MyD88 in osteoclast and osteoblast lineages differentially controls bone remodeling in homeostasis and malaria.

Chronic bone loss is an under-recognized complication of malaria, the underlying mechanism of which remains incompletely understood. We have previously shown that persistent accumulation of Plasmodium products in the bone marrow leads to chronic inflammation in osteoblast (OB) and osteoclast (OC) precursors causing bone loss through MyD88, an adaptor molecule for diverse inflammatory signals. However, the specific contribution of MyD88 signaling in OB or OC precursors in malaria-induced bone loss remains elusive. To assess the direct cell-intrinsic role of MyD88 signaling in adult bone metabolism under physiological and infection conditions, we used the Lox-Cre system to specifically deplete MyD88 in the OB or OC lineages. Mice lacking MyD88 primarily in the maturing OBs showed a comparable decrease in trabecular bone density by microcomputed tomography to that of controls after Plasmodium yoelii non-lethal infection. In contrast, mice lacking MyD88 in OC precursors showed significantly less trabecular bone loss than controls, suggesting that malaria-mediated inflammatory mediators are primarily controlled by MyD88 in the OC lineage. Surprisingly, however, depletion of MyD88 in OB, but not in OC, precursors resulted in reduced bone mass with decreased bone formation rates in the trabecular areas of femurs under physiological conditions. Notably, insulin-like growth factor-1, a key molecule for OB differentiation, was significantly lower locally and systemically when MyD88 was depleted in OBs. Thus, our data demonstrate an indispensable intrinsic role for MyD88 signaling in OB differentiation and bone formation, while MyD88 signaling in OC lineages plays a partial role in controlling malaria-induced inflammatory mediators and following bone pathology. These findings may lead to the identification of novel targets for specific intervention of bone pathologies, particularly in malaria-endemic regions.

Preoperative Magnetic Resonance Imaging Cannot Predict the Presence of a Rare Myoid Gonadal Stromal Testicular Tumor: A Case Report.

Testicular myoid gonadal stromal tumors (MGSTs) are rare neoplasms. While past research has detailed the pathological characteristics of these tumors, the radiological differences between MGST and other types of testicular tumors have not been elucidated. Our study aimed to reveal the possible distinctive features of MGST using magnetic resonance imaging (MRI). We report a 24-year-old patient presenting with a left scrotal mass. During the patient's preoperative MRI, we observed a testicular tumor measuring 2.5 cm that was consistent with the findings of a seminoma. The serum tumor markers were within the normal range. The T1-weighted MRI revealed a solid mass that was isointense-slightly hyperintense compared to the testicular parenchyma, while the mass appeared homogeneously hypointense on the T2-weighted imaging. The patient was planned to undergo left inguinal orchiectomy with the final pathological diagnosis of MGST. The MGST cannot be distinguished from other testicular tumors with certainty based on any MRI findings. The main tool for diagnosis should be based on the histomorphological characteristics and the immunohistochemical profile of the mass.

Failure of sentinel lymph node mapping in a patient with endometrial cancer with chronic lymphocytic leukemia: A case report.

We aimed to report a detection failure of sentinel lymph node (SLN) mapping via indocyanine green in a patient with endometrial cancer with a previous history of chronic lymphocytic leukemia (CLL), which is a potential risk factor to obstruct lymphatic channels. A 64-year-old woman with a 12-year history of CLL presented to the clinic with grade 2 endometrioid carcinoma. The patient underwent laparoscopic surgical staging. Indocyanine green was used intraoperatively to locate the SLN. No lymph node or lymphatic vessels were identified during SLN mapping. At the final pathology, the morphological findings of CLL were detected in the lymph nodes without metastasis of endometrial cancer. Sentinel lymph node mapping failure due to obstruction of lymphatic channels in a patient with CLL was demonstrated in this study. This is the first report to the best of our knowledge showing SLN mapping failure in the presence of lymphoproliferative diseases.

Does it take three to tango? An unsuspected multimorbidity of CD8+ T cell lymphoproliferative disorder, malaria, and EBV infection.

BACKGROUND: Malaria is known to cause acute and deadly complications. However, malaria can cause unforeseen pathologies due to its chronicity. It increases the risk of endemic Burkitt Lymphoma development by inducing DNA damage in germinal centre (GC) B cells, and leading higher frequency of Epstein-Barr virus (EBV)-infected cells in GCs. EBV is well known for its tropism for B cells. However, less is known about EBV's interaction with T cells and its association with T cell lymphoma. CASE PRESENTATION: A 43-year-old Sudanese male admitted to hospital in Istanbul, Turkey, a non-endemic country, with hyperpigmented painful skin rashes on his whole body. A complete blood count and a peripheral blood smear during admission revealed large granular lymphocytes (LGLs) with abnormally higher CD8 T cell numbers. Additional skin biopsy and pathology results were compatible with CD8+ T cell lymphoproliferative disorder with skin involvement. Patient was treated and discharged. However, a pathologist noticed unusual structures in skin tissue samples. Careful evaluation of skin biopsy samples by polarized microscopy revealed birefringent crystalloid structures resembling malarial haemozoin mainly loaded in macrophages and giant histiocytes. After purification of DNA from the skin biopsy samples, nested PCR was performed for the detection of Plasmodium parasites and Plasmodium falciparum DNA was amplified. Because, the co-presence of EBV infection with malaria is a well-known aetiology of lymphoma, EBV-early RNA (EBER) transcripts were investigated in paraffin-embedded tissue samples and found to be positive in macrophage-like histiocytes. CONCLUSIONS: This is a unique case of malaria and EBV infection in a T-LGL lymphoma patient who presented in a non-endemic country. This case emphasizes the clinical importance of EBV monitoring in T-LGL patients with skin involvement. Notably, Plasmodium infection should be examined in patients from malaria endemic regions by pathological and molecular investigations.

Diagnostic challenges in cutaneous leishmaniasis due to atypical Leishmania infantum: pathologists' insights from re-emergence zones.

Background: Leishmaniasis, a parasitic infection affecting both humans and animals, is increasingly spreading across Mediterranean and European regions, largely driven by human migration and environmental changes. In countries like Türkiye and across Europe, which have seen large influxes of migrants, the incidence of cutaneous leishmaniasis (CL) is rising, with cases now appearing in cities where the disease was previously undocumented. In these previously non-endemic areas, physicians unfamiliar with the characteristic lesions may misdiagnose CL, particularly in cases with only cutaneous manifestations. This study aims to evaluate the impact of re-emerging CL on the routine diagnostic practices of pathologists in Türkiye, by retrospectively reviewing cases. Methods: We conducted a retrospective analysis of CL cases diagnosed between 2013 and 2022 at a single pathology center in Türkiye, covering multiple provinces. Twelve cases of CL were identified and analyzed based on clinical presentation, pre-diagnosis, histopathological findings, and molecular diagnostics. DNA extraction and PCR were performed on paraffin-embedded tissue samples to identify the Leishmania species involved. Results: Out of the twelve CL cases reviewed, seven exhibited morphological findings strongly suggestive of CL (MFSS of CL), warranting further microbiological evaluation. All patients presented with non-healing skin lesions characterized by central ulceration, crater-like formations, or papulonodular lesions. Notably, CL was included in the clinical pre-diagnosis in only 58.3% of cases, while it was not considered in the remaining 41.7% of cases. Clinicians initially pre-diagnosed skin tumors in six cases (50%), four of which led to wide surgical excision. Histopathological examination in all cases revealed chronic or mixed (acute/chronic) inflammation, predominantly rich in histiocytes. To further investigate the role of Leishmania species in the pre-diagnosis, DNA extraction and PCR were performed on paraffin-embedded tissue samples, identifying L. infantum as the causative agent in 10 cases and L. major in two cases. Notably, L. infantum was the causative agent in all five cases initially misdiagnosed as skin tumors, which were also associated with a granulomatous type of chronic inflammation.

The Programmed Cell Death Ligand 1 and Lipocalin 2 Expressions in Primary Breast Cancer and Their Associations with Molecular Subtypes and Prognostic Factors.

Purpose: Breast cancers exhibit molecular heterogeneity, leading to diverse clinical outcomes and therapeutic responses. Immune checkpoint inhibitors targeting PD-L1 have shown promise in various malignancies, including breast cancer. Lipocalin 2 (LCN2) has also been associated with tumor aggressiveness and prognostic potential in breast cancers. However, the expression of PD-L1 and LCN2 in breast cancer subtypes and their prognostic implications remains poorly investigated. Methods: A retrospective analysis of 89 primary breast cancer cases was conducted to assess PD-L1 and LCN2 expressions using immunohistochemistry. Cases were classified into four different molecular subtypes based on ER, PR, HER2, and Ki-67 status. Associations between PD-L1 and LCN2 expressions and various prognostic factors were examined. Results: Although low expression of LCN2 (Allred score of <3) was observed even in normal breast tissue, LCN2 expression with increasing Allred score (≥3) positively correlated with the histological grade, high Ki-67 proliferation index, and ER/PR negativity. Significant elevations of LCN2 and PD-L1 expressions were observed in triple-negative and HER2-positive breast cancers. Conclusion: The results of the study highlight the association of LCN2 with known prognostic factors and molecular subtypes. To identify potential immunotherapy recipients, it would be useful to evaluate LCN2 as well as PD-L1 immune targets in different subgroups of breast cancer patients. Further studies with larger patient numbers are warranted to validate these observations and establish standardized scoring criteria for LCN2 expression assessment.

Endometrial Staining of CD56 (Uterine Natural Killer), BCL-6, and CD138 (Plasma Cells) Improve Diagnosis and Clinical Pregnancy Outcomes in Unexplained Infertility and Recurrent IVF Failures: Standardization of Diagnosis with Digital Pathology.

In women with unexplained infertility (UI) and recurrent in vitro fertilization (IVF) failures, the etiology is often unclear. Endometrial immune perturbations and the use of immune markers associated with these dysregulations are of great interest in the diagnosis and treatment of UI. However, reliable biomarkers and standardized quantification methods are lacking. Here, to address endometrial immune dysregulation in UI patients with recurrent IVF failures, we performed endometrial tissue sampling and immunostaining of CD56 (uNK), CD138, and BCL-6. Of these cases, 57.9% had positive CD56 in the endometrial stroma, while 46.1% had positive BCL-6 in the glandular epithelium, and 14.5% of the cases were found to be positive for CD138. Combined staining rates were 60.5%, 68.4%, and 71.05% for (CD56 or BCL-6), (CD56 or CD138), and (CD56, BCL-6, or CD138), respectively. There was a significant correlation between CD56 and BCL-6 positivity, while CD138 positivity was an independent parameter. After the recommended targeted therapy, pregnancy rates were found to increase from 58.5% to 61.6% and 73.8% in CD56-positive, (CD56- or BCL-6-positive), and (CD56-, BCL-6-, or CD138-positive) cases, respectively. Notably, a retrospective evaluation of digital pathology and light microscopy results showed a significant correlation. This study suggests that the examination of CD56, BCL-6, and CD138 in the same endometrial sample may be an effective method in determining the etiology of UI and reaching an early diagnosis and treatment options. Moreover, digital pathology can be used in the evaluation of CD56 and BCL-6 to provide objective, rapid, and reliable results.

Systemic Sarcoidosis Induced by Chemotherapy, Mimicking Metastatic Testicular Carcinoma with 18F-FDG PET/CT

A 34-year-old male patient who had left orchiectomy and received three cycles of chemotherapy for testicular mix germ cell carcinoma was referred for 18fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for complaints of weight loss and fever. PET/CT showed multiple and progressive 18F-FDG uptakes in supra and infra diaphragmatic lymphatic regions, and multiple abnormal 18F-FDG uptakes were noted in the lytic formed skeletal lesions. Clinicians remain in doubt regarding the multiple metastatic lesions without elevated serum tumor marker levels (alpha-fetoprotein, beta-human chorionic gonadotrophin, CA19-9, and carcinoembryonic antigen). Biopsy of the lytic lesion in the iliac bone revealed granulomatous inflammation suggestive of sarcoidosis. Systemic prednisone at 20-40 mg/daily was started. 18F-FDG PET/CT images showed complete metabolic response to prednisone 8 months following the start of treatment.

An Unusual Schwannoma in the Proximal Forearm: A Case Report.

Schwannomas are common, well-encapsulated benign tumors of the peripheral nerves. They rarely emerge from the median nerve in the forearm. Here we report a case of an unusual schwannoma measuring 3 × 4 × 3 cm originating from the median nerve in the proximal forearm of a 49-year-old man. The mass was painless, but Tinel's sign was positive. Ultrasonography showed a solid, hypoechoic mass with central cystic areas in the flexor muscle group in the left forearm. Magnetic resonance imaging with contrast enhancement in T1 sequences revealed that it originated from the median nerve. Surgical resection was performed by separating the nerve fibers from the tumor without any complications. Histological examination confirmed it as a schwannoma.

Successful laparoscopic management of a rare complication after embryo transfer: ovarian pregnancy. A case report and up-to-date literature review.

Ovarian pregnancy (OP) after embryo transfer is very rare. Due to the rarity and the asymptomatic nature, there are still difficulties in diagnosis and treatment. The traditional operative treatment for OP has been oophorectomy. However, the desire to maintain reproductive capability and improvements in laparoscopy have more recently led to conservative laparoscopic techniques. This rare complication could be diagnosed early and managed by a conservative laparoscopic approach. Here we present a survey of the literature and a case of successful laparoscopic management of ovarian pregnancy after intracytoplasmic sperm injection and embryo transfer. The current case is the first case in the literature in which ovarian pregnancy occurred after a single embryo transfer. We also summarize the literature about management of ovarian pregnancy after embryo transfer.

Why did the patient die? The relationship between ambulance accidents and death of patients: forensic medical issues.

This article's aim is investigating traumatic consequences of ambulance accident on patients and discussing difficulties to give a decision about the relation between death and accident at these cases. The cases were selected among the forensic medical reports concluded between 1996 and 2005 years. They were documented for age, sex, causes of urgent call, localization and extent of traumatic lesion, properties of events and board decisions. A total of 21 cases were found. 15 cases died on the day of the accident. Skin injuries at head (8 cases) and legs (6 cases) were most common traumatic lesions. Totally 6 deaths were found related with ambulance accident. Death of patient after ambulance accidents may not be associated easily to the accident. Delay due to accident or concomitant contributing medical conditions may also facilitate the death in this type of cases. Reliable medical records were needed for accurate medicolegal evaluation.