The clinical importance of PD‑L1 and PD‑1 expression in diffuse large B cell lymphoma

Introduction. The target pathway programmed cell death‑1 (PD‑1)/ programmed death‑ligand 1 (PD‑L1) shows clinical efficacy in solid tumors, but also in Hodgkin’s and non‑Hodgkin’s lymphoma. PD‑L1 expression most often correlates with a poor prognosis and a PD‑1 regulatory factor that mediates immunosuppression. The presence of an increased number of tumor‑infiltrating lymphocytes (TILs) PD‑1 + is a favorable prognostic factor in patients with diffuse large B cell lymphomas (DLBCLs) and follicular lymphomas, while the low number of TILs PD‑1 + is associated with an increased risk of histological transformation. In DLBCLs, TILs PD‑1 + may not reflect the depletion of T‑mediated tumor cells but may be an indicator of lymphoid cell origin. Objectives. The objective of this study was to describe the correlation between PD‑1 and PDL‑1 with survival in patients with the diagnosis of diffuse large B cell lymphoma. Material and methods. We have studied 80 patients and we have analyzed DLBCLs according to the Hans algorithm; in addition, we analyzed PD‑1 and PD‑L1 in tumor cells and in immune cells and we correlated this data with patient’s survival. Results. We found that there is a tendency of decreased survival and therapeutic response in DLBCL patients, with both an intense and weak PD‑L1 positivity in tumor cells. PD‑1 low positivity was associated in higher percentage with relapse and treatment unresponsiveness. Conclusions: Our data suggested that PD‑L1 expression correlates with a poor clinical response although it is not an independent prognostic marker and PD‑1 represents a favorable prediction factor for survival

High-grade versus low-grade serous carcinoma of the ovary – current differential diagnosis and perspectives

Introduction. Serous carcinoma is responsible for 47% of all ovarian cancers, and from these cases, only 5% are represented by low-grade serous carcinoma, the rest of them accounting for high-grade serous carcinoma. Objective. The aim of this study is an observational approach of the differences and similarities of the two types of serous carcinoma of the ovary, that must be seen as different forms of cancer and rendered with care. Methods. We performed a retrospective study using three cases of ovarian high-grade serous carcinoma and three cases of ovarian low-grade serous carcinoma, diagnosed at the University Emergency Hospital Bucharest. We analyzed patients’ age, clinical symptoms, macroscopic and microscopic features together with immunohistochemistry tests. Results. Mean age for HG carcinoma was 71.3 years old and for LG carcinoma 47.6 years old. Average tumor diameter was with 5.67 cm higher for LG carcinoma. The most encountered stage for HG tumors was pT2a and for LG tumors was pT1a. Mean value for Ki67 was with 36.33% higher for HG carcinoma. AR expressed diffuse positivity in two cases of LG and only focal positivity in two cases of HG. CD44 expressed focal positivity in all cases of LG and had different patterns in HG. Conclusions. We found considerable differences between patients’ mean age, macroscopic and microscopic features, together with immunohistochemistry expression for Ki67, AR, CD44

Bilateral breast carcinoma – a study of patients admitted in a university emergency hospital

Introduction. Breast carcinoma represents the leading cause of oncologic mortality among women worldwide. Bilateral breast carcinoma is a distinct pathologic entity, with particular prognostic and therapeutic implications. Objective. The objective of the study was to determine the histologic and immunohistochemical characteristics of patients with bilateral breast carcinoma admitted in a university emergency hospital from Bucharest, Romania. Materials and methods. We analyzed breast carcinoma specimens registered as bilateral in the Department of Pathology of the University Emergency Hospital, Bucharest, Romania, between 2015‑2017, and studied their histologic and molecular features in the clinical context obtained from our hospital database. Results. All the analyzed patients were postmenopausal women. The extent of time between the diagnosis of the first and second tumor varied in metachronous cases from 8 months to 7 years. In the majority of cases, the bilateral breast lesions shared histologic, grading and hormone expression similarities. Conclusions. Bilateral breast carcinoma is a rare entity that needs more histologic parameters to be defined as primary or metastatic

Clinico‑morphological aspects and new immunohistochemistry characteristics of ovarian high‑grade serous carcinoma

Introduction. High‑grade serous carcinoma of the ovary is an aggressive form of cancer, with unknown precursor lesions and often delayed diagnosis because of non‑specific, mild symptoms. Objective. We performed a clinical‑pathological study of ovarian high‑grade serous carcinomas, in order to evaluate morphological and new immunohistochemistry characteristics of this malignancy. Methods. This is a retrospective study of 10 cases of ovarian high‑grade serous carcinoma. We evaluated patients’ age, symptoms at presentation, macroscopic aspects, bilateral involvement, microscopic features: papillary/solid areas, mitotic index, psammoma bodies, tumoral extension, lymph node metastasis, immunohistochemistry markers: CD44, ER, AR, Ki67 index. Results. Mean age was 56.9 years old. Tumors were bilateral in 50% of cases. Only 30% were limited to the ovary. Maximum tumor diameter was 16 cm. Solid component in a proportion of 50‑95% was more characteristic. Most tumors had a mitotic index of 30‑50 mitosis/10HPF (70% of cases). 20% of cases contained psammoma bodies. 2 cases out of 7 had lymph node metastasis. We noticed one case with pleural metastasis (M1). We observed AR80% was noticed in 30% of cases. CD44 was positive in 50% of cases and one case had diffuse positivity of CD44 in corpus luteum cells near the tumoral bed. Conclusions. The majority of patients with ovarian high‑grade serous carcinomas presented with extraovarian extension and were characterized by high mitotic index, rare presence of psammoma bodies, AR expression <10%, novel marker CD44 positive in 50% of cases and curious positivity in corpus luteum cells associated with the tumor

BETA-CATENIN – AN IMPORTANT IMMUNOHISTOCHEMICAL TOOL IN STRATIFYING ENDOMETRIAL CARCINOMAS?

Introduction. Recent research has demonstrated that the immunohistochemical nuclear -catenin expression is a valid surrogate for CTNNB1 exon 3 mutation in endometrial carcinomas (ECs). This mutation is an independent prognostic factor which identifies a subgroup of low-grade endometrial carcinomas that have a tendency for recurrence and worse prognosis. The objective of the study was to evaluate nuclear -catenin expression in different molecular subgroups of E Cs. Material and methods. We tested immunohistochemical nuclear -catenin expression in 50 cases of endometrial carcinomas diagnosed in two clinical institutions. Statistical analysis was performed between -catenin expression and various clinical, demographic, pathological and immunohistochemical parameters (age, myometrial invasion, FIGO grade, histopathological subtype, hormone receptors – ER, PR etc). Additionally, we analysed what molecular subgroup of ECs (MSS, MSI, p53wt, p53abn) revealed the most frequent cases with -catenin expression. Results. Our study indicated that ECs with nuclear -catenin positivity were observed in cases with higher FIGO grade (p=0.02), in endometrioid carcinomas (p=0.04) and in cases with lympho-vascular invasion (p=0.05). ER and PR were frequently expressed in the positive -catenin subgroup (p=0.03, p=0 .02). Our results show that ECs which express nuclear -catenin correlate with parameters that are already considered unfavourable. Conclusions. mmunohistochemical -catenin nuclear expression is an excellent replacement for the CTNNB1 exon 3 mutation in ECs and helps to stratify and predict prognosis in certain cases of ECs. We believe that future research will include this marker as part of the routine immunohistochemical panel for ECs

Endoscopic management of a rare case of obstructive giant duodenal Brunner’s gland hamartoma

Introduction. Brunner’s gland hamartomas are very uncommon. They are small, benign lesions, frequently located in the bulb of the duodenum. Usually found incidentally during routine esophago-gastro-duodenoscopies, these lesions are frequently asymptomatic, but some patients may present with symptoms of duodenal obstruction or hemorrhage secondary to ulceration. Surgical excision is required, especially if the lesion has large dimensions. The pathological examination is the most important in confirming the diagnosis.Case presentation. We report a case of a 64-year-old female patient, who presented to the emergency room for vomiting partially digested food, without blood. Upper digestive endoscopy revealed a polypoid mass, with a 1 cm stalk, located in the duodenal bulb. The polyp was successfully endoscopically resected and the pathological diagnosis was of Brunner’s gland hamartoma. Histologically, this polyp consisted of the components of Brunner’s gland cells, as well as glandular, adipose and muscle cells. Conclusions. Brunner’s gland hamartomas are rare duodenal tumors occurring in middle-aged patients that present either with gastrointestinal hemorrhage, obstructive symptoms or as an incidental finding. Surgical or endoscopic excision is uncomplicated, and the long-term outcome is favorable. The particularity of our case is given by the fact that this lesion was very large, it caused symptoms such as vomiting and was managed solely by endoscopic resection

Giant Gallbladder Tumor, Unusual Cancer—Case Report and Short Review of Literature

Background: Giant gallbladder is an uncommon condition that can result from a benign pathology and rarely presents with malignancy. Intracholecystic papillary–tubular neoplasm (ICPN) is a relatively new entity first described by V. Adsay in 2012 and included in the World Health Classification of Digestive System Tumours in 2019. Intracholecystic papillary-tubular neoplasm is a preinvasive lesion with an incidence of around 1% that may present as four histologic subtypes—biliary, gastric, intestinal, or oncocytic—of which the biliary subtype has the highest risk of associated invasive cancer. Although invasive carcinoma is present in about 50% of cases of ICPN, these patients have a significantly better prognosis than those with usual gallbladder cancer, suggesting that the entities may have distinct biological signatures. Case report: A 77-year-old female presented to the hospital with progressive swelling in the right hemiabdomen, a loss of appetite, and weight loss. MRI highlighted a giant abdominal tumor located in the right hypochondrium and right abdominal flank with liver invasion (segment V). Preoperatively, a gallbladder 25 × 17 cm in size was noted, and the patient underwent radical cholecystectomy. It was surprising to find such a giant malignant gallbladder tumor, diagnosed as invasive poorly cohesive carcinoma associated with ICPN. Discussion: A megacholecyst is a rare discovery. Although most often found in benign pathologies, giant gallbladder cancer can be considered. The neoplastic features and the loco-regional extension of the tumor must be evaluated by imaging scans. Few cases of giant benign gallbladder have been reported in the literature; however, this appeared to be the largest resectable gallbladder carcinoma reported to date according to the literature. Conclusion: The stage of gallbladder neoplasia is not correlated with the size of the gallbladder. Regardless of tumor size, the prognosis seems to be directly related to the stage, morphology, and resectability

A RARE ASSOCIATION: ANKYLOSING SPONDYLITIS AND A GENETIC DISEASE

Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease that affects the axial skeleton and sometimes the peripheral joints, leading to the development of bone bridges and ankyloses with impaired joint mobility and quality of life. The HLA B27 antigen, which occurs in approximately 97% of patients, is an important risk factor and also a diagnostic element to consider. The typical onset of the disease is in the 3rd-4th decade of life; juvenile onset of AS under 16 years is associated with the predominant involvement of peripheral joints and multiple complications (coxitis, acute anterior uveitis) which influence the evolution of the disease under treatment being related with a negative prognosis. Noonan syndrome is a genetic disease with dominant autosomal transmission characterized by a small stature and other phenotypic features associated with congenital heart defects, especially pulmonary stenosis and atrial septal defect. Multiple genes within the RAS subfamily involved in various cellular signaling pathways such as signal transmission via mitogen-activated protein kinases are responsible for the occurrence of the disorder. Different hematological diseases such as myeloproliferative syndrome and neoplastic disease, particularly affecting the lung, may be correlated with Noonan syndrome. We present the case of a young patient with juvenile onset AS and Crohn’s disease who has Noonan syndrome with operated pulmonary stenosis and septal atrial defect, the association of these diseases bringing together cumulative complications that required multiple therapies and surgical interventions with strict monitoring

Infiltration pattern predicts metastasis and progression better than the T-stage and grade in pancreatic neuroendocrine tumors: a proposal for a novel infiltration-based morphologic grading

The advancing edge profile is a powerful determinant of tumor behavior in many organs. In this study, a grading system assessing the tumor-host interface was developed and tested in 181 pancreatic neuroendocrine tumors (PanNETs), 63 of which were &lt;=2 cm. Three tumor slides representative of the spectrum (least, medium, and most) of invasiveness at the advancing edge of the tumor were selected, and then each slide was scored as follows. Well-demarcated/encapsulated, 1 point; Mildly irregular borders and/or minimal infiltration into adjacent tissue, 2 points; Infiltrative edges with several clusters beyond the main tumor but still relatively close, and/or satellite demarcated nodules, 3 points; No demarcation, several cellular clusters away from the tumor, 4 points; Exuberantly infiltrative pattern, scirrhous growth, dissecting the normal parenchymal elements, 5 points. The sum of the rankings on the three slides was obtained. Cases with scores of 3-6 were defined as "non/minimally infiltrative" (NI; n = 77), 7-9 as "moderately infiltrative" (MI; n = 68), and 10-15 as "highly infiltrative" (HI; n = 36). In addition to showing a statistically significant correlation with all the established signs of aggressiveness (grade, size, T-stage), this grading system was found to be the most significant predictor of adverse outcomes (metastasis, progression, and death) on multivariate analysis, more strongly than T-stage, while Ki-67 index did not stand the multivariate test. As importantly, cases &lt;=2 cm were also stratified by this grading system rendering it applicable also to this group that is currently placed in "watchful waiting" protocols. In conclusion, the proposed grading system has a strong, independent prognostic value and therefore should be considered for integration into routine pathology practice after being evaluated in validation studies with larger series

Histopathologic infiltration pattern predicts metastasis and progression better than pT-stage and grade in well-differentiated pancreatic neuroendocrine tumors: A proposal for an infiltration-based morphologic grading system

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