Omentum 

Histologic sections of the omental and peritoneal plaques demonstrate discrete nodules of mature glial tissue with glial cells in a fibrillary background embedded in peritoneal fibrous stroma and omental fat. These nodules are strongly positive for GFAP and S100. Hypercellularity, nuclear atypia, vascular proliferation, necrosis, and elevated mitotic rate are not appreciated. No immature neuroepithelial component is identified in the biopsied plaques. No other germ cell elements are identified. These findings are consistent with a diagnosis of gliomatosis peritonei.  

Gliomatosis peritonei is a rare finding associated with immature and mature teratomas, mixed germ cell tumors, and ventriculoperitoneal shunts. It is more common in younger patients and can be found on any peritoneal surface, including the omentum. When mature glial tissue involves lymph nodes, it is termed nodal gliomatosis. In gliomatosis peritonei, nodules are typically only a few millimeters in size and do not cause symptoms, although they can occasionally cause compressive symptoms due to formation of a large mass (so-called growing teratoma syndrome). They may be associated with ascites.  

Histologically, gliomatosis peritonei is characterized by nodular deposits of mature glial elements. They do not contain any immature neuroepithelial features such as pseudo-rosettes, tubules, or mitotically active nodules of atypical, hyperchromatic glial cells. They also do not contain any non-glial teratomatous elements. It is often found in a background of hemorrhagic, inflamed peritoneum and can be associated with endometriosis. Occasionally, choroid plexus can be present. Gliomatosis peritonei can be diagnosed on H&E, although immunohistochemistry may be performed to confirm glial lineage. Nuclei in mature glial tissue deposits stain strongly with SOX2. The cytoplasm often stains strongly positive with GFAP. Tumor cells can be variably positive for S100 but are negative for OCT4 and NANOG.  

Gliomatosis does not portend an adverse impact on survival in patients with immature teratoma. Gliomatosis alone is considered a World Health Organization (WHO) grade 0 lesion that does not require chemotherapy, even if associated with an ovarian immature teratoma. If complete resection is not possible, many of these patients can be managed with long-term surveillance due to the indolent nature of the lesions. By contrast, if immature neuroepithelial tissue is found in any of the peritoneal nodules, it is treated as a deposit of metastatic immature teratoma. Implants of immature teratoma require treatment with adjuvant chemotherapy, so it is important to ensure that the peritoneal nodules are thoroughly sampled and examined microscopically for immature and non-glial elements. Grading of immature teratoma is based on the number of low-power microscopic fields with immature neuroepithelial elements, which often form rosettes. Rarely, gliomatosis can undergo malignant transformation to malignant glioma. Biopsies should therefore be carefully examined for atypia, necrosis, vascular proliferation, hypercellularity, and mitotic figures.  

Several theories exist regarding the etiology of gliomatosis peritonei. It was initially believed that these lesions resulted from implantation metastases of the original tumor, possibly due to capsular rupture or angiolymphatic dissemination. Recent studies have demonstrated that gliomatosis lesions are genetically unrelated to primary ovarian tumors, supporting an origin from glial metaplasia of pluripotent Müllerian stem cells residing in the peritoneum or underlying mesenchymal tissue. It is suggested that teratomas with significant glial components secrete factors that induce glial differentiation in these stem cells.

The differential diagnosis for peritoneal tumors is broad and includes both primary and secondary lesions. Secondary involvement by metastasis, heterotopic implantation, systemic diseases (eg sarcoidosis), or infections are most common. Primary peritoneal pathology may be of mesothelial, epithelial, smooth muscle, or uncertain lineage.

Leiomyomatosis peritonealis disseminata, or diffuse peritoneal leiomyomatosis, is a primary peritoneal neoplasm that presents as innumerable smooth muscle nodules. Its exact etiology is not known, although one theory postulates that it arises from subperitoneal mesenchymal stem cell metaplasia secondary to hormonal stimulation. Others suggest that it results from seeding of the peritoneum with benign smooth muscle cells after myomectomy. The nodules in diffuse peritoneal leiomyomatosis can range from a few millimeters to several centimeters in size. Ascites and omental caking are not typically found. It is benign and often incidentally noted during workup of other lesions. Many of these patients have a concurrent history of uterine leiomyoma. The nodules may regress after oophorectomy and can undergo sarcomatous transformation. Microscopically, these nodules are well circumscribed and composed of interlacing fascicles of bland, uniform, spindled smooth muscle cells in a background of omental and fatty tissue. There is no significant atypia or mitotic activity. They stain for desmin, SMA, and caldesmon. They are also usually positive for WT1, ER, and PR and negative for glial markers.

Low-grade endometrioid stromal sarcoma can involve the peritoneum either primarily or from secondary spread. Histologically, in the peritoneum, the characteristic infiltrative pattern is replaced by a multinodular growth pattern. The tumor is composed of monotonous, spindled, endometrial stromal cells with oval nuclei, scant cytoplasm, and minimal atypia that whorl around prominent arterioles. Focally, hyaline plaques or fibromyxoid stroma may be present. Endometrioid stromal sarcoma is readily distinguished from gliomatosis by its immunohistochemical profile, as it is strongly and diffusely positive for ER, PR, and often CD10.  

Ectopic decidua is another entity that can present grossly with numerous 0.2 to 2.0 cm peritoneal nodules. It is often found incidentally during exploratory laparotomy. It is thought to arise from either decidualized endometriotic implants or metaplasia of peritoneal mesenchymal cells under the influence of elevated progesterone levels. It is most closely associated with pregnancy and resolves spontaneously within 6 weeks of delivery. Histologically, these lesions show sheet-like growth of spindled or polygonal cells with abundant eosinophilic cytoplasm, distinct cell borders, bland nuclei, and visible nucleoli. Unlike gliomatosis, the cells are negative for GFAP and positive for hormone receptors.  

1. Which of the following statements about gliomatosis peritonei is true?  
    
   1. It arises from metaplasia of low-grade peritoneal carcinoid lesions.
   2. It is considered a World Health Organization grade 0 lesion.
   3. It is most commonly associated with Brenner tumors.
   4. Lesions are never associated with endometriosis.
   5. Prognosis is poor, as it predicts increased likelihood of metastasis of the primary lesion. 
       
2. Which of the following features excludes a diagnosis of gliomatosis peritonei?  
    
   1. Ascites
   2. Immature neuroepithelial elements
   3. Large mass-forming tumor
   4. Presence of choroid plexus tissue
   5. Presence of endometriosis
3. Which of the following causes of peritoneal nodules is the most common? 
    
   1. Diffuse peritoneal leiomyomatosis
   2. Ectopic decidua
   3. Gliomatosis peritonei
   4. Low-grade endometrioid stromal sarcoma
   5. Secondary involvement by metastases 

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8. Toriyama A, Ishida M, Amano T, et al. Leiomyomatosis peritonealis disseminata coexisting with endometriosis within the same lesions: a case report with review of the literature. Int J Clin Exp Pathol. 2013;6(12):2949-2954.  

1. B- It is considered a World Health Organization grade 0 lesion
2. B- Immature neuroepithelial elements
3. E- Secondary involvement by metastases