[Malignant peripheral nerve sheath tumor: a clinicopathological analysis].

Objective: To investigate the clinicopathological, immunophenotypic, and genetic features of malignant peripheral nerve sheath tumor (MPNST). Methods: Twenty-three cases of MPNST were diagnosed at the Jiangsu Province Hospital (the First Affiliated Hospital of Nanjing Medical University), China, between January 2012 and December 2022 and thus included in the study. EnVision immunostaining and next-generation sequencing (NGS) were used to examine their immunophenotypical characteristics and genomic aberrations, respectively. Results: There were 10 males and 13 females, with an age range of 11 to 79 years (median 36 years), including 14 cases of neurofibromatosis type I-associated MPNST and 9 cases of sporadic MPNST. The tumors were located in extremities (7 cases), trunk (4 cases), neck and shoulder (3 cases), chest cavity (3 cases), paraspinal area (2 cases), abdominal cavity (2 cases), retroperitoneum (1 case), and pelvic cavity (1 case). Morphologically, the tumors were composed of dense spindle cells arranged in fascicles. Periphery neurofibroma-like pattern was found in 73.9% (17/23) of the cases. Under low magnification, alternating hypercellular and hypocellular areas resembled marbled appearance. Under high power, the tumor cell nuclei were irregular, presenting with oval, conical, comma-like, bullet-like or wavy contour. In 7 cases, the tumor cells demonstrated marked cytological pleomorphism and rare giant tumor cells. The mitotic figures were commonly not less than 3/10 HPF, and geographic necrosis was often noted. Immunohistochemically, tumor cells were positive for S-100 (14/23, 60.9%) and SOX10 (11/23, 47.8%). The loss of the CD34-positive fibroblastic network encountered in neurofibromas was observed in 14/17 of the MPNST cases. The loss of H3K27me3 expression was observed in 82.6% (19/23) of the cases. Moreover, SDHA and SDHB losses were presented in one case. NGS revealed that NF1 gene loss of function (germline or somatic) were found in all 5 cases tested. Furthermore, four cases accompanied with somatic mutations of SUZ12 gene and half of them had somatic mutations of TP53 gene, while one case with germline mutation in SDHA gene and somatic mutations in FAT1, BRAF, and KRAS genes. Available clinical follow-up was obtained in 19 cases and ranged from 1 to 67 months. Four patients died of the disease, all of whom had the clinical history of neurofibromatosis type Ⅰ. Conclusions: MPNST is difficult to be differentiated from a variety of spindle cell tumors due to its wide spectrum of histological morphology and complex genetic changes. H3K27me3 is a useful diagnostic marker, while the loss of CD34 positive fibroblastic network can also be a diagnostic feature of MPNST. NF1 gene inactivation mutations and complete loss of PRC2 activity are the common molecular diagnostic features, but other less commonly recurred genomic aberrations might also contribute to the MPNST pathogenesis.

[Chronic active Epstein-Barr virus infection in the gastrointestinal tract: a clinicopathological study of three cases].

Objective: To study the clinicopathological features of chronic active Epstein-Barr virus infection (CAEBV) in the digestive tract and to discuss its differential diagnosis. Methods: The clinical data of 3 cases of CAEBV in the digestive tract diagnosed in Jiangsu Province Hospital (the First Affiliated Hospital of Nanjing Medical University), Nanjing, China from December 2018 to August 2020 were collected. Three cases of CAEBV were evaluated using histology, immunohistochemistry and in situ hybridization. The related literature was reviewed. Results: Three patients were all males, aged 33, 32 and 31 years, respectively. All patients had a history of intermittent fever and repeated diarrhea for the past years with persistent increase in EB viral load (DNA copies) in peripheral blood. Endoscopically, intestinal tract was involved in all cases with ulcers, and esophagus was involved concurrently in 1 case showing nodular lesions. Microscopically, there were moderate polymorphic inflammatory infiltrate with lymphoid component displaying no or mild atypia in all cases and deep fissuring ulcers in one case (case 3). All tumor cells were positive for CD3 and TIA-1, and negative for CD56 and CD5. Cases 1 and 2 showed CD4-/CD8-, whereas case 3 displayed CD4+/CD8-. In situ hybridization for Epstein-Barr virus-encoded RNA was positive in all 3 cases. Follow-up data showed that cases 1 and 2 were free of disease progression at the end of follow-up (16 months and 17 months, respectively). However, case 3 progressed to extranodal NK/T-cell lymphoma 22 months after the initial diagnosis. Conclusions: CAEBV of the digestive tract is a rare lymphoid proliferative disorder with potential transformation to extranodal NK/T-cell lymphoma. It is a great mimicker of inflammatory bowel disease, especially in small biopsy specimens. It is important to integrate clinicopathological, radiological and laboratory data to avoid misdiagnosis.

[Clinicopathological features of ectopic meningothelial hamartoma].

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of ectopic meningothelial hamartoma (EMH). Methods: Three cases of EMH diagnosed in the First Affiliated Hospital of Nanjing Medical University from January 2014 to December 2020 were enrolled. All cases were evaluated by clinical and imaging features, HE and immunohistochemical staining, and the relevant literature was reviewed. Results: There were one male and two female patients, aged 2, 67 and 19 years, respectively. Clinically, they presented as skin masses in the head and face region (two cases) and sacro-coccygeal region (one case). Grossly, the lesions ranged in size from 1.6 cm to 8.9 cm. Microscopically, the lesions were ill-defined, and located in the dermis and subcutis, and showed pseudovascular channels lined by monolayer of cuboidal to flattened epithelium with mild atypia, with variable cystic cavity formation. There was prominent interstitial fibrosis. Concentric, lamellated, onion skin-like arrangement with short spindle or ovoid cells and psammoma bodies were noted. Immunohistochemically, these cells were strongly positive for SSTR2, EMA, vimentin and progesterone receptor. Ki-67 positive index was low, approximately 1%. Conclusions: EMH is uncommon. Definitive diagnosis relies on histopathologic examination. The importance in recognizing the lesions is to differentiate from other more aggressive tumors.

[Correlation of VISTA and PD-L1 expression with the clinicopathological features and prognosis in triple-negative breast cancer].

Objective: To investigate the expression of VISTA and PD-L1 in triple-negative breast cancer (TNBC) and to explore its relationship with clinicopathologic features and prognosis. Methods: Ninety TNBC patients who underwent surgical resections between 2016 to 2018 in Jiangsu Province Hospital were selected. The expression of VISTA and PD-L1 in both tumor cells and immune cells was evaluated by immunohistochemistry, and the relationship with clinicopathologic parameters and prognosis was analyzed. Results: VISTA was expressed in 17.8% (16/90) of the tumors. The expression of VISTA in tumor cells was related to a higher Ki-67 proliferation index (P=0.02) and higher number of tumor-infiltrating lymphocytes (TIL, P<0.01). VISTA was expressed in 71.1% (64/90) of the immune cells and the expression correlated with smaller tumor size (P=0.02), lower T stage (P=0.04), higher number of TIL (P<0.01), higher number of CD8+T cells (P=0.03) and higher Ki-67 proliferation index (P=0.02). PD-L1 was expressed in 17.8% (16/90) of the immune cells and the expression correlated with higher histologic grade (P=0.04), higher Ki-67 proliferation index (P=0.02) and higher number of TIL (P<0.01). VISTA expression was higher in immune cells within TNBC patients than PD-L1 (P<0.01). Among 90 TNBC patients, complete follow-up was obtained in 85 patients, 8 of whom had recurrences or metastasis after surgery, and two patients cases died of recurrences or metastasis. Conclusions: The expression rate of VISTA is higher than that of PD-L1 in TNBC. The expression of VISTA in immune cells predicts a lower T stage. VISTA may act as an effective immunotherapy target.

[CIC-rearranged sarcoma with rhabdoid features: a clinicopathological analysis].

Objective: To investigate the histopathologic, immunohistochemical, molecular genetic characteristics of CIC-rearranged sarcoma (CRS) with rhabdoid features. Methods: The clinical and pathologic data of two cases of CRS diagnosed between 2019 and 2021 at the Department of Pathology, Jiangsu Province Hospital were analyzed. Immunohistochemical study and fluorescence in situ hybridization (FISH) were performed. The relevant literature was reviewed. Results: Both patients were female, one was 58 years old, with tumor located in left thigh; the other was 43 years old, with tumor located in left pelvic cavity. Microscopically, both tumors were composed of small to medium-sized round, oval cells, arranged in nodules or sheets. The tumor cells showed irregular nuclear outline, coarse chromatin with prominent nucleoli and brisk mitotic activity. Both cases showed rhabdoid phenotype with myxoid stromal changes. Immunohistochemically, both cases were positive for CD99 and c-myc. High WT1 reactivity was seen in classic area, with low reactivity in rhabdoid area. There was no INI1 lost in both cases. Both were negative for NKX2.2 and NKX3.1. By FISH both cases demonstrated convincing break-apart signals of CIC gene. One patient died of disease after 1 month, and the other died of disease after 3 months. Conclusions: CRS is a small round cell undifferentiated sarcoma of the bone and soft tissue defined by molecular genetic characteristics, and may show atypical morphologic and immunophenotypic characteristics such as rhabdoid features. A correct understanding of its rare morphologic and immunophenotypic characteristics, combined with molecular pathologic detection, is conducive to correct diagnosis.

[Changes of immunohistochemical biomarkers before and after neoadjuvant chemotherapy in breast cancer and their prognosis].

Objective: To investigate changes in the expression of immunohistochemical (IHC) markers and factors associated with the effect of chemotherapy before and after neoadjuvant chemotherapy (NAC). Methods: A retrospective study included 200 breast cancer patients treated with NAC between January 2016 and December 2018. We analyzed the changes in the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 in pre- and post-treated samples and the predictive factors of NAC. Results: Among the 200 cases, 16 cases were luminal A, 108 cases were luminal B, 36 cases were HER2+subtype, and 40 cases were basal-like. Twenty-five patients (12.50%) achieved pathological complete remission (PCR).There were significant differences in PR and Ki-67 before and after NAC but there were no differences in ER and HER2.In univariate analysis, factors associated with PCR were tumor less than 5 cm(P=0.009), non-luminal breast cancer (P=0.001), ER negative(P=0.001), PR negative (P=0.029) and HER2 positive(P=0.001). Tumor less than 5 cm [P=0.020, OR=2.581, 95%CI (1.207, 5.753)], ER negative [P=0.011, OR=2.264, 95%CI (1.207, 4.248)] and HER2 positive[P=0.007, OR=2.412, 95%CI (1.275, 4.561)] remained predictive variables in multivariate analysis after correction for the other variables. Conclusions: The expression of Ki-67 decreases after NAC. Negative PR and ER and positive HER2 status are related to the efficacy of pCR for breast cancer, and have guiding significance for the prognosis evaluation of NAC.

[Epithelioid hemangioendothelioma with TFE3 translocation in soft tissue:a clinicopathological study].

Objective: To investigate the clinicopathological and molecular features, diagnosis and differential diagnosis of TFE3-rearranged epithelioid hemangioendothelioma (EHE). Methods Two cases of TFE3-rearranged EHE arising from soft tissues, diagnosed by the Pathology Department of the First Affiliated Hospital of Nanjing Medical University from 2013 to 2020 were observed. EnVision method was used for immunophenotyping, fluorescence in situ hybridization (FISH) was used to test TFE3 gene rearrangements and WWTR1-CAMTA1 fusion gene,and next-generation sequencing (NGS) was used to delineate the fusion transcripts. Results: Details of these two cases were as follows: case 1, male, 51 years old, with tumor in the right temporal region; case 2, female, 42 years old, with tumor in the right neck. The tumors showed progressive painless enlargement. Grossly, the tumor of case 1 was multinodular with unclear boundary and grayish red cut surface, while the tumor of case 2, originating from a vein, appeared as a firm, tan mass within vessel wall. Microscopically, both tumors showed moderate cellularity and were consisted of plump, epithelioid, or histiocytoid cells with eosinophilic cytoplasm and mild-to-moderate nuclear pleomorphism. Most of the tumor cells were arranged in solid or alveolar growth patterns, while some tumor cells showed intraluminal papillary growth pattern in case 1 and anastomosing vascular channels and extramedullary hematopoiesis in case 2. Immunohistochemically, the tumor cells showed diffuse positivity for CD31, CD34, ERG, and TFE3. FISH revealed TFE3 break-apart signals in two cases, but WWTR1-CAMTA1 gene fusion was not detected. NGS identified YAP1 (exon1)-TFE3 (exon6) fusion gene in case 2. Clinical follow-up information was available in both cases for a follow-up period of 15 and 59 months respectively. Patient 1 had a relapse 22 months after surgery, and was currently alive with the tumor. Patient 2 remained disease-free. Conclusions: TFE3-rearranged EHE is a rare molecular subtype of EHE, with accompanying characteristic morphologic features. However the morphologic spectrum remains under-recognized, and more experience is needed. Immunohistochemical and molecular examinations are helpful for the diagnosis and differential diagnosis of the disease.

[Clinicopathological features of inflammatory myofibroblastic tumor].

Objective: To investigate the clinicopathological diagnosis and differential diagnosis of inflammatory myofibroblastic tumor (IMT). Methods: Thirty-two cases of IMT collected at the People's Hospital of Jiangsu Province from May 2010 to May 2020 were evaluated for their clinical, histologic, immunohistochemical and genomic features, and relevant literature was reviewed. Results: There were 19 male and 13 female patients, with age ranging from 5 to 65 years (mean, 37 years). The tumors were located in the lung and mediastinum (10 cases), gastrointestinal tract and mesentery/omentum (12 cases), urinary bladder (5 cases), head and neck (3 cases), somatic soft tissue (1 case), and retroperitoneum (1 case). Four cases of epithelioid inflammatory myofibroblastic sarcoma (EIMS) were all located intra-abdominally. Histologically, the tumor cells were myofibroblasts and fibroblasts arranged in predominantly fusiform pattern, with variably edematous to myxoid background or sclerotic collagenized stroma, and variably mixed chronic or acute inflammatory cells infiltration. EIMS were composed mainly of epithelioid tumor cells, with myxoid stroma and numerous neutrophils. Immunohistochemically, the tumor cells expressed cytoplasmic ALK (25/32, 78%), whereas the four EIMS showed nuclear membrane ALK staining pattern. The tumor cells also expressed CKpan (8/19), SMA (24/32, 75%) and desmin (12/32, 38%); all four EIMS also showed strong positivity for desmin. Fluorescence in situ hybridization (FISH) for ALK gene rearrangement showed split apart signals in 12 of 15 cases, most commonly with atypical signals. Next-generation sequencing (NGS) was performed in three tumors and showed that one case of lower leg IMT harbored a novel CLIP2-ALK fusion, and two cases of EIMS harbored RANBP2-ALK fusion. Follow-up data were available in 29 patients. Twenty-two patients were alive with no evidence of tumor, four patients had tumor recurrences (three patients were treated with crizotinib and were alive with tumor), and three patients died of the disease (including two patients with EIMS). Conclusions: IMTs show a wide morphologic spectrum, and should be differentiated form a variety of benign or malignant tumors. Immunohistochemistry (ALKp80, ALKD5F3) and FISH (ALK break-apart probe) could assist the diagnosis of IMT, with NGS recommended for the atypical cases.

[Clinicopathological study of large B-cell lymphoma with IRF4 rearrangement].

Objective: To study the clinicopathological features of large B-cell lymphoma (LBCL) with IRF4 rearrangement. Methods: Seven cases of LBCL with IRF4 rearrangement collected at the First Affiliated Hospital of Nanjing Medical University from November 2018 to October 2019 were evaluated by hematoxylin and eosin staining, immunohistochemistry and fluorescence in situ hybridization detection. The relevant literature was reviewed. Results: Four tumors were located in the tonsils, 2 tumors in the lymphoid nodes and one tumor in the adenoid.The patients were 3 males and 4 females patients with a median age of 24 years (range, 6 to 39 years).Microscopically, entirely follicular pattern was present in one case, entirely diffuse pattern in 2 cases, and follicular and diffuse pattern in other 4 cases. The tumor cells were medium to large in size and showed the morphology of centroblasts or blastoid cells with irregular nuclei, brisk mitotic activity in 3 cases and starry sky in 2 cases. All of the cases were positive for CD20, PAX-5, bcl-6, and MUM1 and had a Ki-67 index>80%, while CD10 and bcl-2 were positive in 3 cases. IRF4 gene rearrangement was identified in all cases and bcl-6 gene rearrangement in 2 cases. All patients presented with localized disease with clinical stage Ⅰ or Ⅱ, except one with stage Ⅳ at presentation and a new lesion in the mediastinum developed 8 months later. Conclusions: LBCL with IRF4 rearrangement is a clinicopathologically distinct entity. The observations reveal a broader spectrum of morphology and biological behaviors. The relationship between clinical stage and prognosis needs to be determined in more cases.

[Bronchiolar adenoma: a clinicopathological analysis of 15 cases].

Objective: To study the clinicopathological characteristics, diagnosis and differential diagnosis of bronchiolar adenoma (BA). Methods: Fifteen cases of BA were collected from the First Affiliated Hospital of Nanjing Medical University, from January 2016 to October 2019. The clinical data, imaging examination, morphology, immunostaining and molecular changes were retrospectively analyzed. Results: There were 3 males, 12 females, most of the patients were female, mainly in middle-aged to elderly (51-77 years). Three had smoking history. The patients usually had no clinical symptoms. Imaging findings were ground-glass and/or lobulated nodules. Grossly, the tumors were gray-whitish, taupe solid or focally microcystic nodules with distinct boundary but no capsule. The maximum diameter was 0.4-2.5 cm (mean 1.0 cm). Histologically, there were glandular, papillary, or flat patterns that were composed of basal cells, mucous cells, ciliated cells and type Ⅱ pneumocytes, some of which showed basal cell proliferation and squamous cell metaplasia. However, there were some cases with few or even without mucous and/or ciliated cells. Immunostaining highlighted the continuous basal cell layer (positive for p63, p40 and cytokeratin 5/6), which was the most important diagnostic evidence. Genetic tests did not show mutation in BRAF or EGFR genes. All patients were followed up for 1-41 months, and they were without recurrence or metastasis. Conclusions: BA is a benign neoplasm that develops in the peripheral lung with good prognosis. Definite diagnosis is very crucial for surgical treatment, especially in frozen consultation. Immunohistochemistry will be helpful if necessary.

[Clinicopathological significance of cyclin D1 expression in Rosai-Dorfman disease].

Objective: To study the clinicopathological significance of cyclin D1 expression in Rosai-Dorfman disease (RDD). Methods: Seventeen cases of RDD were evaluated by HE, immunohistochemical staining and molecular genetic analysis. Expression of cyclin D1 was compared between RDDs and control group that included 29 cases of reactive histiocytosis, 9 cases of IgG4-related disease, and 2 cases of Erdheim-Chester disease. Results: Cyclin D1 was expressed in RDDs (17/17), reactive histiocytosis (11/29), IgG4-related diseases (3/9), and Erdheim-Chester disease (2/2), respectively, with nuclear staining in the RDD cells or proliferative histiocytes. Chi-square test showed that expression of cyclin D1 was significantly higher in RDDs than in reactive histiocytosis and IgG4-related diseases (P<0.01), but not in Erdheim-Chester diseases (P>0.05). The expression threshold for recalculating the percentage of cyclin D1 positive cells was 27.5% (AUC=0.981, P<0.01) by ROC curve. However, CCND1 gene had no rearrangement detected by fluorescence in situ hybridization, but with increased copies of gene in some RDD cells. ARMS-PCR analysis also did not detect KRAS, BRAF and NRAS gene mutations in any cases. Conclusions: Cyclin D1 may serve as an additional diagnostic marker for RDDs. Its high expression may be related to activation of MAPK pathway, but the pathogenetic significance of cyclin D1 in RDDs needs further study.

[Pulmonary artery intimal sarcoma: a clinicopathological analysis of three cases].

Objective: To investigate the clinicopathological characteristics, genetic features, diagnosis and differential diagnosis of pulmonary artery intimal sarcoma (PAIS). Methods: Three cases of PAIS were collected from Jiangsu Province People's Hospital (from February 2016 to November 2019). The clinical data, imaging examination, morphology, immunostaining, and molecular changes were retrospectively analyzed. Results: There were 1 male and 2 females (age: 32, 50, 60 years), who had symptoms of cough, asthma or chest tightness. Imaging findings indicated low density filling defects which were suspected as thrombus, embolism or myxoma. Grossly, the main tumor was located in the elastic arteries and their lobar branches, also extended into the atrium and ventricle, with lung parenchymal infiltration focally. Microscopically, tumor cells were predominantly composed of abundant spindle cells with obvious atypia and myxoid background, resembling fibroblastic or myofibroblastic differentiation. Active mitotic figures and necrosis could be seen in some areas. Immunohistochemical staining of vimentin was strongly positive, while pan-cytokeratin, S-100, desmin, Fli-1, CD31, SMA and ERG etc were variably positive only in focal areas. FISH detection showed amplification of MDM2 gene in three cases and EGFR gene in two cases. Metastatic lesions were found in one case by 18, 32 and 42 months after surgery respectively. There was no recurrence or metastasis in the other two cases. Conclusions: PAIS is one of exceptionally poor differentiated mesenchymal tumor that arises from the arterial intima of elastic pulmonary arteries. There was no definite differention in morphology. Gene detection shows amplification of MDM2 and EGFR gene. This tumor often has poor prognosis with aggressive behavior. Complete resection is the only effective therapeutic option. There is disagreement as to whether chemotherapy and radiotherapy can improve survival.

[Concordance of PD-L1 expression detected by two immunohistochemical platforms and antibodies].

Objective: To evaluate the concordance of PD-L1 expression in various tissues using antibodies 28-8 and SP263 on their respective detection platforms. Methods: Three hundred seventy four specimens of surgical resection of pulmonary diseases in the First Affiliated Hospital of Nanjing Medical University from January 1, 2012 to January 31, 2017 were collected. Totally 374 cases were tested for PD-L1 expression using the two antibodies, 28-8 and SP263, by respective detection platforms (Dako and Ventana). Finally, 336 cases were used for further evaluation, and the results were statistically analyzed for concordance. Results: For non-small cell lung carcinoma (NSCLC), the positive rate of PD-L1 was 57.5% (177/308) using SP263, and 57.5% (177/308) using 28-8 antibody. The correlation coefficient was 0.97 (P<0.01). The positive rate of both benign lung diseases and paracancerous tissues was about 10.7% (3/28), and the positive concordance rate was 100.0%. The distribution of both antibodies was also relatively consistent. Conclusions: The expression levels of 28-8 and SP263 antibodies in NSCLC and other tissues are relatively consistent, suggesting both antibodies may be complementary and substitute for each other, which may be useful in guiding clinical management.

[Clinicopathological observation of adamantinoma of long bone].

Objective: To investigate the clinicopathological features and differential diagnosis of adamantinoma of long bone. Methods: Seven cases of adamantinoma on long bone were selected at Jiangsu Province People's Hospital from June 2012 to May 2018. Clinicopathologic details, immunohistochemical and molecular analysis were performed,and the relevant literature reviewed. Results: There were 6 males and 1 female patients,age ranging from 21 to 60 years (mean 38 years). Six cases were on the right side and one case was on the left; in five cases the tumors arose from tibia, one from patella and one from humerus. Microscopically,tumour cells were mainly composed of spindle cells arranged in bundles or braids,with irregular epithelial island. Immunohistochemically,the epithelial island expressed high molecular weight cytokeratin but not CK8/18. Both epithelial and spindle components expressed vimentin. One case that was microscopically similar to intraosseous synovial sarcoma did not show SYT gene rearrangement. Clinical follow-up was available for five patients: one patient had axillary metastases seven months after operation, one patient had recurrence 34 months after surgery, 3 patients were uneventful with follow up duration from half a month to 32 months. Conclusion: Adamantinoma occurring in long bones is very rare. The correct diagnosis requires adequate sample selection, careful morphologic observation, immunohistochemistry and molecular genetics.

[Clinicopathologic features with collecting duct carcinoma of kidney: report of 10 cases].

Objective: To study the pathological features, immunophenotypes, differential diagnoses and prognostic parameters of collecting duct carcinoma of the kidney (CDC). Methods: Clinical imaging, histopathology, immunohistochemistry, and survival data of 10 patients at First Affiliated Hospital of Nanjing Medical University from January 2009 to August 2017 were retrospectively analyzed along with a review of literatures. Results: The clinical symptoms of CDC were not specific, and image examinations showed space-occupying mass lesions. Tumors were mainly located in renal medulla with grey and firm cut face and the presence of focal hemorrhage and necrosis. Microscopically, there were predominant tubular or tubular-papillary structures with associated focal sarcomatoid areas, desmoplastic stromal reaction and lymphoplasmacytic cells infiltration. Tumor cells had marked cytological atypia with high grade nuclei, conspicuous nucleolus and numerous mitoses. Immunohistochemically, tumor cells were strongly positive for CK19, E-cadherin, vimentin, HCK, CK7 and PAX8. The main treatment was radical nephrectomy in the patients. Seven cases died of CDC with median survival of 10 months. Conclusions: CDC is a rare, highly aggressive malignancy of kidney with poor prognosis. Definitive diagnosis should be made by histology and immunohistochemistry. Differential diagnoses include papillary renal cell carcinoma(type Ⅱ), renal medullary carcinoma, infiltrating high grade urothelial carcinoma, renal pelvis adenocarcinoma and metastatic adenocarcinomas.

[Clinicopathologic features of mammary microglandular adenosis with carcinoma: a study of 5 cases].

Objective: To study the clinicopathologic, immunohistochemical features, differential diagnoses and prognosis of mammary microglandular adenosis with carcinoma (MGACA) with micropapillary pattern. Methods: Five cases of MGACA were collected from 2010 to 2016 and reviewed for their clinical, histologic features and outcome.EnVision method were done for S-100 protein, cytokeratin (CK), p63, Calponin, smooth muscle myosin heavy chain (SMMHC), PR, ER and HER2. Results: Histologically, microglandular adenosis(MGA), atypical MGA (AMGA) and invasive carcinoma were seen in all five cases of MGACA. The invasive component was metaplastic carcinoma in one case and ductal in four cases. All epithelial cells were S-100 and CK positive in MGA, AMGA and invasive carcinoma. p63, Calponin and SMMHC negativity confirmed the lack of a myoepithelial cell layer in MGA, AMGA and MGACA. PR was weakly focally positive in one case, but ER and HER2 were negative in all cases (four cases were triple negative). Ki-67 index was 20% to 40%. Laminin and collagen Ⅳ staining showed the presence of basement membrane in MGA and AMGA, except MGACA. The follow-up time ranged from 3 months to 6 years, and all patients were alive without recurrence or distant metastasis. Conclusions: MGACA is a rare tumor with distinct morphological and IHC features. Compared to most triple-negative breast cancers, MGACA seems to have a relatively favorable outcome.

[Correlation analysis of PD-L1 expression and prognosis in triple-negative breast cancers].

Objective: To investigate the relationship between PD-L1 expression and the clinicopathologic features and prognosis in triple-negative breast carcinomas (TNBC). Methods: All 142 cases of TNBC were collected from the First Affiliated Hospital of Nanjing Medical University from February 2011 to December 2014, and the surgical excision or biopsy specimens from patients without chemotherapy and radiotherapy were included. Histopathologic analysis of stromal tumor infiltrating lymphocyte (sTIL) was performed on HE sections, and PD-L1 immunohistochemical staining was done with MaxVision. Results: The PD-L1 expression rate was 34.5% (49/142) in tumor cells, and was 62.0% (88/142) in sTIL. The PD-L1 expression in tumor cells was positively correlated with tumor size (r=0.181, P=0.031), Ki-67 index (r=0.211, P=0.012), sTIL (r=0.380, P<0.01) and PD-L1 expression in sTIL (r=0.447, P<0.01). The PD-L1 expression in sTIL was positively correlated with tumor grade (r=0.215, P=0.01), Ki-67 index (r=0.253, P=0.002) and sTIL (r=0.370, P<0.01). The high stromal CD8(+) /FOXP3(+) ratio was significantly associated with improved overall survival (χ(2)=4.186, P=0.041). The high percentage of sTIL was significantly associated with improved overall survival (χ(2)=12.427, P<0.01) and progression-free survival (χ(2)=4.057, P=0.044). Conclusions: In TNBC, PD-L1 expression is positively correlated with Ki-67 and sTIL; the stromal CD8(+) /FOXP3(+) ratio and sTIL are significantly associated with prognosis. The PD-L1 expression, stromal CD8(+) /FOXP3(+) ratio and sTIL are biologically important in TNBC, and all these correlative factors are important potential parameters in assessing immunotherapy for TNBC.