Nodular Histiocytic/Mesothelial Hyperplasia In The Greater Omentum Of Patients With Ovarian Cancer

【Background】Nodular histiocytic/mesothelial hyperplasia (NHMH) is designated as a benign proliferative process predominantly composed of histiocytes with scattered mesothelial cells. It has been identified from hernia sacs, transbronchial biopsies, pulmonary specimens from patients with pneumothorax, and pelvic surgery speciemens. Similar lesions have also been reported in cardiac surgical procedures. NHMH is sometimes misdiagnosed as malignancies or metastatic tumors in cancer patients. In this study, we further retrospectively investigated the greater omental specimens from 96 patients with gastrointestinal malignancies and 53 patients with gynecologic neoplasms, and found visible NHMH with prominent T lymphocyte infiltration in 3 out of the 53 patients with gynecologic neoplasm.【Objectives】1. To analyze clinical and pathological features about NHMH in the greater omentum of patients with ovarian malignancies; 2. To investigate pathogenesis of nodular histiocytic/mesothelial hyperplasia (NHMH) and the mechanisms of the aggregation of histiocytes in the NHMH lesions.【Methods】1. 3 cases of visible greater omental nodular histiocytic/mesothelial hyperplasia (NHMH) were studied by routine H&E staining and immunohistochemistry methods.2. 149 greater omental specimens from patients with gastrointestinal and ovarian malignancies were studied retrospectively to looking for the NHMH lesions;【Results】1. In the 149 cases, There were 96 cases (54 males and 42 females, aged 31-82 years with an average age of 51 years) with gastrointestinal malignancies who underwent total or partial omentectomy (including 62 cases gastric adenocarcinoma, 8 cases gastrointestinal stromal tumor, and 26 cases colonic adenocarcinoma), There were 53 cases (females aged 6-73 years with an average age of 51 years) with primary ovarian tumors who underwent total or partial omentectomy (including 12 cases high grade serous adenocarcinoma, 11 cases low grade papillary serous cystadenocarcinoma, 6 cases borderline mucinous cystadenoma, 11 cases borderline serous cystadenoma, 7 cases granulosa-cell tumor, 3 cases juvenile granulosa-cell tumor, 2 cases endodermal sinus tumor, and 1 case of malignant Sertoli-Leydig cell tumor).2. The morphology and immunophenotype of the special cases were presented as follows:1) Gross appearance of the greater omentums: Small yellow-red nodules on the greater omentum were present in 3 cases. The small nodules varied in size from 0.2-0.6 cm in diameter. Clear ascites was noted upon opening the abdominal cavity in case 1 and 2, and sanguineous ascites was found in case 3;2) Microscopic Features: The greater omentum with NHMH lesion showed an inflammatory background, it was infiltrated with a large amount of lymphocytes, focal plasma cells, and few lymphoid follicles were found. The NHMH lesions were composed of sheets of cohesive polygonal to oval epithelioid cells with distinct cell borders, abundant eosinophilic cytoplasm and inconspicuous nucleoli. In case 1 and 2, NHMH lesions were also found on the surface of appendix and fallopian tube. The NHMH-like lesion was also found in the cell block from the peritoneal washings of case 2, the mononuclear cells also showed bland morphology with oval nucleolus and abundant eosinophilic cytoplasm;3) Immunohistochemistry: The mononuclear cells on the surface of the greater omentums showed diffuse and strong reactivity against CD68 and CD163, markers for histiocytes, in all 3 cases of NHMH. These cells stained positive for vimentin, but negative for AE1/AE3, CK5/6, calretinin, mesothelin and WT-1, and also negative for the epithelial marker Ber-EP4 and MOC-31. MIB-1 staining indicated that the cells had very low proliferative activity (<1%). There were few scattered mesothelial cells among the mononuclear cells that stained positive for calretinin, CK5/6, mesothelin, WT-1 and AE1/AE3. The scattered lymphocytes infiltrated in the lesion were demonstrated to be predominantly T helper cells by positive immunostain of antibodies against CD3,CD4,CD8,CD20 in all 3 cases. The cells in the cell block from the ascite of case 2 also showed positive for CD68 and CD163, negative for calretinin, CK5/6 and mesothelin. Scattered calretinin positive mesothelial cells were seen among the mononuclear cells;【Conclusions】1. This report has first demonstrated visible NHMH in the greater omentum of patients with ovarian malignancies, and awareness of this entity should be brought to clinicians to avoid misdiagnosis.2. Nodular histiocytic/mesothelial hyperplasia (NHMH) is designated as a benign proliferative process predominantly composed of histiocytes with scattered mesothelial cells.3. In this study, we suggest that there is likely a chronic inflammatory component in the process of NHMH and the interaction between CD4+ helper T cells and macrophages may play an important role in the aggregation of histiocytes in the NHMH lesions.