Head and neck INI1-deficient carcinoma without primary: a case report.

BACKGROUND: SMARCB1, also known as INI1, is a member of a large protein complex involved in chromatin remodeling and thus the regulation of gene expression. It is located on chromosome 22q11.2. SMARCB1 tumors have been found in various locations, including the sinonasal region, gastrointestinal tract, central nervous system (in atypical teratoid and rhabdoid tumors), and perirenal region (in malignant rhabdoid tumors) in both adults and children. CASE PRESENTATION: We describe here the first case in the literature of an INI1-deficient neck carcinoma without a primary tumor managed with surgical therapy and neck dissection in a young Caucasian woman of 29 years old, followed by chemotherapy before radiotherapy, with regional control after 18 months of follow-up. Histologic analysis showed an undifferentiated carcinoma without glandular or epidermoid differentiation. Biomolecular analysis of the tumor revealed a homozygous deletion of the SMARCB1 gene on RNA sequencing. CONCLUSION: Research of INI1 deletion should be performed for undifferentiated carcinoma of young patients because of possibilities of molecular therapies such as autophagy inhibitors or proteasome inhibitors could be used in clinical trials.

Absolute Lymphocyte Count After COVID-19 Vaccination Is Associated with Vaccine-Induced Hypermetabolic Lymph Nodes on 18F-FDG PET/CT: A Focus in Breast Cancer Care.

We aimed to predict the presence of vaccine-induced hypermetabolic lymph nodes (v-HLNs) on 18F-FDG PET/CT after coronavirus disease 2019 (COVID-19) vaccination and determine their association with lymphocyte counts. Methods: In this retrospective single-center study, we included consecutive patients who underwent 18F-FDG PET/CT imaging after messenger RNA- or viral vector-based COVID-19 vaccination between early March and late April 2021. Demographics, clinical parameters, and absolute lymphocyte count (ALC) were collected, and their association with the presence of v-HLNs in the draining territory was studied by logistic regression. Results: In total, 260 patients were eligible, including 209 (80%) women and 145 (56%) with breast cancer. The median age was 50 y (range, 23-96 y). The messenger RNA vaccine had been given to 233 (90%). Ninety (35%) patients had v-HLNs, with a median SUVmax of 3.7 (range, 2.0-26.3), and 74 (44%) displayed lymphopenia, with a median ALC of 1.4 × 109/L (range, 0.3-18.3 × 109/L). An age of no more than 50 y (odds ratio [OR], 2.2; 95% CI, 1.0-4.5), the absence of lymphopenia (OR, 2.2; 95% CI, 1.1-4.3), and less than a 30-d interval from the last vaccine injection to the 18F-FDG PET/CT (OR, 2.6; 95% CI, 1.3-5.6) were independent factors for v-HLNs on multivariate analysis. In breast cancer patients, the absence of lymphopenia was the only independent factor significantly associated with v-HLNs (OR, 2.9; 95% CI, 1.2-7.4). Conclusion: Patients with a normal ALC after COVID-19 vaccination were more likely to have v-HLNs on 18F-FDG PET/CT, both of which might be associated with a stronger immune response to vaccination.

Breast MR biopsy: Pathological and radiological correlation.

PURPOSE: To identify pathological features for sample analysis of magnetic resonance imaging-guided vaccum-assisted breast biopsy (MRIgVaBB) to optimize radio pathological correlation and identify discordant benign result. MATERIAL AND METHODS: Databases of two centres were queried to identify MRIgVaBB performed between January 2009 and February 2013. A cohort of 197 women (mean age: 54.5 years (24-77)) with 208 lesions was identified. We retrospectively analyzed all prebiopsy MRI examinations according to the new BI-RADS lexicon, and all biopsy samples to describe the lesion of interest, its interface with the surrounding breast tissue and other associated features. RESULTS: The malignancy rate was 26.0 % (54/208) with an underestimation rate of 15.67 % (5/32). A visible interface at pathology between a biopsied lesion and the surrounding breast tissue was more frequently identified in mass enhancement compared to NME or focus (p = 0.0003). Regional NME was correlated with a high degree of fibrosis (p = 0.001) and the presence of PASH (p = 0.0007). Linear or segmental NME was correlated with the presence of periductal mastitis (p = 0.0003). CONCLUSION: The description of a visible interface between the target lesion and the surrounding tissue is crucial to confirm the correct targeting of an MR mass or a NME. KEY POINTS: • Pathological interface correlated with magnetic resonance mass and focal non-mass enhancement (NME). • Linear or segmental NME correlated with mastitis or ductal carcinoma in situ. • Fibrosis and pseudoangiomatous stromal hyperplasia (PASH) are correlated with regional NME.

Supervised clustering of immunohistochemical markers to distinguish atypical and non-atypical endometrial hyperplasia.

The risk of endometrial hyperplasia (EH) progressing into endometrioid endometrial cancer ranges from 1% for simple EH without atypia (EHWA) to 46.2% for atypical EH (AEH). Differentiation between both entities is crucial to determine optimal management. As preoperative diagnosis of AEH can be difficult, we aimed to establish clusters of immunohistochemical markers to distinguish EHWA from AEH. We studied 13 immunohistochemical markers (steroid receptors, pro/anti-apoptotic proteins, metalloproteinases (MMP), tissue inhibitor of metalloproteinase (TIMP), CD44 isoforms) known for their role in endometrial pathology. Using supervised clustering, we determined clusters of co-expressed proteins which contributed the most in differentiating EHWA from AEH. From 39 tissue samples (17 EHWA and 22 AEH), we found three clusters of co-expressed proteins: Cluster 1 included two proteins (over-expression of estrogen receptor (ER) and under-expression of progesterone receptor (PR) B in AEH compared to EHWA); Cluster 2: an ER, PR A, MMP-2 and TIMP-1 over-expression and a PR B and TIMP-2 under-expression; Cluster 3: over-expression of ER and MMP-7 and under-expression of PR B and TIMP-2. AEH can be accurately distinguished from EHWA using a supervised clustering of immunohistochemical markers. This promising approach could be useful to improve the preoperative diagnosis of EH.

Supervised clustering of immunohistochemical markers to distinguish atypical endometrial hyperplasia from grade 1 endometrial cancer.

OBJECTIVES: Differentiation between grade-1 endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) is crucial to determine optimal surgical management. However, discrepancies exist between preoperative diagnosis of AEH and final histology. Our aim was to establish clusters of immunohistochemical markers to distinguish AEH from grade-1 EC. METHODS: We studied 13 immunohistochemical markers (steroid receptors, pro/anti apoptotic proteins, metalloproteinases (MMP) and tissue inhibitor of metalloproteinase (TIMP), and CD44 isoforms) known for their role in endometrial pathology. Using supervised clustering, we determined clusters of co-expressed proteins which contributed the most in differentiating grade-1 EC from AEH. RESULTS: From 42 tissue samples (20 ECs and 22 AEHs), we found 3 clusters of co-expressed proteins: Cluster 1 included 3 proteins (over-expression of MMP-9 and under-expression of estrogen receptor (ER) and progesterone receptor (PR) A in grade-1 EC compared to AEH); cluster 2 showed an MMP-9 over-expression and ER under-expression; cluster 3 showed over-expression of MMP-9 and bcl-2 and under-expression of ER, PR A and CD44-v6 variant. These three clusters together predicted grade-1 EC with a misclassification rate of 8%. CONCLUSION: Supervised clustering of immunohistochemical markers in grade-1 EC and AEH tissue identified proteins acting together and resulted in accurate differentiation between these two histological entities.

Expression of IL-27 by tumor cells in invasive cutaneous and metastatic melanomas [corrected]..

Interleukin (IL)-27 is a cytokine of the IL-12 family that displays either immunostimulatory or immunosuppressive functions depending on the context. In various murine tumor models including melanoma models, ectopic expression of IL-27 has been shown to play an anti-tumoral role and to favor tumor regression. In this study, we investigated whether IL-27 might play a role in the development of melanoma in humans. We analyzed the in situ expression of IL-27 in melanocytic lesions (n = 82) representative of different stages of tumor progression. IL-27 expression was not observed in nevus (n = 8) nor in in situ melanoma (n = 9), but was detected in 28/46 (61%) cases of invasive cutaneous melanoma, notably in advanced stages (19/23 cases of stages 3 and 4). In most cases, the main source of IL-27 was tumor cells. Of note, when IL-27 was detected in primary cutaneous melanomas, its expression was maintained in metastatic lesions. These in situ data suggested that the immunosuppressive functions of IL-27 may dominate in human melanoma. Consistent with this hypothesis, we found that IL-27 could induce suppressive molecules such as PD-L1, and to a lesser extent IL-10, in melanoma cells, and that the in situ expression of IL-27 in melanoma correlated with those of PD-L1 and IL-10.

Histological and immunohistochemical profiles predict lymph node status in women with low-intermediate risk endometrial cancer.

OBJECTIVE: The aim of this study was to build a model to predict the risk of lymph node metastases (LNM) in women with low- or intermediate-risk endometrial cancer (EC) using histological and immunohistochemical markers. METHODS: Samples were collected from 68 women with low- or intermediate-risk EC. European Society of Medical Oncology (ESMO) risk group, lymphovascular space involvement (LVSI), immunostaining expressions of Estrogen receptor (ER) and Progesteron receptor (PR) were used to build a recursive partitioning model to predict final lymph node status. RESULTS: The number of women with final low- and intermediate risk EC was 34 (50%) each. LVSI was present in 7 women with low-risk (20%) and 28 (80%) with intermediate-risk EC. Nineteen women (28%) had LNM at final histology. A lower immunostaining of ER (p=0.02) and PR (p=0.03) was found in women with LNM compared with those without. Women were correctly classified by the model in 87% of cases; among the 56 women without LNM that were predicted, 48 (86%) had no LNM at final histology. Among the 12 women with LNM predicted, 11 (92%) had LNM at final histology. CONCLUSIONS: Our results show that lymph node status can be predicted with a relatively high accuracy in women with low- or intermediate-risk EC. This can help physicians to better adapt surgical staging and adjuvant therapies.

Expression of follicle-stimulating hormone receptor by the vascular endothelium in tumor metastases.

BACKGROUND: The Follicle Stimulating Hormone receptor (FSHR) is expressed by the vascular endothelium in a wide range of human tumors. It was not determined however if FSHR is present in metastases which are responsible for the terminal illness. METHODS: We used immunohistochemistry based on a highly FSHR-specific monoclonal antibody to detect FSHR in cancer metastases from 6 major tumor types (lung, breast, prostate, colon, kidney, and leiomyosarcoma ) to 6 frequent locations (bone, liver, lymph node, brain, lung, and pleura) of 209 patients. RESULTS: In 166 patients examined (79%), FSHR was expressed by blood vessels associated with metastatic tissue. FSHR-positive vessels were present in the interior of the tumors and some few millimeters outside, in the normally appearing tissue. In the interior of the metastases, the density of the FSHR-positive vessels was constant up to 7 mm, the maximum depth available in the analyzed sections. No significant differences were noticed between the density of FSHR-positive vessels inside vs. outside tumors for metastases from lung, breast, colon, and kidney cancers. In contrast, for prostate cancer metastases, the density of FSHR-positive vessels was about 3-fold higher at the exterior of the tumor compared to the interior. Among brain metastases, the density of FSHR-positive vessels was highest in lung and kidney cancer, and lowest in prostate and colon cancer. In metastases of breast cancer to the lung pleura, the percentage of blood vessels expressing FSHR was positively correlated with the progesterone receptor level, but not with either HER-2 or estrogen receptors. In normal tissues corresponding to the host organs for the analyzed metastases, obtained from patients not known to have cancer, FSHR staining was absent, with the exception of approx. 1% of the vessels in non tumoral temporal lobe epilepsy samples. CONCLUSION: FSHR is expressed by the endothelium of blood vessels in the majority of metastatic tumors.

Eutopic endometrium and peritoneal, ovarian and colorectal endometriotic tissues express a different profile of nectin-1, -3, -4 and nectin-like molecule 2.

STUDY QUESTION: How is the expression of nectins and nectin-like molecules (Necls) detected by immunostaining altered by endometriosis? SUMMARY ANSWER: Our results suggest that Nectin-1, -3, -4 and Necl-2 may contribute to the pathogenesis of endometriosis. Immunostaining of nectins and Necls varies according to the anatomical location of endometriosis. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Nectin and Necl molecules are immunoglobulin-like cell adhesion molecules involved in apoptosis, cell proliferation and in metastases. Previous studies have demonstrated the involvement of adhesion molecules in the development of endometriotic lesions but no data exist on immunostaining of nectins and Necls molecules in endometriosis. DESIGN, PARTICIPANTS AND SETTING: This retrospective study was conducted in a tertiary-care hospital (Tenon Hospital, Paris, France). Samples were collected from 55 women undergoing endometrial biopsy or surgery for endometriosis and 20 controls having hysterectomy or endometrial biopsy for other reasons; multiple samples were collected from 15 women. We studied the immunostaining of Nectin-1, -3, -4 and Necl-2 in secretory and proliferative endometrium from women with (n = 20) or without endometriosis (i.e. control group, n = 20), and in peritoneal (n = 20), ovarian (n = 20) and colorectal endometriosis (n = 20). MAIN RESULTS: Semi-quantitative immunostaining demonstrated that (1) Necl-2 staining was stronger in all types of endometriotic lesions than in the eutopic endometrium from patients with endometriosis (P < 0.0125) and in ovarian endometriotic cysts compared with other locations (P < 0.001); (2) Nectin-3 staining was stronger in the eutopic endometrium of patients with endometriosis compared with controls (P = 0.03) and in all endometriotic lesions compared with the eutopic endometrium from patients with endometriosis (P < 0.0125); (3) Nectin-4, staining was stronger in the eutopic endometrium of patients with endometriosis compared with controls (P = 0.04) and (4) Nectin-1 staining was significantly increased in colorectal endometriosis compared with other locations (P = 0.004). BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: We did not assess the pattern of expression in endometriosis of all nectins and Necl molecules. Indeed, Necl-5 is implicated in many pathophysiological processes such as cell movement and proliferation with potential relevance to endometriosis. GENERALISABILITY TO OTHER POPULATIONS: At present, few data on implication of nectins and Necl molecules in endometriosis exist. Hence, our results should be confirmed by further quantitative studies at protein or RNA levels. STUDY FUNDING/COMPETING INTEREST(S): No funding source. All the authors declare no conflict of interest.

Epstein-Barr virus-induced gene 3 (EBI3): a novel diagnosis marker in Burkitt lymphoma and diffuse large B-cell lymphoma.

The distinction between Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), two types of mature aggressive B-cell lymphomas that require distinct treatments, can be difficult because of forms showing features intermediate between DLBCL and BL (here called BL/DLBCL). They can be discriminated by the presence of c-myc translocations characteristic of BL. However, these are not exclusive of BL and when present in DLBCL are associated with lower survival. In this study, we show that Epstein-Barr virus-induced gene 3 (EBI3) is differentially expressed among BL and DLBCL. Analysis of gene expression data from 502 cases of aggressive mature B-cell lymphomas available on Gene Expression Omnibus and immunohistochemical analysis of 184 cases of BL, BL/DLBCL or DLBCL, showed that EBI3 was not expressed in EBV-positive or -negative BL cases, whereas it was expressed by over 30% of tumoral cells in nearly 80% of DLBCL cases, independently of their subtypes. In addition, we show that c-myc overexpression represses EBI3 expression, and that DLBCL or BL/DLBCL cases with c-myc translocations have lower expression of EBI3. Thus, EBI3 immunohistochemistry could be useful to discriminate BL from DLBCL, and to identify cases of BL/DLBCL or DLBCL with potential c-myc translocations.

[An unusual adrenal tumor: Ewing tumor]. / Une tumeur surrénalienne inhabituelle : tumeur d'Ewing.

We report the case of a voluminous tumor of the adrenal diagnosed in a young pregnant woman at 26(th) week of amenorrhea. Morphologically, a soft white tumor with haemorragic areas was observed, made of sheets of monomorphous, medium sized, spindle-shaped to polygonal, with high mitotic activity. Tumorous cells expressed cytokeratins AE1/AE3, EMA, and CD99 (expression of vimentin is not relevant). Contemplated diagnoses included poorly differentiated synovialosarcoma, sarcomatoid carcinoma and Ewing tumor. Thanks to molecular biology, showing the specific transcript of Ewing/peripheral primitive neuroectodermal tumor (pPNET) EWS/FLI1, the diagnosis of this atypical tumor in an unusual location was performed. Indeed, 75% of Ewing tumors involve bones (especially, the diaphysis of long bones) and 20 to 25% soft tissues. Primitive visceral involvement is rare; less than 10 cases of adrenal involvement have been reported. The hypothesis that Ewing cell's origin is a mesenchymal stem cell, which may derive from neural crest cell, could explain the uncommon adrenal involvement. Diagnosis of Ewing tumor is based on pathologic and molecular findings, especially in atypical cases.

Cervical Metastasis From Colorectal Cancer.

Metastatic carcinoma from colorectal cancer to the uterine cervix is rare. We report a case of metastatic carcinoma from a right colon cancer to the cervix with vaginal extension 3 years after primary treatment. Our report highlights the importance of immunohistochemical analysis to determine the origin of uterine cervix cancer in the event of adenocarcinoma in a patient with a history of colorectal cancer to adapt therapeutic strategy accordingly.

Cardiac contusion and hemopericardium in the absence of external thoracic trauma: case report and review of the literature.

The case of an unusual homicidal cardiac contusion is described. A previously healthy 24-year-old woman suddenly died after being kicked on the chest by her boyfriend. A forensic autopsy was performed showing no external sign of thoracic trauma. An hemopericardium and a cardiac contusion of the basal and posterior surface of the left ventricle were found to be the cause of the death. Death could be a direct consequence of the myocardial contusion through electrical instability or/and consequence of the hemopericardium because its volume and sudden apparition were sufficient to cause tamponade. Numerous associated recent skin contusions mainly located on the face were consistent with inflicted blunt force trauma, supporting homicide as a manner of death. This case report underlines the importance of a systematic complete autopsy in all cases of sudden death occurring in a young adults, to rule out a possible homicide. The present case also shows that myocardial injury must be ruled out in every living patient presenting blunt chest trauma even in the absence of external sign.