Papillary Renal Cell Carcinoma with Extensive Spindle Cell Foci: Mimicker of Mucinous Tubular and Spindle Cell Carcinoma

Introduction/Objective Papillary Renal Cell Carcinoma (PRCC), the 2nd most common RCC, accounts for 10-15% of cases and is usually composed of tubules and papillae with foamy histiocytes in papillary cores. Mucinous tubular and spindle cell carcinoma (MTSC) is composed of tightly packed, elongated, curvilinear tubules with smooth luminal surfaces, separated by mucinous stroma. MTSC is associated with a more favorable prognosis than PRCC. PRCC and MTSC have significant histologic and histochemical overlap including elongated tubules and stromal Alcian blue positive mucin deposits. Methods/Case Report We report a case of a 75 year old female who underwent a robotic assisted partial nephrectomy for resection of a 5.7 x 5.2 x 5.0 cm left upper pole solid renal mass. Spindle cell change with elongated tubules reminiscent of MTSC was present in several blocks; however, the luminal surface was shaggy favoring PRCC. Patchy prominent extracellular Alcian blue positive mucin deposits were also present. PRCC and MTSC both express CK7, AMACR, and EMA. However, absent expression of E-cadherin and strong CD10 expression favored PRCC. Multiple foci of solid spindle cells in a whorled pattern with clear cell change, necrosis, and high grade nuclei bordering on sarcomatoid RCC were present in other blocks. Multiple papillations and psammoma bodies also supported PRCC. A spectrum of spindle cell change was present, ranging from elongated tubules reminiscent of MTSC to whorled foci with high grade nuclei approaching sarcomatoid RCC. Results (if a Case Study enter NA) NA Conclusion Submission of multiple sections and awareness of the protean morphologic features of PRCC are essential in making the correct diagnosis.

CD10 expression in gastric adenocarcinoma and its correlation with histopathological features and lymph node metastasis

Background: Gastric cancer is one of the most common cancers worldwide. Invasion and metastasis are known prognostic factors. Previous studies have suggested CD10 expression in the epithelium and stroma of various carcinomas is associated with more aggressive behavior of the tumor. Aims and Objective: To study the immunohistochemical expression of CD10 in stromal cells of gastric adenocarcinoma and to correlate the expression with various clinicopathological features and lymph node metastasis. Materials and Methods: A cross sectional study of CD10 expression in 40 cases of gastric carcinoma in gastrectomy specimens was done. CD10 expression was correlated with age, gender, tumor site, tumor grade, histologic sub type, depth of invasion and lymph node status. Results: Out of 40 cases, 72.5% were males and 27.5% were females. Majority of cases were seen in 6th and 7th decades. Antrum was the most common location (70%) and intestinal morphology was the commonest histologic subtype (47.5%). Tumor size ranged from 2.5 to 11cms. 40% tumors were well differentiated. Majority (62.5%) of the tumors were in T3 stage. 25 (62.5%) cases showed a positive CD10 expression in stromal cells. Stromal CD10 expression in gastric carcinoma did not correlate with the age and gender of the cases as well as the location and size of the tumor, histologic subtype and lymph node involvement but correlated with depth of invasion (T stage) (p <0.05). Conclusion: CD10 expression in gastric adenocarcinoma shows a significant correlation with depth of invasion. CD10 may be used as an immunohistochemical surrogate of tumor behavior.

Prognostic Value of CD10 among Tunisian Patients with Nasopharyngeal Carcinoma

Introduction: CD10 expression was identified as a marker of poor prognosis in several types of cancer. However, its impact on the survival of Tunisian NPC patients has not been discussed. So, our objective was to confirm the prognostic value of this marker, in addition to its relationship to clinicopathologic parameters. Materials and Methods: Imunohistochemistry method was performed on formalin-fixed paraffin-embedded sections of 66 cases of NPC, 6 patients with inflammatory nasopharynx and 20 normal mucosa tissues. Results: CD10 expression was detected in 66.66 % of the NPC with predominant staining in stromal cells (81.81%). While, no expression of CD10 was noted in control group (inflammatory nasopharyngeal lesions and normal nasopharynx mucosa). CD10 positive cases were correlated with increasing tumor size (p=0.001) and lymph node metastasis (p=0.034). Furthermore, with the Kaplan-Meier test, a strong association was observed between the expression of CD10 and the recurrence status (p = 0.003). Multivariate Cox proportional hazard regression analysis showed that CD10 and lymph node metastasis factors were independent predictors of time to recurrence among NPC patients with respectively p=0.001 and p=0.044. Conclusion: The present study confirms the prognostic value of CD10 expression and suggests its strong effect on aggressive behavior of nasopharyngeal carcinoma.

Severe COVID-19 is characterised by inflammation and immature myeloid cells early in disease progression

SARS-CoV-2 infection causes a wide spectrum of disease severity. Immune changes associated with severe disease include pro-inflammatory cytokine production and expansion of immature myeloid populations. The relative importance of the immunological changes in driving progression to severe disease remain poorly understood. We aimed to identify and rank clinical and immunological features associated with progression to severe COVID-19. We sought to use tests available in an on-site diagnostic hospital laboratory to identify an immunological signature for severe disease development which could be detected prior to peak severity thereby allowing initiation of therapeutic interventions. We used univariate and multivariate analysis, including unbiased machine learning, to investigate the relationships between clinical and demographic characteristics, inflammatory markers, and leukocyte immunophenotypes with progression to severe disease in 108 patients and to rank these in importance. A combination of four features (elevated levels of interleukin-6 and C-reactive protein, coupled with reduced monocyte HLA-DR expression and reduced neutrophil CD10 expression), were strongly predictive of severe disease with an average prediction score of 0.925.

Expression of CD10 and CD15 in colorectal mucinous and signet ring adenocarcinomas and its relation to clinicopathological features and prognosis

BACKGROUND: CD10 and CD15 expression has been reported in several tumors. Whether CD10 and CD15 have a role in colorectal mucinous and signet ring adenocarcinoma (MSA) tumorigenesis is not yet known. OBJECTIVE: We aimed to investigate the role of CD10 and CD15 expression in mucinous colorectal adenoma-carcinoma sequence (ACS) and determine if there is any clinical and prognostic significance associated with their expression. METHODS: Seventy-five cases of colorectal MSA, and 9 cases of adenoma samples were collected. Manual TMA blocks were constructed and immunohistochemistry for CD10 and CD15 was done. RESULTS: Compared to adenomas, CD15 expression was significantly higher in MSA (p= 0.002), in contrast to CD10 expression. CD15 positivity was significantly associated with microsatellite stable (MSS) tumors (p= 0.018). The association between CD10 positivity and fungating tumor growth showed marginal significance. Unlike CD10, CD15 positivity showed significant association with overall survival of colorectal MSA patients. CONCLUSIONS: CD15 expression seems to have a role in mucinous colorectal ACS, with significant impact on the survival of MSA patients. Further studies are suggested to identify any genetic alterations that may underlie a potential association with disease progression.

Role of CD10 expression in endometriosis-associated mesenchymal stem cells on the progression of endometriosis-associated carcinoma.

5561 Background: Endometriosis-associated carcinomas (EACs) such as ovarian clear cell cancer (OCCC) are rare, aggressive, chemo-resistant malignancies. While endometriosis is a known chronic inflammatory condition, the molecular mechanisms for the malignant transformation of endometriosis is unknown. Mesenchymal stem cells (MSC) are a critical component of the ovarian cancer microenvironment. Cancer cells reprogram MSCs to form carcinoma-associated MSCs (CAMSCs), which promote cancer growth, chemotherapy resistance, and metastases. MSCs are also found within the endometriotic microenvironment. CD10, a surface protein expressed by endometrial stromal cells, is also expressed on endometriosis-associated MSCs (enMSCs). Preliminary data demonstrate CD10 expression is lost in a subset of enMSCs and this loss is correlated with the acquisition of tumor-promoting properties. We hypothesized that the CD10 negative subset of enMSCs behave similarly to CAMSCs and support the growth of OCCC. Methods: EnMSCs were isolated from primary human benign endometriosis deposits involving the ovary or fallopian tubes. Flow cytometry was used to measure surface CD10 expression. We investigated the role of low CD10 enMSCs versus high CD10 enMSCs on OCCC tumor cell growth, chemotherapy resistance and stem-like cell properties in vitro and tumor cell engraftment, growth, and metastases in vivo. Luciferase-expressing OCCC cells were (1) used alone, (2) mixed with low CD10 enMSCs, or (3) mixed with high CD10 enMSCs and injected orthotopically into the ovarian bursa of NSG mice. In vivo imaging system was used to follow tumor progression and metastasis. Results: Our results demonstrated that enMSCs have variable CD10 expression. EnMSCs with low CD10 expression significantly enhanced OCCC proliferation, resistance to cisplatin, and sphere formation compared to OCCC alone. In contrast, high CD10 expressing enMSCs significantly reduce OCCC proliferation and sphere formation. Interestingly, low CD10 enMSCs selectively enhanced OCCC cell growth and had no effect on high grade serious ovarian cancer cell growth. Moreover, a reduction of CD10 expression was observed over time when high CD10 enMSCs were co-cultured with OCCC cells. Our results also showed enhanced tumor engraftment when OCCC cells were co-injected with low CD10 enMSCs to 100% one week post-injection, compared to 40% with OCCC and high CD10 enMSCs and 60% with OCCC alone. Further, mice co-injected with low CD10 enMSCs demonstrated increased metastasis and decreased survival compared to mice co-injected with high CD10 enMSCs. Conclusions: Our results indicate there is a sub population of enMSCs, marked by decreased CD10 expression, which selectively enhances OCCC growth. This highlights the existence of a tumor-promoting stromal cell within endometriosis which may be critical to the formation and propagation of EACs.

Role of CALLA/CD10 Expression in Progression of Melanocytic Tumors: A Study in Egypt

BACKGROUND: Although most of melanocytic lesions can be diagnosed using morphology, there is a significant subset of lesions that are difficult to diagnose. These are a source of anxiety for patients, clinicians, and pathologists. This arouses the possible benefits of using ancillary techniques to solve this problem. CD10 is a zinc-dependent metalloproteinase, its expression is known to be associated with biological aggressiveness in various malignancies. AIM: This research observes the efficacy of CD10 in the progression of melanocytic tumors as well as the differential diagnosis between nevus and melanoma. METHODS: The material of this study included 49 paraffin blocks of Egyptian melanocytic tumors. CD10 expression either membranous and/or cytoplasmic in tumor cells was considered positive and scored, based on the percentage of cells stained and compared to Ki67 expression as a prognostic marker. RESULTS: In benign melanocytic nevi, only 16.7% of cases showed positive expression, all were + 1 score, compared to 82.6% of melanoma cases, mostly +1 score followed by +3 score and finally +2 score. The difference in CD10 expression among melanocytic tumors showed a highly statistically significant correlation between nevus and melanoma cases as well as in Spitz nevi versus other nevi. Another highly statistically significant correlation was observed between CD10 expression and both Ki67 expression and ulceration. CONCLUSION: CD10 expression was significantly higher expressed in melanomas rather than nevi with highly statistically significant positive relation with Ki67 and ulcer formation which supports its role as a potential biomarker in the development of malignant melanoma and marker of aggression.

SR-B1 and CD10 combined immunoprofile for differential diagnosis of metastatic clear cell renal cell carcinoma and clear cell carcinoma of the ovary

Both clear cell renal carcinoma (ccRCC) and clear cell carcinoma of the ovary (CCOC) have a clear cytoplasmic morphological feature, hence it is difficult to identify metastatic ccRCC and CCOC by morphology alone. At present, there are no effective immunohistochemical markers to distinguish between these two tumors. Studies have shown that the clear cytoplasm of ccRCC is mainly caused by cholesterol-rich lipids in the cytoplasm, while that of CCOC is due to the accumulation of cytoplasmic glycogen. Objective: to hypothesize that the scavenger receptor class B-type 1 (SR-B1) protein responsible for HDL cholesterol uptake may be differentially expressed in ccRCC and CCOC, and high CD10 expression in the renal tubular epithelium may assist in distinguishing between ccRCC and CCOC. Methods: effective immunohistochemical markers were applied in 90 cases of renal clear cell carcinoma and 31 cases of ovarian cancer to distinguish between the two types of tumors.Result: SR-B1 and CD10 expression is significantly higher in ccRCC than CCOC. Both SR-B1 and CD10 exhibited focal weak-medium intensity staining in CCOC, and their staining extent and intensity were significantly lower than ccRCC. The sensitivity and specificity of SR-B1 for identifying ccRCC were 74.4% and 83.9%, respectively. The sensitivity and specificity of CD10 for identifying CCOC were 93.3% and 80.6%, respectively. The combined SR-B1( +) CD10( +) immunoprofile supports the diagnosis of ccRCC with a specificity of 93.5%. The combined SR-B1(-) CD10(-) immunoprofile supports the diagnosis of CCOC with a specificity of 93.3%. Conclusions: our findings demonstrate that the combination of SR-B1 and CD10 immunoprofiling is a valuable tool for differential diagnosis of ccRCC and CCOC.