Comment on "Clinical and Pathological Features of Early-Stage Metaplastic Carcinoma and Associated Patient Outcomes".

O059 / #244Topic:AS16 - Lupus Nephritis-PathogenesisABSTRACT CONCURRENT SESSION 10: INTEGRATING PROTEOMIC & TRANSCRIPTOMICS IN SLE24-05-2025 10:40 AM - 11:40 AMBackground/PurposeTreatment response in lupus nephritis (LN) remain inadequately low, highlighting the need for better understanding of LN pathogenesis to improve management. Single-cell transcriptomic studies are providing an unprecedented catalog of cell states in LN, yet their spatial organization is not well understood. Since structure underlies function, we aim to map the spatial organization of immune cells in LN.MethodsWe developed a serial immunohistochemistry (sIHC) workflow (18-plex), followed by imaging and destaining cycles. Image processing was performed using HALO (Indica Labs), including AI-assisted tissue classification. PCA was used for dimensional reduction, and KNN and SNN algorithms were applied to identify immune cell types based on their markers’ fluorescent intensity. Immune cell aggregates in the tissues were defined using DBSCAN as a minimum of 3 cells within a radius (epsilon) of 50 μm to infer interactions between cells. Aggregate sizes were categorized into small (3-29 cells), medium (30-99 cells), and large (>100 cells) based on the frequency distribution (Figure 1A,B). The proportion of immune cell types in each aggregate was used for K-means clustering to determine aggregate subtypes. Clinical features were correlated with each aggregate subtype using Pearson’s correlation coefficient (Figure 2).Figure 1.Demographics of intrarenal immune cell aggregates. (A) Digitalized biopsy showing an example of the distribution of immune cells in LN. (B) Examples of intrarenal immune cell aggregates of different sizes. (C) Distribution of aggregates by size and by total cells. (D) Distribution of aggregates by size and region. (E) Density of aggregate types according to size and class.Figure 2.Correlation between aggregate subtypes and clinical features. Left heatmaps show aggregates subtypes. Middle heatmaps display the average density of aggregate subtypes (average number of aggregates/mm²). Right heatmaps show the correlation matrices between the aggregate subtypes and clinical features. (A) Glomerular small aggregate (B) Tubulointerstitial small aggregate (C) Tubulointerstitial medium aggregate (D) Tubulointerstitial large aggregate. Act: NIH activity index; Chr: NIH Chronicity Index.ResultsIn this analysis, we included 29 kidney biopsies of LN resulting in 1,913,845 cells (182,783 immune cells). We identified 12,371 cellular aggregates. Most (97%) aggregates were small (<30 cells) (Figure 1C,D); however, medium and large aggregates included 33.7% of immune cells. Glomerular aggregates were numerically increased in proliferative and mixed classes (Figure 1E). These were small and primarily composed of CD68+ myeloid cells (Figure 2A). Glomerular aggregates rich in CD68+ cells negatively correlated with UPCR, while aggregates rich in lymphocytes negatively correlated with chronicity (Figure 2A). In contrast, tubulointerstitial (TI) aggregate density was similar across LN classes (Figure 1E) and negatively correlated with GFR. Significant heterogeneity in aggregate composition revealed >10 aggregate subtypes according to composition and size (Figure 2). Small aggregates tended to be restricted to 1-2 cell types each, while medium and large aggregates included mixed proportions of CD4+ T, CD8+ T, B, dendritic, myeloid, and plasma cells, suggesting germinal center-like structures (Figure 2). Distinct TI aggregate subtypes associated with specific clinical and pathological features (Figure 2B,C).ConclusionsWe describe the heterogeneity in glomerular and TI immune cell structures in LN, offering insights into LN pathological processes and potential cellular interactions based on proximity. TI inflammation appears similar in membranous and proliferative LN, yet specific immune structures are linked to distinct clinical and pathological features.

The purpose of this study was to evaluate the incidence of local recurrences (LRs) and second primary tumors (SPTs) from squamous cell carcinoma (SCC) of the oral cavity primarily treated with surgery and to further study their relationship with several primary tumor clinical and pathological features. Five hundred of 522 patients with SCC of the oral cavity primarily treated with surgery were retrospectively analyzed for the appearance of LRs and SPTs within the oral cavity. All patients with SPTs fulfilled the Warren & Gates criteria. Several clinical features were analyzed. Histological study included TNM classification, tumor size, tumor thickness, surgical margins, perineural infiltration, peritumoral inflammation, and bone involvement. In the univariant analysis, the possible association between different clinical and pathological features and the presence of LRs or SPTs was analyzed by means of the chi-square test for categorical data and the Student's t test for parametric data. The appearance of LRs and SPTs was also studied by binary logistic regression as time-dependant phenomena, in the univariant analysis. Logistic regression was also used for the multivariant analysis between the selected variables. The Kaplan-Meier method was used to estimate the probability of SPT- or LR-free survival. The mean duration of the follow-up period was 52.27 +/- 49.52 months. At the end of this time, 53.82% of the patients were alive without evidence of disease, whereas 31.48% had specifically died of disease. Twenty-eight (5.6%) patients developed an SPT within the oral cavity, whereas 95 (19%) patients developed an LR during the whole follow-up period. The 5-year disease-specific survival rate for the whole series was 67.2%, in contrast to 34.9% in the group of patients with SPT and/or LR. In relation to the univariant analysis, T classification, TNM staging, pT classification, surgical margins, bone involvement, and postoperative radiotherapy (RT) were found to be predictive for LR. In relation to the multivariant analysis, only postoperative RT and bone involvement were predictive for the development of LR. The identification of preoperative and postoperative clinical and pathological features that prelude a higher risk for the appearance of LRs and/or SPTs may be of potential interest in determining which patients should benefit of a closer regular follow-up. When considering together the whole clinical and pathological features, only postoperative RT and bone involvement were predictive for the development of LRs. Because of the poor survival rate of the affected patients, we strongly recommend aggressive surgical treatment following the appearance of an SPT or LR.

Clinical Characteristics and Survival Outcomes of Metaplastic Breast Carcinoma Subtypes: A Retrospective Study.

BackgroundPalpable ductal carcinoma in-situ (pDCIS) is a subset of DCIS presenting with a clinical mass. We hypothesized pDCIS would have more aggressive clinical and pathological features, and higher rates of recurrence and upgrade to invasive disease compared to screen-detected DCIS. Materials and methodsWe performed a retrospective analysis of female patients (age 28–76) with DCIS on core-needle biopsy. pDCIS patients had a physician documented palpable mass prior to initial biopsy. Descriptive statistics were performed to compare groups. ResultsThis study included 83 patients, 26 had pDCIS and 57 had screen-detected DCIS. Mean duration of follow-up was 49.4 months. pDCIS patients had significantly larger lesions (p = 0.03) which were more frequently biopsied via ultrasound (p = 0.002). In multivariate analysis, pDCIS was associated with ultrasound guided core needle biopsy, size of DCIS >2 cm, and comedo pattern (p = 0.001, p = 0.007 and p = 0.022, respectively). 7.7 % of pDCIS cases versus 3.5 % of screen-detected cases were upgraded to invasive cancer (p = 0.59). There was no difference in local recurrence (p = 0.55) between groups. Neither group experienced regional or distant recurrence. ConclusionspDCIS was associated with some aggressive pathologic and clinical features and was more frequently diagnosed by ultrasound guided core-needle biopsy than screen-detected DCIS. However, there was no significant difference in rate of recurrence or upgrade to invasive disease between groups. Key messageAlthough pDCIS was associated with some aggressive pathologic and clinical features, there was no significant difference in rate of recurrence or upgrade to invasive disease compared to screen-detected DCIS.

Molecular Features of Germinal Cell Derived B-Cell Lymphomas Using miRNA Signatures

To explore the categories of drugs causing hepatotoxicity and analyze the clinical and histological features of the corresponding drug-induced liver injury (DILI), in order to gain insights into potential diagnostic factors for DILI. A total of 138 DILI patients treated at our hospital from April 2008 to April 2010 were retrospectively analyzed. The responsible drug for each DILI case was recorded. The Roussel Uclaf Causality Assessment Method (RUCAM) had been used to diagnose DILI. Only cases that had scored as highly probable or probable (more than or equal to 6 points by RUCAM) were included in this study. The patients' general condition, clinical manifestations, and serum biochemical and immunological parameters were assessed. Sixty-six of the patients underwent liver biopsy, and were assessed for liver pathological changes. Clinical and laboratory test data were collected and used to classify the total 138 cases as hepatocellular injury, cholestatic, or mixed hepatocellular-cholestatic types. Within our patient population, the leading cause of DILI was Chinese herb medicine, accounting for 53.62% of cases. Antibiotics were implicated in 7.97% of cases, and dietary supplement in 6.52% of cases. Correlation between the clinical features and histological injury pattern was stronger at the time of biopsy (more than or equal to 3 days after laboratory results) (kappa = 0.63, P less than 0.05) than at the onset of DILI (kappa = 0.25, P less than 0.05). All modified hepatic activity index (HAI) necroinflammatory scores and fibrosis scores were more severe in the cholestatic and mixed injury types than in the hepatocellular injury type (P less than 0.01 and P less than 0.05, respectively). Chinese herbal medicine, dietary supplements and antibiotics were the main causes of DILI in our patient population. The clinical and histological features correlated well, especially at later stages of DILI. The degree of inflammation and fibrosis was significantly higher in cholestatic and mixed hepatocellular-cholestatic injury types than in the hepatocellular injury type. Assessment of both clinical and pathological features may represent a more accurate diagnostic method for DILI.

Metaplastic carcinoma is a rare form of breast cancer. It constitutes a distinct aggressive form of invasive breast cancer with histological evidence of epithelial to mesenchymal transition towards spindle, chondroid or osseous cell type. Osseous metaplasia is an exceptionally rare component in metaplastic breast carcinoma. We present a case of 40 yr old female who was diagnosed with Metaplastic carcinoma of breast on fine needle aspiration cytology (FNAC) and subsequently confirmed by histopathological examination. The patient reported to our institution with complaints of painless left breast lump of 5 yr duration. USG findings revealed large infiltrative hypoechoic mass in left upper quadrant of breast suggestive of malignancy. FNAC of lump showed loosely cohesive clusters of malignant spindle cells along with multinucleated giant cell in background of chondroid stroma. A tentative diagnosis of metaplastic carcinoma breast was made. Modified radical mastectomy was performed. Histopathological examination of specimen revealed presence of osteoid lined by malignant osteoblasts like cells interspersed with multinucleated giant cells. A diagnosis of metaplastic carcinoma of breast with osteosarcomatous differentiation was confirmed on histopathological examination. Metaplastic breast carcinoma are heterogenous group of tumors constituting 0.2% of breast carcinomas. Age group and clinical features and radiographic features are similar to other invasive breast carcinomas. Cases is presented for its rarity and utility of FNAC in diagnosing such cases having divergent histological features.

Metaplastic breast carcinoma (MBC) is a distinct invasive breast carcinoma. It is a rare and heterogeneous group of malignancies, generally characterized by hormone receptor and human epidermal growth factor receptor 2 (HER2) negativity. The aim of the study is to evaluate epidemiological aspects, clinical characteristics, pathological features and biological profile of MBC cases diagnosed in our institution. All patients with MBC diagnosed and treated in our institution between January 2004 and June 2009 were included. Twelve patients were identified. The median age was 46.5 (range 35-57 years) and the average tumor size was 6.9 cm (3.5-18 cm). Seven cases were purely squamous cell carcinomas, one was an adenosquamous carcinoma and four cases were mixed epithelial and mesenchymal metaplastic carcinomas. Primary treatment was mastectomy in 11 patients and wide local excision in one patient. There was lymph node (LN) involvement in four patients. Three patients were stage IIA, eight were stage III (2 IIIA, 6 IIIB), and one was stage IV. Estrogen and progesterone receptors status and over expression of HER2 were assessed. Eleven tumors had a basal-like phenotype and one tumor had luminal B phenotype. This study found a high incidence of MBC compared to Western countries. The tumors occur at an earlier age of onset and are usually diagnosed at a late stage with predominance of squamous cell carcinoma subtype. LN metastases are found in the third case and the tumors are most often basal-like phenotype significantly reducing therapeutic options.

Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia.

Objective To investigate the clinicopathologic and immunohistochemical characteristics of breast carcinosarcoma with osteosarcoma components and its differential diagnosis. Methods The pathologic features and clinical manifestations of the two patients were retrospectively reviewed. Immunohistochemistry was performed and the literature was reviewed. Results Histopathologically, the neoplasm consisted of invasive ductal carcinoma of no special type and poorly ( case 1 ) or well (case 2) differentiated osteosarcomatoid elements. The morphological transition from carcinoma to sarcomatoid elements was seen. Immunohistochemically,the carcinoma cells were positive for CK and EMA , the sarcomatoid elements were stained positive for vimentin, and a few cells of two elements were positive for S-100 protein. Ki-67 and VEGF were over expressed in both elements of Case 1.In case2 Ki-67 expression was low in both elements and VEGF over expression was only seen in sarcomatoid elements. Some of the carcinoma cells were positive for ER. Conclusions Carcinosarcoma of the breast with osteosarcomatoid elements is a rare type of mixed epithelial/mesenchymal metaplastic breast carcinoma. The types and proportion of carcinoma and sarcomatoid elements determine the diagnosis. Key words: Breast neoplasm; Metaplastic carcinoma; Carcinosarcom; Immunohistochemistry

Triple-negative breast cancers are known collectively to demonstrate a more aggressive clinical course and earlier recurrence than cancers of other histological subtypes. However, the literature on rare triple-negative breast cancers and the association of histological type with survival and risk of metastasis is sparse. To present the clinical and demographic characteristics, treatment patterns, and overall survival (OS) for histologically rare (<10% of breast cancers) triple-negative breast cancer types: medullary carcinoma, adenoid cystic carcinoma, and metaplastic breast carcinoma. This cohort study was performed in the US using data reported by the National Cancer Database between 2010 and 2016. Confirmed cases of medullary carcinoma, adenoid cystic carcinoma, and metaplastic breast cancer were analyzed. Univariable analyses and multivariable Cox regression models were performed. Data analysis was performed from April to May 2020. The primary outcome was 5-year OS. Secondary outcomes included site of metastasis, effect of immunohistochemistry, management, and 2-year mortality. A total of 8479 patients with breast cancer (mean [SD] age; 62.6 [14.3] years; 8435 women [99.48%]) were analyzed. Metaplastic carcinoma was the most commonly diagnosed histological type in this cohort, with 6867 patients (81%), followed by 1357 (16%) with adenoid cystic carcinoma and only 255 (3%) with medullary carcinoma. Medullary carcinoma presented earlier in life, at a median (interquartile range) age of 53 (45-62) years, compared with 62 (53-72) years for patients with adenoid cystic carcinoma and 63 (52-74) years for patients with metaplastic carcinoma. The proportion of tumors with triple-negative immunohistochemistry varied by histological type for medullary carcinoma (57 patients [22.4%]), adenoid cystic carcinoma (653 patients [48.1%]), and metaplastic carcinoma (3637 patients [53.0%]). Patients with adenoid cystic carcinoma were less likely to receive radiotherapy (711 patients [52.4%]) and chemotherapy (175 patients [12.9%]) compared with patients with medullary carcinoma (radiotherapy, 156 patients [61.2%]; chemotherapy, 190 patients [74.5%]) and metaplastic carcinoma (radiotherapy, 3416 patients [49.7%]; chemotherapy, 4709 patients [68.6%]). The 5-year OS rate was superior for patients with medullary (91.7%) and adenoid cystic carcinoma (88.4%) compared with patients with metaplastic carcinoma (63.1%). The 5-year mortality rate for adenoid cystic carcinoma was 8.33% vs 36.91% for metaplastic carcinoma. Nationally, over the course of 7 years, medullary carcinoma was most common and metaplastic carcinoma had the worst 5-year OS among the rare histological breast cancer subtypes analyzed. Factors associated with a poor prognosis for metaplastic carcinoma included advanced stage, lung metastasis, older age, and not receiving chemotherapy or radiation therapy. Future research focusing on rare subtypes of breast cancer is desirable and could inform the optimal management of these relatively understudied carcinomas.

Objective To study the clinical pathological features between the subtypes of the female mucinous breast cancer with its prognosis. Methods Eighteen cases confirmed as pure mucinous breast cancer (PMBC) with complete case report and follow-up information in Beijing Shijitan Hospital was collected and divided into type A PMBC and type B PMBC. A retrospective analysis was performed for both groups on clinical and pathological features and prognosis. Results The axillary metastasis rate for type A PMBC was 13.3%, and 0 for type B PMBC. The distant metastasis rate for type A was 6.7%, and 0 for type B. The percentage of ER and PR positive cases for type A was 93.3% and 86.7%, respectively, and was both 33.3% for type B. The HER-2 gene overexpression rate was both 0 for type A and B. And for Ki-67 expression, the low and high expression rate for type A was 80.0% and 20.0%, respectively, and was 100.0% and 0 for type B, respectively. Conclusions PMBC is a special subtype of the breast cancer with good prognosis. The pathological features and biological behavior between type A and type B is different. Further research and more data will be needed to access the prognosis with the classification. Key words: Breast neoplasms; Pure mucinous breast cancer; Clinical features; Prognosis

Rarely, patchy right colonic inflammation has been observed in patients with left sided chronic ulcerative colitis (CUC), but the clinical significance of this finding is unknown. Therefore, the aim of this study was to evaluate the clinical and pathologic features and natural history of CUC patients with left-sided colitis combined with patchy right colonic inflammation and to compare the clinical course to a control group of patients with isolated left-sided CUC. Twelve patients with clinically and pathologically confirmed left-sided CUC, but also with patchy right colonic inflammation, were identified from a cohort of 352 consecutive patients with CUC who underwent colonoscopy at the Brigham and Women's Hospital between 1996 and 2000. In this cohort, 127 patients had left-sided colitis. As the first study to use controls in this setting, 35 consecutive patients with left-sided CUC, but without patchy right colonic inflammation, were selected and evaluated during the same time period. In all patients, the medical records were reviewed for a wide variety of clinical, endoscopic, and pathologic features. The mean follow-up time for the study and control groups was 105 +/- 128 and 112 +/- 80 months, respectively. Patients in the study group were significantly older than the control group at the time of diagnosis (47 +/- 17 years vs 35 +/- 14 years, p = 0.048), but the two groups had a similar gender distribution (25% male vs 40% male), prevalence of extraintestinal manifestations (25% vs 11%), frequency of nonsteroidal anti-inflammatory drug use (75% vs 50%), family history of colitis (27% vs 15%), current tobacco use (8% vs 3%), history of appendectomy (8% vs 0%), and overall severity of disease (33% vs 46%). None of the patients in the study group, and only one control patient, had disease progression to pancolitis. One study patient developed high-grade dysplasia in the rectum that required a colectomy. None of the study or control patients developed clinical or pathologic features of Crohn's disease. Rarely patients with left-sided CUC may have patchy right colonic inflammation. The clinical features and natural history of patients with left-sided CUC and patchy right colonic inflammation is similar to patients with isolated left-sided CUC.

Aim:To characterise the clinical and pathological features of 24 patients with biopsy proven Idiopathic Orbital Inflammatory Syndrome (IOIS).Methods:Retrospective case series.Results:The study included 14 men and 10 female patients, ranging in...

Pediatric-type follicular lymphoma (PTFL) and pediatric nodal marginal zone lymphoma (PNMZL) are rare pediatric-type indolent B-cell lymphomas (PedIBCL) that differ clinicopathologically from their adult counterparts. Accurate diagnosis is important to avoid overtreatment but is often challenging. The mutational landscape of PTFL is known and may aid diagnosis, but the genetic features of PNMZL are not well understood. We analyzed 21 cases of PedIBCL according to their clinicopathologic findings and classified them into PTFL (n=11), PNMZL (n=2), and “mixed type” tumors (n=8) showing ambiguous histology. We also analyzed 2 cases of adult B-cell lymphomas showing features of PedIBCL. Targeted sequencing of 121 lymphoma-related genes was performed. The median age of PedIBCL patients was 16 years (range: 3 to 47), and all but 1 PTFL patient were male. All patients presented with limited-stage disease, and only 1 relapsed. There were no significant differences in clinical features among the 3 PedIBCL groups. The most frequently mutated genes were MAP2K1, TNFRSF14, KMT2C, IRF8, and NOTCH2. The genetic features of all groups were similar to the established mutational landscape of PTFL. The 2 adult B-cell lymphomas cases also had MAP2K1, TNFRSF14, and IRF8 mutations, but the clinical features were not typical of PedIBCL. In summary, this study demonstrated that PTFL and PNMZL are similar diseases with overlapping clinical, pathologic, and genetic features; mixed type tumors can also occur. Atypical adult cases with similar histologic features were also observed. Therefore, the disease spectrum of PedIBCL may be much broader than is currently believed.