Huaiyin Shi

Primary gastric inflammatory myofibroblastic tumor: A clinicopathologic and immunohistochemical study of 5 cases

Primary gastric inflammatory myofibroblastic tumors are rare. Here we report on 5 such cases (4 males and 1 female, age range 36-45 years). Their presenting symptoms included abdominal mass (5 patients), abdominal pain (4 patients), and upper gastrointestinal hemorrhage (1 patient). Tumor size ranged from 4.5 to 8 cm in the greatest dimension. Histologically, these tumors showed three patterns: myxoid hypocellular, fascicular, and hyalinized. A lymphoplasmacytic infiltrate was present in all 5 tumors. One to two mitotic figures were recognized in 10 high power fields (HPFs) in 4 patients and focally up to 5 in 10HPFs in 1 patient. No prominent nuclear atypia or necrosis was observed. ALK, smooth muscle actin, and vimentin staining were observed in all tumors. One tumor focally expressed desmin. S-100, CD21, CD34, CD35, CD68, and CD117 were negative in all IMTs. The patients were followed up for 2-5 years (mean 3.4 years), and none of them had tumor metastasis or died. Only one patient developed local recurrence and is now alive with no evidence of disease after the second surgery (11 months after the second surgery). Our results indicate that primary gastric IMTs have an intermediate behavior as seen at other sites.

Clinicopathologic analysis of 4 perivascular epithelioid cell tumors (PEComas) of the gastrointestinal tract.

This study describes the clinical, histologic, and immunohistochemical features of four cases of GI PEComa. The size of the tumors ranged from 3.5 to 6.0cm in diameter, and all were located in wall of the large bowel. Microscopically, the tumors were characterized by an epithelioid arrangement of tumor cells, which had abundant clear to pale eosinophilic granular cytoplasm, vesicular nuclei and prominent nucleoli. The stroma was rich in capillaries, a sinusoidal vasculature and thick-walled blood vessels. Mitotic figures were generally rare. Immunohistochemically, the tumors were positive for Vimentin (4/4), HMB-45 (4/4), Melan-A(4/4),alpha-smooth muscle actin (4/4), and desmin (3/4). The patients have been well with no evidence of disease at 8, 15, 32 and 36 months,respectively, after the surgical operation. GI tract PEComas should be regarded as tumors of an uncertain malignant potential until long-term outcome data for a larger number of patients become available.

Inflammatory angiomyolipomas of the liver: a clinicopathologic and immunohistochemical analysis of 5 cases

Hepatic angiomyolipoma (AML) may demonstrate a marked histologic diversity. We report 5 cases of hepatic AML exhibiting prominent inflammatory cells in the background (inflammatory AML). The patients were 4 females and 1 male, with age ranged from 21 to 48 years (mean, 39.2 years). Three tumors were in the left lobe and 2 in the right lobe. The tumor size was from 5.5 to 10 cm in the greatest dimension (mean, 7.46 cm). No patient had clinical features of tuberous sclerosis. Histologically, the striking feature was the infiltration of numerous inflammatory cells in the background of the tumors, including small lymphocytes, plasma cells, and histiocytes. The percentage of tumor area with heavy inflammatory infiltration was more than 50% in all cases. The myoid cells were spindled and epithelioid in shape, with eosinophilic or clear cytoplasm, and were arranged in fascicles and clusters. Scattered adipose cells and sinusoidal and thick-walled blood vessels were variably present in all tumors. Focal trabecular arrangement was present in 2 of the 5 tumors. There was no nuclear atypia, and mitotic figures were rare. The myoid cells were diffusely positive for vimentin, smooth muscle actin, and HMB-45 in all cases. All patients showed no evidence of disease after the initial surgical excision during a follow-up period from 3 to 9 years. The inflammatory AMLs should be distinguished from other tumors with inflammatory background such as inflammatory myofibroblastic tumor and follicular dendritic cell tumor.

LMP1 promotes nasal NK/T-cell lymphoma cell function by eIF4E via NF-κB pathway

Nasal natural killer T-cell lymphoma (NKTL) is a highly malignant tumor that is closely associated with Epstein-Barr virus (EBV) infection. Latent membrane protein 1 (LMP1) is encoded by EBV and plays an important role in EBV-induced cell transformation. Therefore, we assessed the function of LMP1 as a stimulant of NKTL progression and the underlying mechanism. A human EBV-positive NKTL cell line (SNK-6) was transfected with pcDNA3.1-LMP1, LV-LMP1 shRNA or LV-eukaryotic translation initiation factor 4E (eIF4E)-shRNA. Then, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to assess the proliferation of SNK-6 cells, and cell migration and invasion were analyzed by transwell chamber assay. Flow cytometry was used to analyze the cell cycle and apoptosis. The results showed LMP1 was highly expressed in SNK-6 cells compared with control groups. Following pretreatment with LMP1 shRNA, the proliferation of SNK-6 cells was inhibited and resulted in a G0/G1 phase arrest. A reduction in invasion and migration was also observed. LMP1 silencing promoted cell apoptosis. Further mechanistic analysis suggested that LMP1 overexpression induced the expression of eIF4E, while eIF4E-shRNA dramatically attenuated the increase in cell proliferation, invasion, migration and the inhibition of apoptosis triggered by LMP-1 upregulation. Moreover, the effect of LMP1 on eIF4E expression was mediated by the NF-κB pathway. Therefore, this finding may provide a potential target against NKTL.

Clinicopathological features of atypical lipomatous tumors of the laryngopharynx.

Atypical lipomatous tumor (ALT) of the laryngopharynx is rare. Here we report five cases to demonstrate their clinicopathological features. The patients were four males and one female, aged 41 to 69 years (median 53.6 years). All tumors (two in the hypopharynx and three in the larynx) presented as a slowly growing, painless mass. Symptoms included dysphagia (2/5), dysphonia (3/5), and the feeling of a foreign body in the throat (5/5). Tumors were well circumscribed or focally infiltrative, ranging from 2.0 to 5.0 cm (median, 3.4 cm) in size, and microscopically showed the typical features of lipoma-like ALT. Immunohistochemically, tumor cells were stained with S-100, vimentin, murine double minute 2 (MDM-2), and cyclin-dependent kinase 4 (CDK4). Two patients had local tumor recurrences at 6 and 14 months after initial surgery during follow-up. ALT of laryngopharynx is an indolent tumor. Immunohistochemical staining for MDM-2 and CDK4 is helpful in pathological diagnosis.

Primary colorectal inflammatory myofibroblastic tumour: a clinicopathological and immunohistochemical study of seven cases

Aims: Primary colorectal inflammatory myofibroblastic tumours are rare. Here we report seven such cases to demonstrate their clinicopathological features and prognosis. Methods: Clinical and pathological data of seven cases of colorectal inflammatory myofibroblastic tumour were reviewed. Immunohistochemical staining was also performed. Results: The presenting symptoms included abdominal or pelvic mass (7 patients), abdominal pain (7 patients), and lower gastrointestinal haemorrhage (2 patients). The tumour size ranged from 3.8 cm to 6.3 cm in greatest dimension. Histologically these tumours showed three patterns: myxoid hypocellular, fascicular, and hyalinised pattern. A lymphoplasmacytic infiltrate was present in all seven tumours. Mitotic figures were 0∼2 per 10 high power fields (HPF) in five cases and were focally up to 4∼6 per 10 HPF in two tumours. Nuclear atypia was mild in five and moderate focally in two tumours. Necrosis was absent. Anaplastic lymphoma kinase (ALK), smooth muscle actin, and vimentin staining were present in all tumours. S100, CD21, CD34, CD35, desmin, CK, CD68, and CD117 were negative in all inflammatory myofibroblastic tumours. The patients were followed up for 3–8 years (mean 4.9 years). Five patients were alive without evidence of disease after tumour resection. Two patients had a tumour recurrence 14 and 18 months after the initial surgery, respectively. A second surgical resection was performed for the recurrent tumours and the patients have been free of disease since (now 22 and 35 months after the second surgery, respectively). Conclusions: Colorectal inflammatory myofibroblastic tumours are rare, benign or low malignant tumours and ALK positivity is helpful in pathological diagnosis.

Expression of RNA-binding protein LIN28 in classic gastric hepatoid carcinomas, gastric fetal type gastrointestinal adenocarcinomas, and hepatocellular carcinomas: An immunohistochemical study with comparison to SALL4, alpha-fetoprotein, glypican-3, and Hep Par1

INTRODUCTION Gastric hepatoid carcinomas (GHCs) include type I (classic) and type II (fetal type gastrointestinal adenocarcinoma). The classic type shows overlapping morphologic features with those of hepatocellular carcinoma (HCC). The aim of this study is to investigate expression of LIN28 in GHCs and explore its utility to distinguish classic GHC from HCC. METHODS We investigated immunohistochemical expression of LIN28 in 93 primary GHCs (47 type I, 46 type II) and 60 HCCs with comparison to SALL4, AFP, glypican-3, Hep Par1, p-CEA and CK7. We also stained LIN28 and SALL4 in 52 conventional gastric adenocarcinomas to assess their specificity in gastric carcinomas. RESULTS Classic GHCs and fetal type gastrointestinal adenocarcinomas showed positive LIN28 in 21/47 (45%) and 10/46 (22%), SALL4 in 41/47 (87%) and 36/46 (78%), AFP in 30/46 (65%) and 33/46 (72%), glypican-3 in 31/41 (76%) and 24/38 (63%), Hep Par1 in 27/41 (66%) and 28/37 (76%), and CK7 in 15/40 (38%) and 25/38 (66%), respectively. p-CEA staining was seen in 19/44 (43%) classic GHCs. Among HCCs, LIN28, SALL4, AFP, glypican-3, Hep Par1, p-CEA and CK7 was seen in 1/60 (2%), 0/60 (0%), 6/30 (20%), 23/30 (77%), 29/30 (97%), 28/30 (93%) and 21/30 (70%) cases, respectively. LIN28 and SALL4 staining was seen in 2/52 (4%) and 14/52 (27%) gastric conventional adenocarcinomas, respectively. The sensitivity and specificity of distinguishing classic GHCs from HCCs was 45% and 98% for LIN28, 87% and 100% for SALL4, 65% and 80% for AFP, 76% and 30% for glypican-3, 66% and 3% for Hep Par1, 43% and 7% for p-CEA, and 38% and 30% for CK7, respectively. Combining LIN28 and SALL4 increased the sensitivity to 96% with 98% specificity to distinguish classic GHCs from HCCs. CONCLUSIONS LIN28 is a very specific marker (98% specificity) for distinguishing classic GHCs from HCCs though it is not as sensitive as SALL4. AFP, glypican-3, Hep Par1 and p-CEA are not useful in distinguishing classic GHCs from HCCs. Combining LIN28 and SALL4 increased the sensitivity to distinguish classic PHCs from HCCs.