Search

Objective: To investigate the correlation between the expression of CD117, MITF, NAT10 and clinical parameters in sinonasal mucosal melanoma (SNMM). Methods: Formalin-fixed paraffin-embedded tumor specimens of 80 cases of SNMM at the Eye, Ear, Nose and Throat Hospital, Fudan University, from December 1999 to November 2013 were analyzed for CD117, MITF and NAT10 expression by immunohistochemistry. Results: There were 40 men and 40 women. The median age was 61 years, age 26 to 85 years. There was no correlation of the expression of CD117, MITF and NAT10 with the patients' age, gender, tumor site, stage, therapy method and brain metastases ( P >0.05). The expression of MITF and NAT10 was associated with lymph node metastasis and the tumors were more likely to metastasize when MITF and NAT10 were positive. However, expression of CD117 had no correlation with lymph node metastasis. Log-rank test revealed that the expression of CD117 was correlated with both three-year and five survival rate ( P =0.012, P =0.023; respectively) and patients with tumor having low expression of CD117 had the worse outcome. COX test revealed that low CD117 expression, advanced age and lymph node metastasis were independent risk factors ( P <0.05). No significant association was found between the expression of CD117, MITF and NAT10 with disease free survival ( P >0.05). Conclusions: Patients with SNMM expressing low level of CD117 have decreased survival rate. Tumors with high level of MITF and NAT10 expression are more likely to metastasize. The expression level of CD117 can be used as an important indicator for the patient survival, and the expression of MITF and NAT10 can be used as a predictor of tumor metastasis.

Objective: To investigate the clinicopathologic and differential diagnostic features of glomus tumor of the kidney. Methods: Four cases of glomus tumor of the kidney were collected from the archives of Peking University Third Hospital, the Second Hospital of Tianjin Medical University, Ningbo Yinzhou Second Hospital and Zhejiang Provincial People's Hospital between January 2012 to June 2017; the clinical and radiologic features, histomorphology, immunohistochemistry, ultrastucture and prognosis were analyzed and the relevant literature was reviewed. Results: Patients consisted of 2 men and 2 women with ages ranging from 37 years to 66 years (mean 55 years). Three patients had history of hypertensive disease (grade Ⅱ, 3 to 10 years). The tumors measured in maximum diameter from 3.0 cm to 4.0 cm (mean 3.6 cm) and showed gray-white to yellow and tan on cut surface. Macroscopical examinations showed all tumors were circumscribed but non-encapsulated. Histologically, 1 tumor presented as glomus tumor with extensive myxoid change, 1 as cellular and solid pattern glomus tumor, 1 as glomangioma with focal myopericytoma-like pattern and 1 as symplastic glomus tumor with areas resembling myopericytoma. The tumor cells in two cases showed scant cytoplasm and uniform, bland-appearing nuclei without mitoses. In one case, the tumor cells were epithelioid with abundant eosinophilic cytoplasm and relatively well-defined cell borders. There was an increased mitosis of 4/50 HPF; however, no evidence of atypical mitosis or nuclear atypia was noted. In the symplastic glomus tumor the tumor cells showed frequently nuclear pleomorphism without mitoses. By immunohistochemistry, all tumors showed strong and diffuse reactivities to at least 3 of the 4 muscle-associated markers (SMA, h-Caldesmon, MSA and Calponin), 3 tumors strongly and diffusely expressed collagen Ⅳ, 2 expressed CD34 and 1 focally expressed desmin; whereas markers including epithelial, neuroendocrine, nephrogenic, melanoma-associated, STAT6, S-100 protein, CD117 and β-catenin all were negative in all the 4 tumors. Ultrastuctural analysis was done in 2 cases and showed prominent cytoplasmic actin bundles and pericellular basement membrane, and lacking of rhomboid renin crystals in both tumors. The hypertension persisted after surgical resection for all the 3 patients with this medical history. Follow-up information (range: 6-64 months, mean: 44 months)showed that no evidence of local recurrence or distant metastasis was identified in all 4 patients. Conclusions: Glomus tumor rarely occurs in the kidney and usually has a good prognosis. Careful attention to its morphology with the judicious use of immunohistochemistry and ultrastuctural analysis can be helpful for its diagnosis and differential diagnosis.

Objective: To investigate the clinicopathologic features, immunophenotype, pathological diagnosis and treatment of malignant mixed tumor (MMT). Methods: Clinical and pathological features including immunohistochemical phenotypes were analyzed in a case of MMT accompanied with eccrine porocarcinoma (EP) involving both hands, diagnosed definitely in January 2018 along with review of relevant literature. Results: A 64-year-old man presented with multiple rash on both hands for 4 years. Three lesions of 0.5 to 2.2 cm were removed for pathological evaluation. The pathological changes on little finger of left and right hands were MMT with EP, whereas that removed from the right ring finger was EP. MMT showed infiltrative growth with vascular wall invasion and consisted of epithelial (glandular or tube differentiation) and mesenchymal components (mucinous and/or cartilage stroma). The endothelial cells showed moderate to severe cytological atypia, nuclear pleomorphism and increased mitotic activity. The glandular component had histological characteristics of syringocarcinoma with moderately atypical chondrocytes but without myoepithelium. EP was composed of basal cells with visible vacuoles in cytoplasm and the presence of tubular and squamous differentiation, along with obvious atypia. Immunohistochemically cavosurface epithelium of glandular differentiation of MMT showed positivity for CK7, EMA and CD117. Myoepithelium showed S-100, CK5/6 and p63 positivity and stromal cells were positive for S-100. Differential diagnoses included metaplastic carcinoma, malignant myoepithelioma and atypical mixed tumor of skin. Conclusions: MMT with EP is extremely rare.The diagnosis of MMT depends on the morphologic features. Immunohistochemical staining is helpful for differential diagnosis. Surgical excision with safety margins is the treatment of choice. Complementary radiotherapy and/or chemotherapy is still controversial. The clinical course of MMT is deemed unpredictable and long-term follow-up is necessary.

Objective: To study clinical and pathologic characteristics of leiomyomas of the gastrointestinal tract, and to investigate the distribution characteristics of interstitial cells of Cajal ( ICCs ) in gastrointestinal leiomyomas. Methods: One hundred and forty-seven cases of leiomyomas of gastrointestinal tract were collected at the Second Affiliated Hospital of Zhengzhou University from June 2012 to June 2017. Clinical and pathologic findings were analyzed, combined with immunohistochemistry, Alcian blue-osafranin staining and molecular study. Results: The age of patients ranged from 13-82 years with mean age of 52 years. Male to female ratio was about 1∶2. Histologically, all tumors were composed of ovoid to spindle cells arranged in short intersecting fascicles. All tumors were diffusely and strongly positive for smooth muscle antibodies, desmin and h-caldesmon by immunohistochemical staining. A prominent interspersed subpopulation of elongated/dendritic-like cells with CD117 and DOG1 positivity (accounting for 1% to 30% of all tumor cells) and negative for Alcian blue-osafranin staining was identified in all esophageal leiomyomas, 16 of 20 (80%) gastric leiomyomas and 3 of 12 small bowel leiomyomas, but none in colonic/rectal leiomyomas. Mutational analysis in 16 cases showed absence of mutation in exons 9, 11, 13 or 17 of C-KIT and exons 12 or 18 of PDGFRA. Conclusions: ICCs are identified in esophageal and gastric leiomyomas, as well as in small percentage of intestinal leiomyomas. Such findings may bring significant diagnostic pitfalls for misdiagnosis as gastrointestinal stromal tumor. Careful attention to the distribution of CD117 and DOG1 positive cells and molecular mutation analysis of C-KIT and PDGFRA may be necessary to establish the correct diagnosis.

Objective: To investigate the clinicopathological features of mammary analogue secretory carcinoma (MASC) of salivary glands, and its diagnosis, differential diagnosis, immunohistochemistry and molecular pathology. Methods: Seventeen cases of MASC were enrolled, with 9 cases of salivary acinar cell carcinoma and 18 cases of adenoid cystic carcinoma as control groups from Nanjing General Hospital from 1997 to 2014 were included in this retrospective study, combined with immunohistochemistry and molecular detection of ETV6-NTRK3 gene fusion. All cases were histologically reviewed with immunohistochemical staining (EnVision) for S-100 protein, SOX10, GATA3, CD117 expression in each group. Fluorescence in situ hybridization (FISH) was used to detect the ETV6-NTRK3 gene fusion. Results: The age of MASC patients ranged from 27 to 74 years with mean age of 47 and ratio of male and female was 4∶3. All cases showed infiltrative growth and diverse cytology and histology, including lobular (8 cases), cystic papillary (3 cases), cribriform mixed with papillary and glandular structures (6 cases) at various proportions. Some tumors of MASC also exhibited solid growth areas with occasional microcystic honeycombed pattern composed of small cysts merged into larger cysts resembling thyroid follicles. S-100 protein and SOX10 were strongly positive in all MASC cases (17/17). In addition, there was insignificant positivity for GATA3 (3/17) and CD117 (4/17). ETV6 gene fusion detection was informative in 12 MASC cases by FISH with 10 positive cases and 2 negative cases. Conclusions: Combined immunohistochemical positivity of S-100 protein, CD117 and SOX10 are useful in the diagnosis and differential diagnosis of MASC. FISH detection of ETV6-NTRK3 fusion offers an additional molecular diagnostic marker for the diagnosis.

Objective: To investigate the morphological features and immunophenotypes of eosinophilic renal tumors in order to provide references for the differential diagnosis of this tumor. Methods: A cohort of 75 cases of eosinophilic renal tumors were collected. The morphological features of the tumors were observed under microscope, and the immunophenotypes of the tumors were detected using tissue microarray and immunoshistochemistry. Results: There were some overlaps between the different types of eosinophilic renal tumors in morphology, but each had its distinct characteristics. Immunohistochemically, renal oncocytoma (RO) and eosinophilic chromophobe renal cell carcinoma (ChRCC) shared some common immumophenotypes, except for the expression of CK7, with the expression rates of 2/19 in RO and 17/20 in eosinophilic ChRCC, respectively. Eosinophilic clear cell renal cell carcinoma mainly showed positive immunostaining for Vimentin and CAⅨ, whereas negative for CK7 and CD117 in most cases (10/15). AMACR was diffusely expressed in the majority of eosinophilic papillary renal cell carcinoma (PRCC, 10/13). Furthermore, vimentin, CK7 and CD10 were positively expressed in eosinophilic PRCC with the expression rates of 8/13, 9/13 and 6/13, respectively; while CAⅨ, CD117 and TFE3 were all negatively expressed in eosinophilic PRCC.Epithelioid angiomyolipoma generally showed positive expression of vimentin, SMA and HMB45, but negative expression of CAⅨ and CK7. Vimentin, CD10, AMACR and TFE3 were strongly expressed in XP11.2 translocation renal cell carcinoma; on the contrary, CK7, CD117 and HMB45 were not expressed in the majority of the tumor. Conclusion: With full understanding of the morphology of different types of eosinophilic renal tumors, the immunostaining of vimentin, CAⅨ, CK7, CD10, AMACR, CD117, TFE3 and HMB45 could play a crucial role in the differential diagnosis of these tumors.

Objective: To explore the ultrastructural features and mutation status of platelet-derived growth factor receptors A (PDGFRA) and c-kit in gastrointestinal stromal tumors that were immunohistochemically negative for CD117 antigen., Methods: Six cases of gastrointestinal stromal tumors that were CD117 immunostain negative were studied by electron microscopy. Direct PCR sequencing was used to investigate the mutation status of c-kit gene exons 9, 11, 13, 17 and PDGFRA gene exons 12 and 18., Results: The ultrastructural features of all 6 cases were similar to those of the interstitial cell of Cajal (ICC). None of the 6 cases were found to have c-kit gene mutations. However, three tumors were found to harbor PDGFRA exon 18 activating mutations, including two tumors having an Asp-->Val842 missense mutation and one having an Arg-->Ser841 missense mutation., Conclusions: PDGFRA mutations may provide an important alternative molecular mechanism for the development of gastrointestinal stromal tumor.

Objective: To explore the clinicopathological and immunohistochemical features of extra-gastrointestinal stromal tumors (EGIST) arising from the omentum and mesentery and to investigate the cellular origin of these tumors, prognostic factors, and the relationships with gastrointestinal stromal tumors., Methods: Nineteen cases of mesenchymal neoplasms arising from the omentum and mesentery (previously diagnosed as smooth-muscle tumors or schwannomas) were studied morphological with a panel of immunohistochemistry including CD117 and CD34., Results: Among the 19 cases, 14 tumors were confirmed to be EGIST, of which 6 tumors arose from the omentum and 8 cases located at the mesentery. The size of tumors ranged from 3.5cm to 29.0 cm (mean 12.4cm) in diameter. Histologically, there were 9 cases of mainly spindle cell type, 2 cases of mainly epithelioid cell type and 3 cases of mixed cell type. all EGIST expressed CD117 (14/14) and a percentage of them expressed also CD34 (8/14) and/or SMA (6/14), anyhow, all EGIST were negative for desmin and S-100 protein. Six patients with tumors arising from the omentum were all alive without evidence of disease (tumor-free). Among 7 cases with tumors of the mesentery, three patients died of the disease, 1 alive with the disease and 3 patients alive without evidence of the disease., Conclusions: EGIST were identical by their histological and immunohistochemical features with gastrointestinal stromal tumors (GIST). This tumor may arise from the multipotential mesenchymal stem cells. EGIST have various clinical behavior, and the parameters used for predicting the prognosis of GIST may not be completely suitable for EGIST evaluation.

Objective: To study the clinicopathological characteristics, immunohistochemical features and differential diagnosis of hepatic angiomyolipoma (AML)., Methods: The clinicopathological features of hepatic AML were systematically examined in 44 surgically resected tumor specimens, with additional immunohistochemistry study using 10 relevant antibodies., Results: The tumors were composed of various amounts of three components, i.e. blood vessels, smooth muscle cells and adipose cells. According to the proportions of each of these tissue components, AML was subcategorized into the classical type (n = 13), myomatous type (n = 25), lipomatous type (n = 4), and angiomatous type (n = 2). Myoid cells displayed various morphology, including epithelioid, intermediate (ovoid or short spindle), spindle, oncocytic, and pleomorphic features. Hematopoietic elements were present as minor findings in eight tumors. Immunohistochemically, the tumor cells were strongly positive for HMB45 (44/44, 100%), SMA (38/38, 100%) and CD117 (30/38, 78.9%)., Conclusions: A correct diagnosis of hepatic AML might be difficult due to its various growth patterns and cell types. HMB-45 positivity in the myoid cells is a key feature for hepatic AML. CD117 may be another useful ancillary marker for reaching a definite diagnosis.

Objective: To study the histogenesis and pathological characteristics of gastrointestinal stromal tumors (GIST) and GIST type stromal tumor (ST) beyond the gastrointestinal tract., Methods: A retrospective study was carried out on leiomyoma, leiomyosarcoma and neurilemoma (46 cases in gastrointestinal tract and l3 cases in urinary tract and perineal area). 4 antibodies (CD117, CD34, SMA, S-100) were used for immunohistochemical staining., Results: Among 45 cases of GIST, the positive rate of CD117 and CD34 was 93.3% and 88.9% respectively. Among 12 cases of GIST type ST beyond the gastrointestinal tract, the positive rate of CD117 and CD34 was 83.3% and 75.0% respectively. In 2 cases (1 in gastrointestinal tract) of leiomyomas, both CD117 and CD 34 were negative in tumor cells, while SMA was extensively positive., Conclusions: CD117 and CD34 positivity are the most valuable factors in diagnosing ST. Both GIST and GIST type ST beyond the gastrointestinal tract are considered originating from a proto-interstitial stem cell with disoriented differentiation.

Objective: To explore the origin and differentiation of gastrointestinal stromal tumors (GISTs)., Methods: Immunohistochemistry staining and electron microscopy were adopted., Results: In 212 cases of primary GISTs, the positive rates of CD117, CD34, alpha-SMA, MSA, desmin, S-100, PGP9.5 were 96.7%, 77.3%, 19.3%, 15.6%, 1.9%, 16.3%, and 12.3% respectively. Among them, GISTs showed a diffuse and strong positivity for CD117. Electron microscopy of tumor cells demonstrated numerous mitochondria, prominent perinuclear Golgi complex, smooth and rough endoplasmical reticulum and intermediate filaments. Irregular caveolae, dense plaque, incontinuous basal lamina were observed occasionally. Cytoplasmic processes were often observed accompanying with local adhesion present between the processes or between the processes and the cell membrane., Conclusions: Data from both immunophenotype and electron microscopy suggest that GIST might originate from the mesenchymal cells, differentiating to be ICC afterwards, and possessing myoid characteristics in various extent.

Objective: To explore the clinicopathological, immunohistochemical, and molecular biologic characteristics of esophageal stromal tumors and smooth muscle tumors., Methods: Twenty four cases of esophageal mesenchymal tumors were reclassified by a panel of antibodies such as CD117, CD34 etc. The sequence of 11 exon of c-kit gene were detected in some cases., Results: There were 3 cases of esophageal stromal tumors, 20 leiomyomas, and 1 leiomyosarcoma. The 3 esophageal stromal tumors occurred in 3 men aged 71, 56 and 60 years respectively. The tumors originated from muscularis propria with the size of 4 cm, 8 cm and 14 cm in diameter. Microscopically, the tumor cells were spindle and epithelioid shaped with slightly basophilic appearance, arranged in intersecting fascicles, diffusing and palisading patterns. Immunohistochemically, the tumors were positive for CD117 and CD34. The mutation of 11 exon of c-kit gene was detected in one case. In comparison, esophageal leiomyomas occurred in a younger population. The age ranged from 30 to 60 years (mean age 41.6 years), 12 male cases, 8 female cases. 15 cases of esophageal leiomyomas were intramural tumors with a diameter of 0.8 - 10.5 cm (mean 4.5 cm) originating from muscularis propria and 5 cases which were intraluminal polyps with a diameter of 0.2 - 1.0 cm originating from muscularis mucosae. Leiomyomas were strongly eosinophilic in appearance, diffuse positivity for alpha-SMA, MSA, and desmin, and no c-kit gene mutation. One male case of leiomyosarcoma had a diameter of 5 cm and originated from muscularis mucosae and displayed a sausage-shaped polyp., Conclusions: Leiomyoma is still the most common mesenchymal tumor of the esophagus, the stromal tumor can be similar to gastrointestinal stromal tumors. Typical esophageal leiomyosarcoma is very rare and has different clinicopathologic and molecular biologic features.