Primary Histiocytic Sarcoma of the Breast: A Case Report and Review of the Literature.

Histiocytic sarcoma (HS) is a rare cancerous tumor that originates from fully developed histiocytes. It is most often identified by the presence of certain proteins such as the cluster of differentiation (CD) 68, CD163, or lysozyme. HS has been recorded in different sites outside of the lymph nodes such as the gastrointestinal tract, nasal cavities, skin, and bone marrow. Because HS shares similar clinical features with other forms of malignant diseases, diagnosing it becomes incredibly challenging. We report a case of a 40-year-old female who presented with a breast mass for one year. A preliminary diagnosis of a phyllodes tumor was made. However, the morphology along with the immunophenotype picture was diagnostic for HS. Microscopic features showed a well-defined neoplastic growth arranged in sheets and fascicles. Diffuse immunoreactivity was seen for CD45, CD4, CD68, CD163, and vimentin. We present the important histopathological and immunohistochemical characteristics of the tumor in this case.

Prevalence of CEA, CA 125, and CA 15-3 serum tumour markers in different regions of Saudi Arabia.

OBJECTIVES: To study the prevalence of tumor marker (TM) carcinoembryonic antigen (CEA), cancer antigen 125 (CA 125), and cancer antigen 15-3 (CA 15-3) levels in the Saudi population, based on gender, age, and demographic region, and whether the patients were referred by a hospital or self-referred. METHODS: Retrospective analysis was carried out on 7,019 samples gathered from the Western, Northern, Central, Southern, and Eastern regions of Saudi Arabia between 2021-2022. The TMs were categorized into normal and abnormal levels, according to the reference ranges. Statistical analysis was carried out to assess the relations between variants (age groups, gender, and demographic regions) using the Chi-square test, and their correlations were assessed using Spearman's test. RESULTS: Among all patients, CEA, CA 125, and CA 15-3 levels were found to be significantly correlated with age (p=0.0001). The CEA and CA 15-3 levels increased in both males and females with age. The CA 125 was shown to have an abnormally increased level in males with age. CONCLUSION: Increased levels of CEA, CA 125, and CA 15-3 TMs in the study population were significantly correlated with age. The CEA and CA 15-3 levels were within the normal range, while CA 125 levels were above the normal range in the older male population. These results suggest that the utilization of such TMs is age dependent and would have validity if applied with other parameters.

Expression of p16 protein in breast cancer.

Breast cancer is the most common cancer and a leading cause of death in women in Saudi Arabia. P16 is a tumour suppressor gene that plays a crucial role in regulating cell cycle. Several studies have investigated the significance of p16 expression in various cancer types. However, the significance of p16 in breast cancer remains controversial and insufficiently studied. The present study aims to examine the association between p16 expression and clinicopathological factors in breast cancer using immunohistochemistry staining. The study utilised 475 prospectively collected tissue samples from 475 women with breast cancer in Saudi Arabia. Nuclear and cytoplasmic immunohistochemical staining of p16 was observed in 338 (71%) of the cases and showed significant direct associations with adverse tumour features, including high tumour grade (p < 0.0001), negative oestrogen receptor/progesterone receptor status (p < 0.001), and lymph node metastasis (p = 0.02). Our study revealed a significant association between p16 protein expression and the established negative prognostic parameters in breast carcinoma including tumour grade, lymph node metastasis, and oestrogen receptor and progesterone receptor status.

Adenomatoid tumor of the adrenal gland: unexpected guest.

Adenomatoid tumor (AT) is a benign growth that originates from mesothelial cells. Typically, it encompasses the uterus, fallopian tubes, and paratesticular area. One-third of all AT is in paratesticular area, and it accounts for 60% of all benign paratesticular tumors. ATs have been seldom reported as a case report in adrenal gland, liver, pleura, and mediastinal cavity. To date, English literature has only documented 46 instances of adrenal AT. We present the occurrence of a new clinically unexpected case of adrenal AT in a 37-year-old male patient. Computed tomography (CT scan) incidentally revealed the presence of a tumor. To the best of our knowledge, this is the first reported instance of primary adrenal gland AT reported in Saudi Arabia and the 47th instance worldwide in the English-based published literature. It is crucial to thoroughly investigate these tumors, utilizing techniques such as histopathological analysis and immunohistochemical staining to correctly diagnose AT.

Survivin expression is associated with lymph node metastasis and short survival in patients with colorectal adenocarcinoma.

BACKGROUND: Survivin, a protein belonging to the Inhibitor of apoptosis (IAP) family, is the smallest member in terms of size. It works by preventing programmed cell death and regulating the advancement of the cell cycle. Being a part of the group of inhibitors associated with apoptosis, survivin is connected to increased aggression and negative prognosis in different malignancies, including colorectal cancer (CRC). MATERIALS AND METHODS: Pathology tissue blocks of 209 primary tumors, and 44 adenomas, were used in this study, as well as an anti-Survivin antibody. A semiquantitative method was used to score the Survivin expression based on an evaluation of the percentage and intensity of nuclear expression. RESULT: Survivin expression was identified in 127 (60.8%) CRC samples and in 14 adenomas (31.8%). There was an association between positive Survivin immunostaining and lymph node metastasis (P: 0.001), lymphovascular invasion (P: 0.020), and short overall survival (Log-rank 4.012, P=0.045) and disease-free survival probabilities (Log Rank 4.921, P=0.027). There was no association between Survivin expression and age, gender, tumor location, size, stage, margin status, and tumor recurrence. CONCLUSION: Survivin immune expression is associated with worse prognoses in CRC patients. Survivin can be a potential disease biomarker and could be used in management plans for CRC patients.

Primary pancreatic lymphoma: Histopathological pattern of 8 cases.

OBJECTIVES: To report the histopathological pattern of primary pancreatic lymphoma (PPL) in 2 tertiary hospitals. METHODS: The pathology slides and reports of all the cases diagnosed in pathology departments in 2 referral hospitals were reviewed. An additional immunohistochemistry study was done to reclassify lymphomas according to the current system. RESULTS: Eight patients with PPL have been identified. The ages ranged from 36 to 71 years. Clinical presentation includes abdominal pain, weight loss, jaundice, abdominal mass, nausea, and vomiting. Pathological evaluation revealed 5 diffuse large B-cell lymphomas, one high-grade B-cell lymphoma, one MALT lymphoma, and one follicular lymphoma. CONCLUSION: Primary pancreatic lymphoma is a very rare tumor without specific clinical, laboratory tests, or radiological findings. Abdominal pain is the most common clinical presentation. Diffuse large b-cell lymphoma is the most common pathological subtype. Primary pancreatic lymphoma should be taken into consideration when evaluating pancreatic mass to avoid unnecessary surgical resection.

Identification of SPP1 as a Prognostic Biomarker and Immune Cells Modulator in Urothelial Bladder Cancer: A Bioinformatics Analysis.

Secreted phosphoprotein-1 (SPP1) expression is differentially altered in many malignancies and could serve as a potential prognostic biomarker. Recent findings indicated that SPP1 possesses a broader role in bladder cancer (BC) pathogenesis than previously envisioned; however, the underlying mechanisms governing its expression, cellular localization, prognostic value and immune-related role in bladder cancer remain poorly understood. The expression and the prognosis value of SPP1 were assessed using immunohistochemistry (IHC) staining on a tissue microarray. SPP1 expression was correlated with the clinicopathological parameters, and survival analysis was calculated using a Kaplan-Meier plotter. Bioinformatics analysis of TCGA data was queried using UALCAN, CIBERSORT and TIMER datasets to decipher the biological processes enrichment pattern, protein-protein interactions and characterize tumor-infiltrating immune cells, respectively. IHC revealed that SPP1 expression is significantly associated with tumor type, stage, grade and smoking status. The Kaplan-Meier survival curve showed that low SPP1 expression is an unfavorable prognostic indicator in bladder cancer patients (p = 0.02, log-rank). The significant increased expression of the SPP1 level is associated with evident hypomethylation of the gene promoter in cancer compared to normal tissues in the TCGA-bladder dataset. Missense mutation is the most frequent genetic alteration of the SPP1 gene. Protein-protein interactions demonstrated that SPP1 shares the same network with many important genes and is involved in many signaling pathways and biological processes. TIMER reported a significant correlation between SPP1 expression and multiple immune cells infiltration. Furthermore, the expression of SPP1 was found to be positively correlated with a number of immune checkpoint genes such as PD-1 and CTLA4. The current investigation indicates that the SPP1 protein could serve as a prognostic biomarker and merit further investigation to validate its clinical usefulness in patients with bladder cancer.

Extracranial Medulloblastoma With Myogenic Differentiation: Report of a Rare Event.

Medulloblastoma accounts for nearly 10% of childhood primary central nervous system (CNS) malignancies. However, it is rare in adults. Extracranial metastasis is commonly documented to involve bones but rarely involves lymph nodes. Herein, we present an unusual case of primary CNS medulloblastoma in an adult patient with extracranial metastasis to a lymph node, which exhibits a myogenic differentiation. To the best of our knowledge, this is the fourth reported case of medulloblastoma in an adult with extracranial metastasis to the lymph node and the first reported case of extracranial metastatic medulloblastoma with myogenic differentiation that involves a lymph node.

Prognostic value of glucose transporter proteins-1 (GLUT1) in breast carcinoma.

Several studies have reported increased glucose transporters (GLUT) expression in different cancer types, including breast cancer. The primary purpose of this study is to examine GLUT1 immunoexpression in breast cancer patients in Saudi Arabia and to determine its significance. The study examined the association between GLUT1 immunophenotype and the clinicopathological characteristics in breast cancer. GLUT1 expression was analyzed in retrospectively collected tissue samples (n = 578) from breast cancer patients using immunohistochemistry. A total of 311 (54%) of the cases expressed GLUT1 cytoplasmic immunohistochemical staining. In univariate analysis, we found a significant association between GLUT1 expression and high-grade tumors (p < 0.0001). Positive estrogen and progesterone receptor results predicted lower GLUT1 immunoexpression (p < 0.0001 for both). Vascular invasion showed a significant association with GLUT1 immunoexpression (p = 0.045). Our findings support that GLUT1 immunohistochemistry can be used as a marker to determine the grade and hormonal receptor status in breast cancer.

Composite Lymphoma's Ability to Adapt and Change Through Plasticity: A Case Report and Literature Review.

Composite/synchronous lymphoma is an uncommon condition that presents a challenge in histopathological diagnosis due to the simultaneous appearance of two or more lymphomas, including instances where they are intermixed within the same location. Performing a core needle tissue biopsy adds a challenge for pathologists when trying to diagnose a condition that requires excisional tissue for a thorough evaluation. This report highlights a distinctive instance of composite lymphoma in which classical Hodgkin lymphoma (cHL) is combined with diffuse large B-cell lymphoma (DLBCL). All pertinent information including clinical, histopathological, and immunohistochemical data for each of these composite lymphomas is provided. In addition, we conducted a literature review of the published data. The findings from these data further support the theory of a shared clonal origin and transdifferentiation occurrence in the process of lymphoma development.

Expression pattern, prognostic value and potential microRNA silencing of FZD8 in breast cancer.

Breast cancer (BC) is one of the most widespread types of cancer affecting females, and therefore, early diagnosis is critical. BC is a complex heterogeneous disease affected by several key pathways. Among these, WNT proteins and their frizzled receptors (FZD) have been demonstrated to be crucial in regulating a number of cellular and molecular events in BC tumorigenesis. The role of the WNT receptor, FZD8, in BC has received minimal attention; for that reason, the present study examined the prognostic value of its protein expression pattern in a BC cohort. FZD8 cytoplasmic expression pattern analysis revealed that ~38% of the primary samples presented with a high expression profile, whereas ~63% of the samples had a low expression profile. Overall, ~46% of the malignant tissues in the lymph node-positive samples exhibited an increased FZD8 cytoplasmic expression, whereas 54% exhibited low expression levels. An increased expression of FZD8 was associated with several clinicopathological characteristics of the patients, including a low survival rate, tumor vascular invasion, tumor size and grade, and molecular subtypes. Affymetrix microarray triple-negative BC datasets were analyzed and compared with healthy breast tissues in order to predict the potential interfering microRNAs (miRNAs) in the WNT/FZD8 signaling pathway. A total of 29 miRNAs with the potential to interact with the WNT/FZD8 signaling pathway were identified, eight of which exhibited a significant prediction score. The target genes for each predicted miRNA were identified. On the whole, the findings of the present study suggest that FZD8 is a potential prognostic marker for BC, shedding some light onto the silencing mechanisms involved in the complex BC signaling.

Histopathological Experience of Primary Adrenal Lymphoma From Two Tertiary Hospitals.

INTRODUCTION:  Primary adrenal lymphoma (PAL) is a rare tumor. The aim of this study was to demonstrate the histopathological features of PAL at two tertiary hospitals. MATERIALS AND METHODS:  All PALs diagnosed between January 2003 and February 2023 were retrieved. Pathology and immunohistochemistry slides were reviewed. Additional immunohistochemical markers were done in selected cases. Follow-up data were obtained. RESULTS:  There were 7 cases of PAL. The age range of the patients was 52 to 73 years (median 64 years; mean 63.3 years). There were 4 males (57.1%) and 3 females (42.9%). The clinical manifestations included abdominal pain nausea, vomiting, and loss of weight. There were 4 cases of diffuse large B-cell lymphoma (DLBCL), 2 cases of high-grade B-cell lymphomas, and 1 case of follicular lymphoma. There were 5 cases that were unilateral and 2 cases that were bilateral, and both were high-grade B-cell lymphoma. During follow-up, the 1-year and 2-year overall survival rates were 50% and 33%, respectively. CONCLUSION:  PAL is a disease of the elderly, and DLBCL is the most common pathological type. The prognosis is generally poor. Further reporting of PAL cases might help in understanding this disease and could lead to improvement in its management.

Adenomatous hyperplasia of rete testis diagnosis on testicular biopsy for primary infertility: A case report.

Adenomatous hyperplasia of rete testis is a rare non-neoplastic proliferation of rete testis epithelium. Mostly as an incidental finding in orchiectomy specimen for cryptorchidism and germ cell tumors. However, AHRT in testicular biopsies is rarely reported in the literature. The pathogenesis of AHRT is not fully understood yet. AHRT usually arises near the mediastinum and septal portion of the rete testis. Herein, we report an interesting finding of AHRT in a testicular biopsy performed for infertility workup. Practicing pathologists must be aware of this entity and the differential diagnosis as it might pose a diagnostic challenge during histological evaluation.

Primary Esophageal Lymphoma: A Histopathological Experience from Two Tertiary Hospitals, Western Saudi Arabia.

Background: Primary esophageal lymphoma (PEL) is a rare disorder. The objective of this study was to document the clinicopathological features of PEL at two tertiary hospitals in the western region of the Kingdom of Saudi Arabia. Methods: All PELs diagnosed between May 2002 and June 2022 were retrieved. Histopathological and immunohistochemical slides were reviewed. Additional immunohistochemistry stains were performed in selected cases. Follow-up data were collected. Results: There were only eight cases of PEL in the records of the two hospitals. The age of the patients ranged between 50 and 74 years (median 62 years and mean 62.5 years). There were six males (80%) and two females (20%). None of the patients were immunocompromised or had human immunodeficiency virus (HIV) infection. The clinical manifestation included dysphagia and loss of weight. Six cases were diffuse large B-cell lymphoma (DLBCL), and two were low-grade mucosa-associated lymphoid tissue lymphoma. Conclusion: PEL is an extremely rare disease with male predominance. DLBCL is the most common pathological type in our community. There was no relation to immune status or HIV infection in this series. Clinical presentations were typically dysphagia with weight loss. Further reporting of PEL cases might help explain this disease and improve its diagnosis and management.

Clinical significance of galectin-3 expression in urinary bladder carcinoma.

OBJECTIVE: To uncover the clinical significance of galectin-3 in the evolution of urinary bladder cancer by defining galectin-3 expression and examining the relationship between its expression in a group of urothelial carcinomas versus normal tissues along with clinicopathological factors. METHODS: This retrospective study included histopathological reports and archival blocks and slides of all patients with urinary bladder cancer treated at King Abdulaziz University Hospital (Jeddah, Saudi Arabia). An anti-galectin-3 monoclonal antibody was used for immunohistochemical staining of tissue microarray slides comprising 128 cases of urothelium carcinoma and 24 specimens of normal bladder mucosa. RESULTS: Galectin-3 was downregulated during transformation, with positive expression found in 50 (39%) urinary bladder neoplasms, of which 33 (66%) showed weak immunostaining. All positively-stained malignant tumor and normal bladder mucosa samples showed cytoplasmic staining; a few samples also showed nuclear staining. No correlation was noted between galectin-3 and histotype, grade, stage, muscularis propria invasion, lymph node invasion, vascular invasion, or metastasis. A Cox proportional hazards model and Kaplan-Meier survival curves did not show differences in survival on the basis of galectin-3 expression. CONCLUSION: Galectin-3 is down-regulated in bladder cancer but is not a helpful marker for the diagnosis or prognosis of urinary bladder cancer.

Primary lymphoma of the kidney: Pathology experience from 2 tertiary hospitals in Western Saudi Arabia.

OBJECTIVES: To document the clinicopathological features of primary renal lymphoma (PRL) at 2 tertiary hospitals in the western region of the Kingdom of Saudi Arabia. METHODS: Data were retrieved from all PRLs that were diagnosed at King Abdulaziz University Hospital and King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia, between January 2002 and April 2022. Histopathological and immunohistochemical slides were reviewed, and additional immunohistochemistry stains were carried out in selected cases. Follow-up data were also collected. RESULTS: There were 17 identified cases of PRL. The age of the patients ranged from 4-76 years (median: 50.5 years and mean: 46.8 years), 11 (64.7%) were males, and 6 (35.3%) were females. There were 12 cases of diffuse large B-cell lymphoma, 3 cases of Burkitt's lymphoma, and 2 cases of post-transplant lymphoproliferative disorder. The median follow-up duration was 22 months. The one-year overall survival rate was 71% and the 2-year overall survival rate was 43% during follow-up. CONCLUSION: Primary renal lymphomas in Saudi patients are more common in males and seen in a relatively younger age group compared to the available worldwide data. The diagnosis of PRL is important to avoid tumor dissemination and unnecessary nephrectomy. Diffuse large B-cell lymphoma is the most common pathological type and non-germinal center B-cell is the most common subtype.

CD10 expression in urinary bladder urothelial carcinoma is associated with high-tumor grade and stage.

Objectives: Primary urinary bladder carcinoma is a common cancer worldwide. There is limited published data about CD10 immunoexpression pattern in urothelial bladder carcinoma (UBC). This study aims to examine CD10 immunoexpression in UBC and evaluate its relationship with clinicopathological parameters. Methods: The retrospective study examined 130 samples of UBC tissue and 30 samples of non-neoplastic urothelial bladder tissue, which were obtained from the Anatomic Pathology Department, King Abdulaziz University, Jeddah, Saudi Arabia. The project started in June 2019 and completed in February 2021. Tissue microarrays (TMA) were prepared from paraffin blocks and tissue sections prepared from the recipient blocks were used for immunohistochemistry studies utilizing CD10 antibody. The immunostaining results were recorded and analyzed. Results: Positive staining of CD10 was observed in 64 (49%) cases of UBC and was not detected in any non-neoplastic urothelium samples. CD10-positive staining was identified in 36.7% and 66.7% of low and high-grade tumors, respectively. There was an association between positive CD10 immunostaining and high tumor grade (p=0.006) and muscularis propria invasion (p=0.007). There was no association between CD10 immunoexpression and age, gender, nodal and distant metastasis, lymphovascular invasion, and tumor recurrence. CD10 immunoexpression was not associated with the probabilities of overall survival (log rank 1.663, p=0.197) or disease-free survival (log rank 1.637, p=0.201). Conclusions: In UBC, CD10 immunoexpression is associated with higher tumor grade and muscle invasion, but it is not associated with patient survival or other clinicopathological parameters. CD10 immunoexpression cannot be used as a biomarker for poor prognosis in UBC.

Solid Pseudopapillary Neoplasm of the Pancreas: A Clinicopathological Study of 12 Cases With Emphasis on Diagnostic Pitfalls.

INTRODUCTION: Solid pseudopapillary neoplasm of the pancreas (SPNP) is a rare primary neoplasm with distinct clinicopathological features. The tumor most commonly occurs in younger (premenopausal) women and is typified by low malignant potential and an excellent overall prognosis. METHODS: A retrospective search over 20 years at two referral tertiary care institutions (King Faisal Hospital and Research Center and King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia) revealed 12 female patients diagnosed with SPNPs. The reslts of ancillary studies performed at the time of diagnosis were also reviewed and placed in the context of current recommendations. RESULTS: The clinical and pathological findings were reviewed. All patients were females, aged 18 to 30 years. Eight patients presented with abdominal pain, of which two experienced significant weight loss, and four presented with abdominal mass/discomfort. The tumor size ranged from 1.5 and 15 cm. Two cases were initially diagnosed as neuroendocrine tumors (NETs). One of the cases presented as a multifocal disease. All patients were treated surgically with a follow-up period between one and 11 years. Only one patient presented with peritoneal metastasis after seven years of follow-up, but generally, all are doing well. CONCLUSIONS: We have analyzed 12 SPNP cases in our population over 20 years (2001-2021) in this study. In brief, SPNP is a low-grade malignant potential tumor. Even though SPNP is a recognized entity, diagnostic challenges can arise particularly in the setting of limited sampling. Pathologists must be aware of the classic morphological features of SPNP and the characteristic profile of immunohistochemistry and be able to differentiate SPNP from other mimickers, especially well-differentiated NETs of the pancreas, and ultimately to avoid misdiagnosis and unnecessary oncologic treatment. Adequate surgical resection with negative margins is associated with an excellent outcome.

Genotype-Phenotype Correlation of a Rare Transthyretin Variant Causing Amyloidosis.

Left ventricular hypertrophy is a common entity with a broad differential diagnosis. We present a case of a middle-aged woman with left ventricular hypertrophy and neuropathy caused by a rare transthyretin variant in the absence of a family history or regional reports of hereditary transthyretin amyloidosis. This report outlines the diagnosis and management of patients with a mixed phenotype of hereditary transthyretin amyloidosis and enriches clinical data supporting the pathogenicity of a rare variant of transthyretin.

L'hypertrophie ventriculaire gauche est une entité clinique fréquente pour laquelle le diagnostic différentiel est vaste. Nous décrivons le cas d'une femme d'âge moyen présentant une hypertrophie ventriculaire gauche et une neuropathie, causées par un variant rare de la transthyrétine en l'absence d'antécédents familiaux ou de cas régionaux déclarés d'amylose héréditaire à transthyrétine. Le présent article décrit le diagnostic et la prise en charge des patients qui présentent un phénotype mixte d'amylose héréditaire à transthyrétine, et il alimente le bassin de données cliniques sur la pathogénicité d'un variant rare de la transthyrétine.

High COX-2 immunostaining in papillary thyroid carcinoma is associated with adverse survival outcomes.

BACKGROUND: Thyroid carcinoma is one of the most common malignancies worldwide. More than 70%-80% are papillary thyroid carcinoma (PTC). Many factors influence the PTC pathway of development such as genetic mutations, growth factors, and radiation. More biological understanding of the genetic and molecular pathways is needed in PTC to determine tumor behavior, and initial clinical assessment. OBJECTIVES: Investigate the relation of COX-2 immunostaining in thyroid carcinoma with clinicopathological parameters to assess whether immunostaining results have prognostic significance. DESIGN: Retrospective study SETTING: Pathology department, tertiary care center METHODS: Records of PTC were retrieved and tissue microarrays were constructed. Tissue sections were stained using anti-human COX-2 monoclonal antibody. Immunostaining results were recorded and analysed. MAIN OUTCOME MEASURES: Relationship of COX-2 immunostaining in thyroid carcinoma with clinicopathological parameters. SAMPLE SIZE: 139 tissue samples from 139 patients RESULTS: High versus low COX-2 immunostaining showed no significant differences for most clinicopathological parameters. However, high COX-2 immunostaining showed borderline association with tumor multifocality (P=.05), lower overall (log-rank=8.739 and P=.003), and disease-free survival (log-rank=7.033, P=.008). CONCLUSION: The study showed a positive association of high COX-2 immunostaining with lower survival outcomes in PTC. COX-2 immunostaining could be a potential prognostic factor for survival in PTC. Additional molecular and clinical investigations are needed for further understanding the molecular pathways of COX-2 in PTC and the feasibility of using inhibitors of COX-2 as adjuvant therapy along with current chemotherapy. LIMITATIONS: Relatively low number of PTC variants, and no testing of other thyroid carcinomas. CONFLICT OF INTEREST: None.