The impact of MYD88 and PIM1 in mature large B-cell non-Hodgkin lymphomas: Defining element of their evolution and prognosis.

Sequence studies of the entire exome and transcriptome of lymphoma tissues have identified MYD88 and PIM1 as involved in the development and oncogenic signaling. We aimed to determine the frequency of MYD88 and PIM1 mutations, as well as their expressions in conjunction with the clinicopathological parameters identified in mature large B-cell non-Hodgkin lymphomas. The ten-year retrospective study included 50 cases of mature large B-cell lymphoma, diagnosed at the Pathology Department of the Emergency County Hospital of Constanta and Sacele County Hospital of Brasov. They were statistically analyzed by demographic, clinicopathological, and morphogenetic characteristics. We used a real-time polymerase chain reaction technique to identify PIM1 and MYD88 mutations as well as an immunohistochemical technique to evaluate the expressions of the 2 genes. Patients with lymphoma in the small bowel, spleen, brain, and testis had a low-performance status Eastern Cooperative Oncology Group (P = .001). The Eastern Cooperative Oncology Group performance status represented an independent risk factor predicting mortality (HR = 9.372, P < .001). An increased lactate dehydrogenase value was associated with a low survival (P = .002). The international prognostic index score represents a negative risk factor in terms of patient survival (HR = 4.654, P < .001). In cases of diffuse large B-cell lymphoma (DLBCL), immunopositivity of MYD88 is associated with non-germinal center B-cell origin (P < .001). The multivariate analysis observed the association between high lactate dehydrogenase value and the immunohistochemical expression of PIM1 or with the mutant status of the PIM1 gene representing negative prognostic factors (HR = 2.066, P = .042, respectively HR = 3.100, P = .004). In conclusion, our preliminary data suggest that the oncogenic mutations of PIM1 and MYD88 in our DLBCL cohort may improve the diagnosis and prognosis of DLBCL patients in an advanced stage.

Endometrial Osseous Metaplasia-A Rare Cause of Infertility with Unknown Etiology.

Background: Osseous tissue in the endometrium is a rare find, and it is most often discovered when the patient presents with infertility. It is frequently associated with dysmenorrhea and abnormal menstrual bleedings. Although its etiology remains unclear, in almost all described cases until now, the patient has an obstetrical history. Case report: In this report, we present a unique case of endometrial osseous metaplasia in a 27-year-old primary infertile patient. The transvaginal ultrasound revealed a 18/13/7 mm hyperechoic endometrial mass with posterior acoustic shadowing and no flow on color Doppler. A hysteroscopic examination found a polygonal calcification on the endometrial posterior face of the uterine cavity, in the corporeal isthmic region, which was extracted. The histopathological evaluation revealed microscopic elements compatible with endometrial calcification. The patient had a good postoperative course and the complex endocrinologic, immunologic and electrolytical investigation failed to prove any abnormality. Follow-up transvaginal ultrasound examinations revealed no modifications. Three years later, the patient conceived spontaneously, had an uneventful pregnancy and delivered a full-term fetus. Conclusion: We assumed that this entity can be a serious cause of infertility since the patient had a long history of (primary) infertility and its resection made the pregnancy's occurrence possible. Finally, since neither history of abortion or chronic inflammation nor any abnormal laboratory test were noticed, we concluded that the etiology of this entity remained unclear.

Comparison of Ki67 Proliferation Index in Gastrointestinal Non-Hodgkin Large B-Cell Lymphomas: The Conventional Method of Evaluation or AI Evaluation?

The most common NHL subtype in SEEU is DLBCL (39%), and it manifests with a variety of cellular morphologies and a high proliferation index. Also, the GI tract is the most common site of extranodal NHLs, and most NHLs involving the GI tract are of B-cell lineage, of which diffuse large B-cell lymphoma is the most common subtype, irrespective of location. The last few years have seen digital pathology as a vital technology that has a positive impact on diagnostics, but studies on the use of DP for lymphoma identification, however, are still restricted to only determining whether a tumor is present or absent. Using the example of cases of malignant NHL, we aim to investigate the diagnostic utility of DP using QuPath software in evaluating the proliferation index and the prognostic significance and to show that improved visualization and analysis contribute to the convergence of these complementary diagnostic modalities for lymphomas. The average proliferation index (Ki67) was 58.33% with values between 10% and 85%. After the stratification of the cases, an increased proliferation index was observed in the majority of cases (53.33%), and this aspect was associated with the advanced age of the patients (p = 0.045). Visual assessment provides lower Ki67 values than automated digital image analysis. However, the agreement coefficient between the conventional method and the AI method indicates an excellent level of reliability (ICC1-0.970, ICC2-0.990). The multivariate analysis revealed that in the cases where the proliferation index Ki67 is high (˃70%), the IPI score represents an important risk factor predicting mortality (HR = 10.597, p = 0.033).

HER2 Negative Mammary Paget's Disease or In Situ Melanoma? A Case Report and Review of the Literature.

Mammary Paget's disease (MPD) is a rare histological condition, accounting for 1-4% of female breast cancers, which may appear either independently (1.4-13% of the cases), or in association with an in situ or invasive ductal carcinoma (approximately 90% of the cases). The purpose of this article is to highlight the histopathological challenges related to the microscopical polymorphism of this disease and the utmost importance of immunohistochemistry in the thorough process of Paget's disease differential diagnosis. Moreover, the primary objective of this review of literature was to corroborate the existing data concerning the potential peculiar immunohistochemical profile that mammary Paget's disease might express. We report the case of a 44-year-old female patient, histopathologically diagnosed with HER2-negative MPD accompanying an invasive mammary carcinoma. The histopathological and immunohistochemical approach is derived from the exigency of excluding the possibility of synchronous tumors-a mammary invasive carcinoma, accompanied by another component with MPD phenotypic mimicry. The unexpected negative HER2 reaction is conducted to a primary focus on excluding a malignant melanoma in situ. The absence of MelanA and S100 immunoexpression and lack of pigmentation and clinical aspects infirmed it. Bowen's disease was invalidated by its rare presentation in the breast cutaneous tissue and the absence of individual risk factors suggestive of an existing immunosuppressive status. In the case of similar morphoimmunohistochemical aspects, significant expression of Ki-67 signals MPD, an immunoreactivity that helped distinguish the cellular population from Toker cells. The great similarity of MPD with other benign and malignant cutaneous tumors might determine delay or misdiagnosis. Thus, the utmost importance of immunohistochemistry is reflected in its prognostic significance and geared towards extending the therapeutic arsenal.

The Malignant Gastrointestinal Neuroectodermal Tumor (GNET): A Distinct Entity and the Challenging Differential Diagnosis with Mesenchymal, Lymphoid, and Melanic Tumors: A Case Report and Brief Review of the Literature.

(1) Background: A malignant gastrointestinal neuroectodermal tumor (GNET) is an ultra-rare primary neoplasm with a distinctive histopathological, immunohistochemical, molecular, and ultramicroscopic profile, synonymous terminology with clear cell sarcoma-like tumor of the gastrointestinal tract. This case report aims to describe a case of GNET with challenging mesenchymal, lymphoid, and melanic tumor differential diagnosis. (2) Case presentation: We discuss the case of a 67-year-old male patient who presented with diffuse abdominal pain, intermittent lack of intestinal transit, and frequent episodes of nausea, followed by segmental resection of the jejunum and sigmoid colon. The patient had no relevant medical history. The surgical specimen underwent immunohistochemical staining and morphological evaluation. (3) Results: Histopathological analysis reveals a moderately homogeneous polyhedral-epithelioid and spindle cell neoplastic proliferation with a zonal discohesive pattern and extensive and focal fasciculated architecture. Twenty monoclonal antibodies were used for immunostaining, which allowed GNET to be diagnosed on the basis of the tumoral immune profile, characterized by positive reactivity of S100, SOX10, and CD 56. (4) Conclusions: The poor prognosis of GNET is highlighted in the present study, along with the vital importance of differential diagnosis issues with mesenchymal, lymphoid, and melanic tumors, which make the diagnosis difficult for both pathologists and clinicians.

Diffuse large B cell lymphoma CD5-positive arising in an immune deficiency and immune dysregulation setting: A case report and brief review of the literature.

RATIONALE: In the era of antiretroviral therapy, lymphoma is the primary cause of cancer-related death among human immunodeficiency virus (HIV)-infected people and the most prevalent and aggressive non-Hodgkin lymphoma is diffuse large B cell lymphoma, which usually has an aggressive clinical course. CD5-positive diffuse large B cell lymphoma (DLBCL) is an insufficiently studied, relatively new entity, which accounts for 5% to 10% of the DLBCL population. The current study presents the clinicopathological features, diagnostic approach, and clinical outcomes of this HIV-related lymphoma and highlights the importance of the early diagnosis of CD5-positive DLBCL. PATIENT CONCERNS: We present a case of a 30-year-old male patient, with a medical history of HIV-positive serology and antiviral treatment, presenting with diffuse abdominal pain and symptoms related to obstruction or perforation, followed by exploratory laparotomy and surgical resection of the small intestine with other areas of involvement. The surgical specimen was morphologically evaluated and immunohistochemical stained. DIAGNOSES AND INTERVENTIONS: Histopathologic examination revealed a diffuse neoplastic proliferation of large B lymphocytes within the small intestine, lacking features of other defined types of large B cell lymphoma. The diagnosis of CD5-positive DLBCL subtype was made after immunostaining with twelve monoclonal antibodies (CD3, CD5, CD10, CD20, CD23, CD30, CD68, Cyclin D1, MUM1, Bcl2, Bcl6, and Ki-67). The expression profile of immunohistochemical markers (CD10, Bcl6, and MUM1) established the cell of origin of this case of DLBCL by using the Hans algorithm. LESSONS: The current report highlights the importance of early diagnosis of CD5-positive DLBCL because of its poor prognosis and calls attention to the critical importance to identify immunodeficiencies because doing so affects the types of treatments available. Although cell-of-origin is useful for predicting outcomes, the germinal center B cell like and activated-B cell like subtypes remain heterogeneous, with better, and worse prognostic subsets within each group.

Online Doc: Is Social Media Education a Tool for Melanoma Prevention? A Survey-Based Analysis Among Romanian Digitally Active Users.

BACKGROUND: In the contemporary era, people are extracting medical information from content-sharing means on the Internet, and the most popular virtual platforms authorize users to access knowledge, guidance, and exchange opinions. Doctors have massively joined online communities and developed educational accounts to meet the informational necessities of general users. The aim of the current study is to identify the role of social media in augmenting the awareness of melanoma. METHODS: For this observational study, questionnaires were disseminated to the general population over eight weeks consecutively, through online channels, represented by Facebook (Meta Platforms, Inc., Menlo Park, California, United States) and Instagram (Meta Platforms, Inc., Menlo Park, California, United States), to extract qualitative data related to the relationship between social media, the epidemiological variables, and melanoma-associated/sun protection behaviors. The inclusion criteria comprised constant Facebook and Instagram users, aged between 18-65. RESULTS: The study included 221 individuals, primarily aged 26 to 35 (47.1%), mostly females (77.82%). Urban dwellers (>200,000 inhabitants) constituted the majority (71.94%), contrasting with a small rural representation (3.61%). Nearly half actively followed medical educational content online (44.79%), while 12.66% avoided online medical advice. Sun-protective habits were prevalent, with 80.99% using SPF (sun protection factor), 54.29% wearing UV-filter (ultraviolet-filter) sunglasses, and 53.84% avoiding sun exposure between 10 AM and 4 PM. Respondents rated sun-protective measures, with the highest average for avoiding sun exposure during peak hours being 7.3 on a scale of 1 to 10. Dermatological advice from social media influenced behaviors, such as SPF use (50.67%) and sun exposure avoidance (45.7%). Dermatological check-ups were infrequent, with 49.32% sporadically visiting a dermatologist. Dermoscopic evaluations were rare (36.66%), with 27.14% using it preventively. Personal and family history of dysplastic nevi and melanoma were low. CONCLUSIONS: This study provides insights into the dermatological behaviors and education of individuals engaging with social media medical content. The results suggest that constant users of social media harbor a receptive attitude toward dermatological advice provided on specific platforms, hence creating an ideal environment for further dissemination and organization of online skin cancer awareness campaigns.

Proteomics and genomics of a monomorphic epitheliotropic intestinal T-cell lymphoma: An extremely rare case report and short review of literature.

RATIONALE: Monomorphic epitheliotropic intestinal T-cell lymphoma, formerly known as enteropathy-associated T-cell lymphoma, is an extremely rare, aggressive peripheral extranodal T-cell lymphoma, that is infrequent in native European and Caucasian populations. The current study presents the clinicopathological features, diagnostic approach, and clinical outcomes of this rare entity of lymphoma and highlights the importance of the early diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL). PATIENT CONCERNS: Main symptoms and/or important clinical findings: We present the case of a 69-year-old male patient presenting with an abdominal mass, intestinal transit disorder, and weight loss. The abdominal computed tomography (CT) revealed features suggestive of a malignancy. Following clinical and imaging investigations, surgical resection of the small intestine with other areas of involvement has been performed and further to the histopathological examination and immunohistochemical testing are mandatory. DIAGNOSES AND INTERVENTIONS: Histopathological evaluation of the tumor revealed a proliferation of medium- to large-sized monomorphic lymphocytes, with vesicular nuclei, prominent nucleoli, and a moderate amount of clear to pale eosinophilic cytoplasm, with an association of infrequent Reed-Sternberg-like cells. Immunohistochemical assessment of the aforementioned tumor using CD3, CD8, CD5, CD20, and CD30 confirmed the T cell proliferation line and the monomorphic epitheliotropic intestinal T-cell lymphoma diagnosis. LESSONS: The current report highlights the importance of early diagnosis of MEITL owing to its poor prognosis and presents histopathological features that help distinguish MEITL from inflammatory bowel diseases and less aggressive T-cell lymphomas.

Morphological and Ancillary Features of Uterine Leiomyosarcoma: Case Report.

We report a rare case of giant uterine leiomyosarcoma in a postmenopausal woman, whose diagnosis was initially suspected at the evaluation of the abdominal efusion, and confirmed after the pathological examination of the uterus in association with the ancillary tests. The evaluation of the abdominal fluid showed single or clusters of malignant, round or spindle-shaped cells. On microscopic examination of the surgical specimen, a dense cell proliferation of spindle cells, with moderate to severe nuclear pleomorphism and significant mitotic activity was observed. Immunohistochemical evaluation demonstrated the loss of myocytic differentiation by focal, weakly positive expression of smooth muscle actin and desmin. The data presented in this case emphasize the relevance of the cytological examination, although the latter has only indicative value, especially since it is an aggressive tumor, frequently associated with mutant expression of p53. In our case, the first indication of the presence of uterine sarcoma was given by the presence of atypical cells in the peritoneal fluid.

Concurrent Tumors Revealed by an Autopsy-A Case Report and Literature Review.

Introduction: Multiple primary malignant neoplasms are an uncommon phenomenon, given the very low incidence of two or more different tumors, while neoplasm may be limited to a single organ or may involve multiple separate anatomical organs. The main purpose of this study is to highlight the importance of morphological and immunohistochemical tests to distinguish the origin of the primary tumor. Case Presentation. We report the case of a 65-year-old deceased male, presenting multiple tumors in the lung, stomach, kidneys, and adrenal organs. The main symptoms presented by the patient were dyspnea with a range of 77% with oxygen saturation, fatigability, and productive cough. Histopathological examination revealed a solid and papillary lung adenocarcinoma, concurrent with tubular gastric adenocarcinoma. Immunohistochemical testing was mandatory by using a panel of seven monoclonal mouse antibodies (TTF-1, Napsin A, CK7, CK20, p40, synaptophysin, and chromogranin A). The pulmonary tumoral immunophenotype (positive for TTF-1, Napsin A, CK7; negative for CK20, p40, synaptophysin, and chromogranin A) confirms the diagnosis of primary lung ADC and invalidates the hypothesis of a metastasis arisen from a gastric adenocarcinoma or other forms of lung cancer. Conclusion: The importance of the ancillary test is to distinguish a primary tumor from a metastatic one.

Dinosaur Tail Appendix in Trisomy 13.

BackgroundAmong the many malformations associated with trisomy 13, one of the less recognized is dinosaur tail appendix. Case report: We illustrate a dinosaur-tail appendix from an autopsy in a newborn female with trisomy 13. This malformation has a frequency between 0.014% and 3.7% in general population. Conclusion: Trisomy 13 is a relatively well-known chromosomal disorder in which dinosaur tail appendix can be found. This entity should be considered element of a complete morphological diagnosis.