Selected topics in peritoneal pathology.

This essay considers selected peritoneal lesions many of which were the subject of studies coauthored by Dr Robert E. Scully. His article on multilocular peritoneal inclusion cysts has largely led to these lesions being considered non-neoplastic, eschewing the term cystic mesothelioma. These cysts are often associated with reactive mural mesothelial proliferations that can potentially lead to a misdiagnosis of mesothelioma. Clinical findings, such as a common association with endometriosis or prior operations, can prompt consideration of a reactive lesion. Mesothelial hyperplasia may be difficult to distinguish, when florid, from mesothelioma but a variety of gross and microscopic features will aid their recognition. Nodular peritoneal aggregates of histiocytes (sometimes admixed with mesothelial cells) may occasionally be a striking finding that can be misdiagnosed as a metastasis if the patient has a known neoplasm. Appreciation of their bland nuclear features and histiocytic nature, confirmed by immunohistochemical markers, facilitate the diagnosis. Various forms of peritonitis are briefly considered including sclerosing peritonitis, a process sometimes associated with luteinized thecomas (thecomatosis) of the ovaries, an entity first appreciated by Dr Scully. Mesotheliomas are briefly reviewed emphasizing the caution that should be used in applying the designation "well-differentiated papillary mesothelioma." Many interpret the latter as benign, but multifocal lesions must be thoroughly examined histologically because of potential overlapping features with malignant mesothelioma. The morphologic spectrum of malignant mesothelioma and its usually straightforward distinction from müllerian neoplasms is considered, as is its occasional presentation as a dominant ovarian mass. The spectrum of low-grade serous peritoneal neoplasms including the "psammocarcinoma" is reviewed. Finally, various benign müllerian lesions, particularly endometriosis and endosalpingiosis, may be conspicuous in peritoneal specimens and sometimes are grossly striking. The usual presence of benign endometrioid epithelium and stroma should facilitate the correct diagnosis of endometriosis, but in cases in which the stroma is atrophic or the sole component (stromal endometriosis), diagnostic problems may arise.

Diagnosis of ovarian carcinoma cell type is highly reproducible: a transcanadian study.

Reproducible diagnosis of ovarian carcinoma cell types is critical for cell type-specific treatment. The purpose of this study was to test the reproducibility of cell type diagnosis across Canada. Analysis of the interobserver reproducibility of histologic tumor type was performed among 6 pathologists after brief training in the use of modified World Health Organization criteria to classify ovarian carcinomas into 1 of 6 categories: high-grade serous, endometrioid, clear cell, mucinous, low-grade serous, and other. These 6 pathologists independently reviewed a test set of 40 ovarian carcinomas. A validation set of 88 consecutive ovarian carcinomas drawn from 5 centers was subject to local review by 1 of the 6 study pathologists, and central review by a single observer. Interobserver agreement was assessed through calculation of concordance and kappa values for pair-wise comparison. For the test set, the paired concordance between pathologists in cell type diagnosis ranged from 85.0% to 97.5% (average 92.3%), and the kappa values were 0.80 to 0.97 (average 0.89). Inclusion of immunostaining results did not significantly improve reproducibility (P=0.69). For the validation set, the concordance between original diagnosis and local review was 84% and between local review and central review was 94%. The kappa values were 0.73 and 0.89, respectively. With a brief training exercise and the use of defined criteria for ovarian carcinoma subtyping, there is excellent interobserver reproducibility in diagnosis of cell type. This has implications for clinical trials of subtype-specific ovarian carcinoma treatments.

Endometrial/ioid Stromal Tumors and Related Neoplasms of the Female Genital Tract.

Endometrial/ioid stromal tumors comprise a spectrum of mesenchymal neoplasms, ranging from benign to low-grade malignancy to undifferentiated sarcomas, which occur predominantly in the uterus but may rarely originate at extrauterine sites, most commonly in the ovary. These tumors and their morphologic variants are important to recognize as they often cause diagnostic difficulties. This review focuses on the diagnostic criteria and differential diagnosis, including the role of immunohistochemistry.

Unusual morphologic features of endometrial stromal tumors: a report of 2 cases.

Endometrial stromal tumors with typical morphology usually do not pose diagnostic problems. However, the finding of unusual morphologic features may be misleading in the final interpretation of these tumors. Herein, we described two endometrial stromal sarcomas discovered in hysterectomy specimens of women 31 and 75 years of age. Features typical of endometrial stromal neoplasia were present in both cases. Additionally, in 1 case, extensive fatty metaplasia as well as smooth and skeletal muscle metaplasia were found; and in the second case, focal bizarre nuclei, smooth muscle differentiation, and fibrous change were present. The differential diagnosis in the first case included cellular intravenous leiomyomatosis/lipoleiomyomatosis with skeletal muscle differentiation; and in the second case, a cellular smooth muscle tumor with bizarre nuclei was considered.

Malignant peritoneal mesothelioma in women: a study of 75 cases with emphasis on their morphologic spectrum and differential diagnosis.

Seventy-five malignant mesotheliomas of the peritoneum in women were reviewed to highlight their morphologic spectrum. The patients ranged from 17 to 92 (mean, 47.4) years of age. The clinical presentation was usually abdominal or pelvic pain, abdominal swelling (sometimes due to ascites), or a pelvic mass. On microscopic examination, the majority of the tumors had only an epithelial morphology, but 4 were biphasic and 1 was sarcomatoid. The most common epithelial patterns were tubular and papillary (which often coexisted), but 5 tumors were purely diffuse; 2 had cells with abundant glassy eosinophilic cytoplasm (so-called deciduoid mesothelioma). The cells in the tubular and papillary patterns were generally cuboidal with scant to moderate amounts of eosinophilic cytoplasm. Nuclear atypia was usually only mild, although a minority of cases had moderate or even, occasionally, severe atypia. Many tumors had foci that, viewed in isolation, resembled so-called well-differentiated papillary mesothelioma, and accordingly that diagnosis should be made cautiously. Unusual features were lymphoid follicles (13 cases), striking myxoid stroma (5 cases), prominent foamy histiocytes (5 cases), and a striking vascular proliferation (1 case). The varied morphology of peritoneal malignant mesotheliomas may raise a broad differential diagnosis, but in most cases the resemblance to other tumors is limited. Histochemistry, immunohistochemistry, and electron microscopy may provide important aid, particularly when tissue is limited, but should be needed only occasionally.

Immunohistochemistry as a tool in the differential diagnosis of ovarian tumors: an update.

Immunohistochemistry has become an important tool in the diagnosis of ovarian tumors. This article reviews the role of immunohistochemistry in the differential diagnosis of the three main categories of ovarian tumors, with emphasis on recently developed antibodies. In the surface epithelial stromal category the most common problem is its discernment from metastasis. The use of differential cytokeratins, primarily CK7 and CK20, as well as Cdx-2, beta-catenin, and P504S in differentiating between metastatic adenocarcinoma, particularly of colorectal origin, and primary ovarian carcinoma is discussed. Dpc4 may be useful in distinguishing pancreatic from ovarian mucinous carcinomas, because up to 55% of pancreatic carcinomas lack Dpc4 expression, whereas the differential expression of mucin genes may be helpful in distinguishing between primary ovarian mucinous and metastatic tumors. Urothelial markers (thrombomodulin and uroplakin III) and renal cell carcinoma markers (CD10 and renal cell carcinoma marker) can be helpful in the diagnosis of metastatic urothelial and renal cell tumors to the ovary. The roles of inhibin, calretinin, CD99, and other recently described markers in the diagnosis of sex cord-stromal tumors are reviewed. The uses of OCT-4 (POU5F1) (a new highly sensitive and specific marker of dysgerminoma and embryonal carcinoma), CD30, and c-kit are also discussed.

Superficial endometriosis of the cervix: A source of abnormal glandular cells on cervicovaginal smears.

Superficial endometriosis of the cervix, a benign process which may be associated with atypical glandular cells of undetermined significance (AGUS) on cervicovaginal (CV) smears, is becoming increasingly recognized on colposcopic examination. This study details the clinical, cytologic, and histology features of six cases of superficial cervical endometriosis. All CV smears featured atypical endocervical-like columnar cells in sheets and strips as well as cells with endometrial characteristics including solid cohesive, crowded, overlapping glandular groups, loss of cellular polarity, and a frequent ragged "feathered" edge appearance with protruding nuclei, occasional rosette formations, and endometrial stroma. Recognition of endometrial stroma in continuity with groups of cells with these features on CV smears may suggest the diagnosis of this benign condition. However, the cytologic features of endometriosis show sufficient overlap with those of precancerous and cancerous glandular lesions that many of these cases will continue to be diagnosed as "atypical glandular cells."

Brenner tumor of the ovary with striking microcystic change.

An ovarian Brenner tumor from a 39-year-old woman exhibited striking microcystic change that was so extensive it largely obscured the nature of the tumor, causing initial diagnostic difficulty. The patient presented with symptoms related to a pelvic mass and had a unilateral, 24 cm in maximal dimension, stage I tumor that was solid and cystic. Microscopic examination revealed extensive microcystic change within the epithelial nests in large areas of the tumor such that transitional-type epithelium was only recognized very focally. The tumor had minor areas (<5%) that showed marked cytological atypia and mitotic activity, interpreted as microscopic foci of intraepithelial carcinoma, but was predominantly benign. The presence of characteristic fibromatous stroma and mucinous metaplasia within the epithelial nests provided important clues to the correct diagnosis.

Ovarian teratomas with florid benign vascular proliferation: a distinctive finding associated with the neural component of teratomas that may be confused with a vascular neoplasm.

Prominent benign vascular proliferations associated with neural tissue in five cases of ovarian teratoma are described. The ages of the patients ranged from 15 to 35 years. Three of the five had tumors confined to the ovary, one had peritoneal implants, and one had widespread metastatic immature teratoma. Two of the patients are alive and well, 8 and 9 years postoperatively. Follow-up is unavailable in two cases and the final case was recent. The tumor in three of the cases had features of mature cystic teratoma including abundant mature neural tissue and, in one instance, microscopic foci of primitive neuroepithelium. The tumor in the fourth case was an immature teratoma with abundant primitive neuroepithelium, and in the fifth case was a mixed germ cell tumor, composed mostly of immature teratoma with a minor component of yolk sac tumor. In all the tumors there was a prominent vascular proliferation composed of long thin-walled, curved vessels or a solid glomeruloid arrangement. Immunohistochemistry done in two cases confirmed the vascular nature of the proliferation. Angiogenesis, likely as an expression of vascular endothelial growth factors, is a well-known phenomenon in a variety of neural and neuroendocrine neoplasms, in particular high-grade gliomas. However, very few cases of this phenomenon have been described in association with neural tissue in the ovary. Recognition of this proliferation as a benign secondary one is important to avoid misdiagnosis of a vascular neoplasm or an immature teratoma, as happened in one of our cases.