Histopathologic study of thin vulvar squamous cell carcinomas and associated cutaneous lesions: a correlative study of 48 tumors in 44 patients with analysis of adjacent vulvar intraepithelial neoplasia types and lichen sclerosus.

A series of 48 excised thin (

Progression of simplex (differentiated) vulvar intraepithelial neoplasia to invasive squamous cell carcinoma: a prospective case study confirming its precursor role in the pathogenesis of vulvar cancer.

This prospective case study documents the development of invasive squamous cell carcinoma (SCC) almost 40 months after initial diagnosis and treatment by wide local excision of squamous vulvar intraepithelial neoplasia (VIN) of simplex (or differentiated) type. A 52-year-old woman had no history of a prior or synchronous SCC, nor did she have lichen sclerosus. Simplex VIN involved the margin of the excision specimen, leading to local recurrences and progression into invasive SCC of the conventional keratinizing type. This study conclusively demonstrates that simplex VIN is a distinct type of squamous intraepithelial carcinoma (ie, carcinoma in situ) and a direct precursor of keratinizing SCC.

Borderline epithelial tumors of the ovary.

The concept and terminology of borderline epithelial tumors of the ovary have been controversial for over a century, in spite of the acceptance of a borderline category in almost all current classifications of ovarian tumors. Typically, borderline tumors are noninvasive neoplasms that have nuclear abnormalities and mitotic activity intermediate between benign and malignant tumors of similar cell type. Borderline tumors of all surface epithelial cell types have been studied. The most common and best understood are serous borderline tumors and mucinous borderline tumors of intestinal type, which are the subject of this review. Some of the most challenging issues for serous tumors include: the criteria and clinical behavior of stromal microinvasion; the high prevalence of synchronous extraovarian disease; the classification and histopathologic features of associated peritoneal tumor implants, especially invasive implants; and, the prognostic significance of micropapillary tumors. The mucinous borderline tumors of intestinal type have a different set of considerations, including: their frequently heterogeneous composition with coexisting benign, borderline and malignant elements; the classification and significance of accompanying noninvasive carcinoma; the recognition of stromal invasion, including microinvasion and expansile invasion; and, the historically misunderstood relationship to pseudomyxoma peritonei. All of these issues are discussed in this presentation, as are the important gross and microscopic features of serous and mucinous borderline tumors and pertinent information on their treatment and prognosis.

Diagnostic challenge of secondary (metastatic) ovarian tumors simulating primary endometrioid and mucinous neoplasms.

Secondary (metastatic) neoplasms to the ovary often cause diagnostic problems, especially those tumors that produce large, symptomatic ovarian tumors that masquerade clinically and pathologically as primary ovarian tumors of surface epithelial type. Most of these tumors arise from organs of the digestive system. Except for typical Krukenberg tumors, which usually originate in the stomach and generally are easily recognized, the most diagnostically problematic secondary ovarian tumors are those that originate in the large intestine, appendix, and pancreas. Metastases from these sites typically produce histologic patterns resembling primary ovarian endometrioid carcinoma or mucinous epithelial neoplasms of borderline and malignant types. This review focuses on the diagnostic challenge of distinguishing these secondary ovarian tumors from primary ovarian neoplasms. Studies on useful or potentially applicable immunohistochemical stains are also detailed.

Mucinous tumors of the ovary: a review.

Mucinous ovarian tumors are among the most difficult ovarian neoplasms for surgical pathologists to interpret. Approximately 20% of primary ovarian mucinous tumors are borderline tumors, noninvasive (intraglandular; intraepithelial) carcinomas, or invasive carcinomas; the remainder are cystadenomas. The borderline tumors may be of intestinal type or mullerian (endocervical-like) type. The intestinal-type tumors are by far the most common. Their frequently heterogeneous composition with coexisting elements of cystadenoma, stromal microinvasion, noninvasive carcinoma, and invasive carcinoma requires careful gross examination and extensive sampling of the tumors. The inherent glandular complexity of proliferating mucinous tumors complicates recognition of stromal invasion. Some mucinous carcinomas with expansile (confluent) invasion may be very difficult to discriminate from extensive noninvasive carcinoma. Interobserver reproducibility probably requires use of an arbitrary minimum size criterion for the diagnosis of expansile invasion. Primary invasive carcinomas with an infiltrative growth pattern are less common. Rarely, distinct mural nodules of reactive or neoplastic type are found in the cystic wall of a mucinous tumor. Pseudomyxoma peritonei almost never results from a ruptured primary ovarian mucinous neoplasm, but often produces secondary borderline-like ovarian tumors with prominent pseudomyxoma ovarii. Prognosis of mucinous tumors is highly dependent on stage and histologic composition. Borderline tumors, noninvasive carcinomas, microinvasive tumors, and invasive carcinomas with an expansile growth pattern are generally stage I and have an excellent prognosis with only occasional examples of metastatic spread. Invasive carcinomas with an infiltrative growth pattern are more aggressive, accounting for almost all high-stage mucinous tumors, and are responsible for most deaths caused by tumor. A high index of suspicion that a mucinous tumor is actually a metastasis from another organ is required by pathologists and gynecologists to prevent misdiagnosis of a metastatic neoplasm as a primary ovarian tumor. Secondary mucinous tumors are significantly more often bilateral, <10 cm in maximal dimension, and of high stage. Numerous immunohistochemical stains proposed to aid in the differential diagnosis of primary vs. secondary mucinous tumors also are reviewed.

Müllerian papilloma of the cervix in a child with multiple renal cysts.

An 18-month-old girl was referred for evaluation of vaginal bleeding and a renal mass. Ultrasonography and computed tomography revealed multiple simple cysts within the left kidney and a normal right kidney. At vaginoscopy, a 1-cm frond-like papillary lesion overlying the cervix was identified. The pathologic diagnosis was mullerian papilloma, a rare benign tumor of the vagina and uterine cervix. None of the approximately 40 previously reported cases have been associated with renal anomalies, despite the historical classification of these lesions as mesonephric papillomas. We report the first patient with both a renal anomaly and mullerian papilloma of the uterine cervix.

Symposium part II: special types of adenocarcinoma of the uterine cervix.

This report provides a comprehensive review of several special types of adenocarcinoma of the uterine cervix. The clinicopathologic features of three tumors that may cause difficulties in diagnosis are detailed: adenoid basal carcinoma (epithelioma), adenoma malignum (minimal deviation adenocarcinoma), and mesonephric adenocarcinoma. Updated information on classification and clinical behavior are presented, as is data on their histochemical, immunohistochemical, and molecular profiles.

Uterine artery embolization of leiomyomas with trisacryl gelatin microspheres (TGM): pathologic features and comparison with polyvinyl alcohol emboli.

In recent years, uterine artery embolization (UAE) has gained popularity as an alternative to surgery for the treatment of symptomatic uterine leiomyomas. Polyvinyl alcohol (PVA) particles have been the principal agent used for UAE. Recently, trisacryl gelatin microspheres (TGM) have been advocated as a preferable occlusive material for UAE. It is the first embolic agent to be cleared specifically by the United States Food and Drug Administration for this use. To date, information on the tissue effects, distribution, and morphology of UAE with TGM in resected human organs is very limited. Herein, we document the pathologic findings in a 46-year-old woman who underwent hysterectomy and bilateral salpingo-oophorectomy and omentectomy for metastatic colonic adenocarcinoma 19 months after UAE with TGM (microsphere size = 500-700 micron) for uterine leiomyomas. Histologically, a submucosal leiomyoma and an intramural uterine leiomyoma showed massive coagulative necrosis of the infarct-type with a peripheral zone of hyalinized fibrous tissue. Aggregates of TGM were within the necrotic leiomyomas and throughout the myometrium. Non-targeted extrauterine sites also contained TGM, including the paracervical soft tissue and the mesosalpinx as well as the ovaries and omentum where they were adjacent to metastatic colonic carcinoma. Other than the myomas, none of the embolized organs showed ischemic necrosis. Although some TGM were intravascular, most were extravascular. Typically, the microspheres were adjacent to muscular arteries from which they appeared to have been extruded following localized dissolution of the arterial wall. A thin rim of foreign body-type giant cells and mononuclear macrophages surrounded many of the TGM and focally involved the arterial wall. No vascular thrombosis was seen. TGM are believed to have advantages over PVA emboli for UAE. Hence, additional examples of surgical specimens following treatment of leiomyomas with TGM can be expected. Pathologists should be aware of the morphology of TGM in resected genital tract tissues. Although TGM are easily distinguished from embolic PVA particles, they may be mistaken for PVA microspheres if not carefully studied. Elastic stains are useful in the differential diagnosis of embolic agents.

Pagetoid squamous cell carcinoma in situ (pagetoid Bowen's disease) of the external genitalia.

Approximately 5% of cutaneous squamous cell carcinomas in situ (SCCIS) have a nested pattern, referred to as pagetoid SCCIS, or pagetoid Bowen's disease. This growth pattern may simulate extramammary Paget's disease (EPD) when the external genitalia are involved. We report two cases of genital pagetoid SCCIS, including the first example affecting the vulva. Using several known cases each of classic (bowenoid) SCCIS of the vulva, primary cutaneous vulvar EPD, and cutaneous melanoma in situ as controls, we performed a battery of immunohistochemical and mucin stains to study the phenotype of pagetoid SCCIS. Both cases of pagetoid SCCIS were strongly positive for cytokeratin (CK) 7, a highly sensitive and popular marker for EPD. Stains with the high molecular weight cytokeratin marker Keratin-903 (34betaE12) showed 4+ immunoreactivity, although not with the intensity seen in the juxtaposed normal keratinocytes or in the cells of classic SCCIS. Immunoreactivity scores were 2+ for CK5/6, 2+ for CK19, and 1+ to 3+ for CK 13. Unlike the Paget's cells of EPD, the nested cells of pagetoid SCCIS were devoid of mucin and were nonimmunoreactive with GCDFP-15, CEA, CAM5.2, and c-erbB2. Stains for CK20, S-100, and Melan A also were negative. Although CK7 is a sensitive marker for the Paget's cells of EPD, this study corroborates the unexpected CK7 positivity in pagetoid SCCIS, precluding its usefulness in distinguishing these two diseases. Combined with mucin stains, a limited immunohistochemical panel may be of diagnostic value in particularly difficult cases.

Genital tract tumors in Proteus syndrome: report of a case of bilateral paraovarian endometrioid cystic tumors of borderline malignancy and review of the literature.

Proteus syndrome is a rare, sporadic disorder that causes postnatal overgrowth of multiple tissues in a mosaic pattern. Characteristic manifestations include: overgrowth and hypertrophy of limbs and digits, connective tissue nevus, epidermal nevus and hyperostoses. Various benign and malignant tumors and hamartomas may complicate the clinical course of patients with the syndrome. Commonly encountered tumors include hemangiomas, lymphangiomas and lipomas. Tumors of the genital tract occur less often. Bilateral ovarian cystadenomas are regarded as having diagnostic value in Proteus syndrome when occurring within the first two decades of life. We describe a 3-year-old girl with Proteus syndrome who developed bilateral paraovarian villoglandular endometrioid cystadenomatous tumors of borderline malignancy (low malignant potential) of the broad ligament. Desmoplastic tumor implants, presumably noninvasive, were present in biopsies from the pelvic floor, cul-de-sac and omentum. This is the first recognized example of a cystic borderline epithelial tumor of the female genital tract and the first paraovarian tumor reported in a patient with Proteus syndrome. Previously reported tumors and cystic lesions involving the female genital tract and the male genital tract in patients with Proteus syndrome are reviewed. We suspect that specific testicular and paratesticular tumors may prove to have the same diagnostic value in Proteus syndrome as do bilateral cystic ovarian and paraovarian tumors.