Trial Registration. ClinicalTrials.gov Identifier: NCT00517959.

108 - Bladder tumors in young patients

108 - Bladder tumors in young patients

Study to evaluate the clinicopathological characteristics and prognostic factors in patients of breast carcinoma below 35 years of age (a study of 200 cases)

Introduction: Breast cancer is one of the most common malignancies among women in most developed and developing regions of the world. In India, breast cancer is the second most common cancer (after cervical cancer). Breast cancer at young age has been reported to have a more aggressive behavior and unfavorable prognosis compared to the older patients. Aims and Objectives: To evaluate prognosis through pathological tumour size, histological grade, mitotic index, lymph node status, distant metastasis and oestrogen & progesterone receptor positivity in young patients ≤ 35 years. Material and Methods: This prospective study was carried out for a period of three years from June 2015 to May 2018. Total of 200 cases of breast carcinoma were studied, out of them patients with ≤35 years were considered as case group and above 35 years of age as control group. Results: Total of 200 cases of breast carcinoma was reported in various age groups in histopathology. Total cases in age group ≤35 years were 28 out of total 200 cases. In age group ≤35 years out of 28 cases, 09 cases showed positive family history, 22 cases showed lymph node metastasis, most common stage of breast carcinoma was stage III, most common histological grade was Grade III and 15 cases were negative for markers ER/PR. Conclusion: Breast cancer is uncommon in young women but it co-relates with a less favorable prognosis. Tumors in younger patients had higher co-morbidity and better screening procedures should be used even in females younger than 35 years of age.

Molecular Pathologic Subtyping of Urothelial Bladder Carcinoma in Young Patients.

Urothelial cancer is a heterogeneous disease with different molecular pathways that produce distinct molecular subtypes with specific characteristics and patient survival outcomes that require different therapeutic methods. Urothelial tumors in young patients appear to have distinct genetic features compared with their counterparts in older patients. Using a Lund subtype-specific immunohistochemistry panel, we performed molecular subtype profiling of an urothelial carcinoma case series (n = 49) in patients younger than 45 years of age. We demonstrate that the urothelial carcinoma in young patients tends to be of molecular urothelial-like A subtype (80%) and is associated with favorable, recurrent-free survival (P = .022). In the urothelial-like cluster, we identified a portion of patients (10%) with high-grade non-muscle-invasive cancers (so-called urothelial-like D type) that showed significantly higher levels of squamous differentiation and p16, E2F3, and ki67 expression in addition to aberrant expression of Ck20 and a trend toward lower recurrent-free survival (P = .057). Segregation of the cohort according to the decade of occurrence revealed that all tumors (n = 8) of patients younger than 30 years were clearly classified as urothelial-like A subtype. Statistically more aggressive molecular subtypes, such as urothelial-like D and basal/squamous-like (6%) subtypes, were identified in patients older than 30 years of age. Genomically unstable (2%) and mesenchymal-like (2%) subtypes were classified in the 40- to 44-year age group only. These data suggest that more aggressive molecular subtypes of bladder carcinoma appear and become more frequent with age. Further investigations are needed to validate this hypothesis.

AIP and MEN1 mutations and AIP immunohistochemistry in pituitary adenomas in a tertiary referral center.

BackgroundPituitary adenomas have a high disease burden due to tumor growth/invasion and disordered hormonal secretion. Germline mutations in genes such as MEN1 and AIP are associated with early onset of aggressive pituitary adenomas that can be resistant to medical therapy.AimsWe performed a retrospective screening study using published risk criteria to assess the frequency of AIP and MEN1 mutations in pituitary adenoma patients in a tertiary referral center.MethodsPituitary adenoma patients with pediatric/adolescent onset, macroadenomas occurring ≤30 years of age, familial isolated pituitary adenoma (FIPA) kindreds and acromegaly or prolactinoma cases that were uncontrolled by medical therapy were studied genetically. We also assessed whether immunohistochemical staining for AIP (AIP-IHC) in somatotropinomas was associated with somatostatin analogs (SSA) response.ResultsFifty-five patients met the study criteria and underwent genetic screening for AIP/MEN1 mutations. No mutations were identified and large deletions/duplications were ruled out using MLPA. In a cohort of sporadic somatotropinomas, low AIP-IHC tumors were significantly larger (P = 0.002) and were more frequently sparsely granulated (P = 0.046) than high AIP-IHC tumors. No significant relationship between AIP-IHC and SSA responses was seen.ConclusionsGermline mutations in AIP/MEN1 in pituitary adenoma patients are rare and the use of general risk criteria did not identify cases in a large tertiary-referral setting. In acromegaly, low AIP-IHC was related to larger tumor size and more frequent sparsely granulated subtype but no relationship with SSA responsiveness was seen. The genetics of pituitary adenomas remains largely unexplained and AIP screening criteria could be significantly refined to focus on large, aggressive tumors in young patients.

Atypical teratoid/rhabdoid tumors of the central nervous system in children: the state of the problem today. Literature review

Atypical teratoid/rhabdoid tumors (AT/RT) are a group of rare highly aggressive malignant tumors in young patients. Among all the malignant tumors of the central nervous system (CNS) in children, they are 1–2 %, which, due to the small number of groups, makes it difficult to develop uniform recommendations for antitumor therapy. The molecular genetic profile of AT/RT, which largely determines the characteristics of the disease, has been studied sufficiently. Despite the large number of ongoing clinical studies, the results of treatment of AT/RT CNS in the world today remain unsatisfactory. The early age of patients limits the use of radiation therapy, which leads to the need to intensify chemotherapy regimens and to choose the optimal strategy in the toxicity – benefit ratio. The article describes modern approaches to the treatment of central nervous system disorders in children, presents the results of studies with the largest number of included patients, using the multimodal treatment strategy, identifies current trends in targeted therapy.Conflict of interest. The authors declare no conflict of interest.Funding. The study was performed without external funding.

Circumscribed choroidal haemangioma: clinical and topographical features

AimsTo characterise the clinical and topographical features of circumscribed choroidal haemangioma (CCH) and to visualise the patterns of tumour extent in the ocular fundus.MethodsData on the size, shape and location...

Frozen Section Diagnosis of Ovarian Epithelial Tumors: Diagnostic Pearls and Pitfalls

Epithelial tumors of the ovary are one of the most frequently encountered gynecologic specimens in the frozen section laboratory. The preoperative diagnostic workup of an ovarian mass is typically limited to imaging studies and serum markers, both of which suffer from low sensitivity and specificity. Therefore, intraoperative frozen section evaluation is crucial for determining the required extent of surgery, that is, cystectomy for benign tumors, oophorectomy or limited surgical staging for borderline tumors in younger patients to preserve fertility, or extensive staging procedure for ovarian carcinomas. Ovarian epithelial tumors may exhibit a wide range of morphologic patterns, which often overlap with each other and can mimic a variety of other ovarian nonepithelial neoplasms as well. A combination of careful gross examination, appropriate sampling and interpretation of morphologic findings, and familiarity with the clinical context is the key to the accurate frozen section diagnosis and successful intraoperative consultation. To review the salient frozen section diagnostic features of ovarian epithelial tumors, with special emphasis on useful clinicopathologic and morphologic clues and potential diagnostic pitfalls. Review of the literature and personal experience of the author. Frozen section evaluation of ovarian tumors continues to pose a significant diagnostic challenge for practicing pathologists. This review article presents detailed discussions of the most common clinical scenarios and diagnostic problems encountered during intraoperative frozen section evaluation of mucinous, serous, endometrioid, and clear cell ovarian tumors.

Coexisting DCIS and phyllodes breast tumors in Young Chinese women: Case series

IntroductionBreast cystosarcoma phyllodes tumors are rare and can be benign or malignant. All sub-divisions of phyllodes tumor—benign, borderline and malignant, can harbor carcinomas, although the incidence is extremely rare. Methods: We present two nonconsecutive cases of coexisting ductal carcinoma in situ (DCIS) and phyllodes breast tumors in young patients. Methods & Case PresentationRetrospective review of two patient’s medical record was performed. Case 130-year-old female underwent excisional biopsy for 3.48 cm mass found on ultrasound. Pathology revealed malignant phyllodes tumor with positive margin. On re-excision, patient was found to have 1.5 cm area of ductal carcinoma in situ (DCIS) with positive margin. Patient then underwent re-reexicision of DCIS with negative margin. Patient underwent chemotherapy and tamoxifen for three years without evidence of disease. Case 230-year-old female presented with 1.3 cm lesion found on ultrasound which core needle biopsy revealed a fibroepithelial tumor. Patient subsequently underwent excision biopsy which found 1.5 cm benign phyllodes tumor and 3.5 mm DCIS within the phyllodes tumor with negative margins. Patient declined additional chemotherapy or hormonal therapy and is currently considering mastectomy. ConclusionPhyllodes tumors are rare and ones with a coexisting carcinoma are even less frequently encountered. The treatment plan can change upon diagnosis of the carcinoma via the pathology. Treatment should be guided by the type and stage of carcinoma detected which may include additional surgical resection and lymph node sampling.