Barry M. Shmookler

Disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis. A clinicopathologic analysis of 109 cases with emphasis on distinguishing pathologic features, site of origin, prognosis, and relationship to "pseudomyxoma peritonei".

Pseudomyxoma peritonei (PMP) is a poorly understood condition characterized by mucinous ascites and mucinous implants diffusely involving the peritoneal surfaces. There is considerable debate regarding the definition, pathology, site of origin, and prognosis of PMP. We analyzed the clinicopathologic features of 109 cases of multifocal peritoneal mucinous tumors to develop a pathologic definition of cases characterized by the clinical condition PMP. Cases were separated into two diagnostic categories: disseminated peritoneal adenomucinosis (DPAM) and peritoneal mucinous carcinomatosis (PMCA). Cases classified as DPAM were characterized by peritoneal lesions composed of abundant extracellular mucin containing scant simple to focally proliferative mucinous epithelium with little cytologic atypia or mitotic activity, with or without an associated appendiceal mucinous adenoma. Cases classified as PMCA were characterized by peritoneal lesions composed of more abundant mucinous epithelium with the architectural and cytologic features of carcinoma, with or without an associated primary mucinous adenocarcinoma. Sixty-five of the 109 cases (59.6%) were classified as DPAM consistent with origin from an appendiceal mucinous adenoma. Thirty-seven of the 65 cases (56.9%) had a documented appendiceal mucinous adenoma. Thirty cases (27.5%) were classified as PMCA consistent with origin from an appendiceal or intestinal mucinous adenocarcinoma. Fourteen cases (12.8%) were classified as PMCA with features intermediate between DPAM and PMCA or with discordant features based on the finding of at least focal areas of carcinoma in the peritoneal lesions, whether or not the primary site demonstrated carcinoma. The cases with intermediate features were derived from well-differentiated appendiceal or intestinal mucinous adenocarcinomas and had peritoneal lesions displaying features of DPAM as well as focal areas of mucinous carcinoma. The cases with discordant features were derived from atypical appendiceal adenomas with little or no histologic evidence of a transition from adenoma to carcinoma and had peritoneal lesions uniformly composed of mucinous carcinoma. There was a statistically significant difference in survival between cases classified as DPAM, those classified as PMCA with intermediate or discordant features, and those classified as PMCA (p < 0.0001). The age-adjusted 5-year survival rates were 84% for patients with DPAM, 37.6% for patients with PMCA with intermediate or discordant features, and 6.7% for patients with PMCA. The term DPAM should be used to diagnose the histologically benign peritoneal lesions associated with ruptured appendiceal mucinous adenomas and those that are pathologically identical but lack a demonstrable appendiceal adenoma. Cases with the pathologic features of adenocarcinoma should be designated PMCA because they have recognizably different pathologic features and a significantly worse prognosis.

Patients with pseudomyxoma peritonei associated with disseminated peritoneal adenomucinosis have a significantly more favorable prognosis than patients with peritoneal mucinous carcinomatosis.

Pseudomyxoma peritonei (PMP) is a poorly understood condition characterized by disseminated intraperitoneal mucinous tumors, often with mucinous ascites. The term PMP has been applied historically as a pathologic diagnostic term to both benign and malignant mucinous neoplasms that produce abundant extracellular mucin, resulting in a variable and poorly predictable prognosis. A recent study reported a pathologic classification that separated patients into prognostically distinct groups, but the follow‐up was relatively short.

Pseudomyxoma peritonei in women: A clinicopathologic analysis of 30 cases with emphasis on site of origin, prognosis, and relationship to ovarian mucinous tumors of low malignant potential

Pseudomyxoma peritonei (PMP) is a poorly understood condition characterized by the accumulation of abundant mucinous material within the peritoneal cavity and associated with a mucinous tumor of the gastrointestinal tract or ovaries. Recently there has been considerable debate over the primary site of origin of the tumor associated with PMP in women. Some investigators have proposed a primary site in the ovaries, whereas others favor the gastrointestinal tract or the peritoneum. Another confusing issue has been the nature of the ovarian mucinous tumors associated with PMP. Although these neoplasms may be frankly malignant, more often they show minimal cytologic atypia and epithelial proliferation and have been classified as borderline or low malignant potential tumors. In order to address the issues of site of origin and nature of the associated ovarian mucinous tumors, we studied 68 cases of PMP in women, 30 of whom had mucinous tumors involving the ovaries. All 30 of these cases had an associated mucinous appendiceal or intestinal tumor. The PMP cases with ovarian tumors were compared with 30 ovarian mucinous tumors of low malignant potential (LMP). Based on the analysis of the primary ovarian mucinous LMP tumors, a set of criteria was formulated and used to determine the probable site of origin of PMP in the 30 women with mucinous tumors involving the ovaries. The following gross and microscopic features of the ovarian tumor were considered to be inconsistent with a primary ovarian origin: (1) surface involvement with or without superficial stromal involvement only; (2) adenocarcinoma with signet ring cell differentiation, with a previously diagnosed or concurrent appendiceal tumor of similar morphology; (3) bilateral adenocarcinoma consistent with colonic or appendiceal morphology; and (4) unilateral adenocarcinoma consistent with colonic or appendiceal morphology with a history of a colonic or appendiceal adenocarcinoma. When any one of these features was present the ovarian tumor was diagnosed as secondary. The following additional features also were considered to be more typical of secondary ovarian involvement: (1) normal or only slightly enlarged ovaries; (2) bilateral ovarian involvement; (3) simple or only focally proliferative mucinous epithelium with abundant extracellular mucin in cases with predominantly surface involvement of the ovaries, with or without a history of/or concurrent appendiceal adenoma; (4) multifocal or extensive pseudomyxoma ovarii in cases with stromal involvement, with or without a history of/or concurrent appendiceal adenoma; (5) ruptured appendiceal adenoma and unruptured ovarian tumor of similar histology; and (6) presence of an associated mucinous intestinal tumor.(ABSTRACT TRUNCATED AT 400 WORDS)

Immunohistochemical evidence supporting the appendiceal origin of pseudomyxoma peritonei in women

SummaryWomen with pseudomyxoma peritonei (PMP), characterized by multifocal mucinous implants (disseminated peritoneal adenomucinosis), often have synchronous appendiceal and ovarian mucinous tumors. There has been considerable debate as to whether the ovarian tumors are secondary to the appendiceal tumor or are independent primary ovarian tumors; the latter are usually classified as mucinous tumors of low malignant potential (MLMP). It has been reported that cytokeratins (CK) 7, 18, and 20, carcinoembryonic antigen (CEA). and human alveolar macrophage 56 (HAM-56) are useful markers for distinguishing primary ovarian neoplasms from metastases of intestinal origin. Nearly all primary ovarian MLMP tumors and mucinous carcinomas are positive for CK 7, 18, and 20, CEA, and HAM-56, whereas most colorectal adenocarcinomas are negative for both CK 7 and HAM-56 and positive for CK 20 and CEA. Thirteen appendiceal and 14 ovarian mucinous tumors from 14 cases of PMP and 11 primary ovarian MLMP tumors were studied immunohistochemically for expression of CK 7, 18, and 20, monoclonal and polyclonal CEA (mCEA and pCEA). and HAM-56. Of 14 cases of PMP, 10 (71.4%) had identical staining patterns for all antibodies in both the appendiceal and ovarian tumors. For eight of these, the pattern of immunoreactivity was characterized by negative reactions for CK 7 and HAM-56 and positive reactions for CK 18 and 20. mCEA, and pCEA. One additional case for which only the ovarian tumor could be stained had the same pattern. The remaining two cases were also positive for CK 18 and 20 and CEA. but in addition were positive for CK 7. Two cases were discordant only for CK 7 and one case was discordant for both CK 7 and HAM-56. All 11 MLMP tumors were positive for CK 7 and 18, and pCEA. Eight (72.7%) of 11 were positive for HAM-56, mCEA, and CK 20. There was a statistically significant difference in the frequency of immunoreactivity for CK 7 (p = 0.0005) and HAM-56 (p = 0.0002) between the ovarian mucinous tumors in PMP and the MLMP tumors, with the ovarian tumors in PMP tending to be negative for CK 7 and HAM-56. similar to the appendiceal adenomas. Most ovarian mucinous tumors in PMP demonstrate a pattern of immunoreactivity with CK 7, 18, and 20, CEA, and HAM-56 that is identical to the associated appendiceal adenoma and distinct from primary ovarian MLMP tumors, consistent with the interpretation that these ovarian tumors are secondary to the appendiceal tumor.

Giant cell fibroblastoma. A juvenile form of dermatofibrosarcoma protuberans

A clinicopathologic analysis of 28 cases of giant cell fibroblastoma (GCF), a rare mesenchymal tumor occurring predominantly in the first decade of life, is presented. This disease presented as a painless, slowly enlarging, subcutaneous mass. The tumor recurred locally in 47% of the patients; however, metastasis was not detected. On microscopic examination, GCF showed an unique combination of spindle cell patterns, pleomorphic and multinucleated giant cells, myxoid areas, and distinctive sinusoid‐like spaces. This unrecognized histomorphologic picture led to a misdiagnosis of sarcoma in 40% of the cases. The histogenesis of this lesion remains uncertain; however, based on both clinical and morphologic similarities, it is proposed that GCF is a juvenile form of dermatofibrosarcoma protuberans (DFSP).

The morphologic spectrum of ovarian metastases of appendiceal adenocarcinomas : A clinicopathologic and immunohistochemical analysis of tumors often misinterpreted as primary ovarian tumors or metastatic tumors from other gastrointestinal sites

Twenty cases of ovarian metastases derived from appendiceal adenocarcinomas were analyzed. The most common presentation was a pelvic mass. The appendiceal and ovarian tumors were diagnosed concurrently in 15 cases; in the remaining five, the ovarian tumors were diagnosed before the appendiceal tumor. The appendiceal adenocarcinomas demonstrated four morphologic patterns: 1) signet ring cell type, with or without glandular or goblet cell differentiation (14 cases); 2) mixed signet ring cell and intestinal type (two cases); 3) intestinal type (two cases); and 4) typical colorectal type (two cases). The ovarian tumors were bilateral in 16 cases and were histologically similar to the associated appendiceal tumor in each case. Ovarian metastases that demonstrate signet ring cell, glandular, and goblet cell differentiation mimic metastases from gastric adenocarcinoma. Those that are derived from well-differentiated mucinous appendiceal adenocarcinomas mimic primary ovarian mucinous tumors and metastases from the pancreas and biliary tract. Metastases of appendiceal adenocarcinomas of colorectal type simulate both metastatic colorectal carcinoma and primary ovarian endometrioid carcinomas. The appendiceal and ovarian tumors were immunophenotypically identical in each case. Approximately 50% of the appendiceal and ovarian tumors were positive for cytokeratin 7 (CK 7), and all were positive for cytokeratin 20 (CK 20). CK 20 positivity of the ovarian tumors is consistent with gastrointestinal origin; CK 7 positivity does not confirm ovarian origin, because appendiceal carcinomas are positive in 50% of cases. Metastatic appendiceal adenocarcinoma should be considered in the differential diagnosis of mucinous ovarian tumors with signet ring cell, goblet cell, or intestinal type differentiation, especially when these tumors are associated with extraovarian disease and are bilateral.

Fibrosarcomatous change in dermatofibrosarcoma protuberans

This report describes six patients with dermatofibrosarcoma protuberans (DFSP) that contained fibrosarcomatous areas (FS). The clinical signs and symptoms, ages of the patients, and anatomic distribution of the tumors were similar to those of uncomplicated DFSP. FS was concentrated in the subcutis in each case and comprised more than 50% of the tumor in four cases. The characteristic storiform cellular arrangement of DFSP was replaced by long, gently sweeping fascicles of spindle cells that intersected at various angles, forming the so-called herringbone pattern. Trapped fat cells, characteristic of DFSP when it infiltrates subcutaneous tissue, were absent in five of the six FS and only focally present in one. Two FS were grade 1; their cytologic features were similar to those of DFSP. Four FS were grade 2 and had cytologic atypia exceeding that of DFSP. There was a statistical difference between the mitotic rates of DFSP and FS. Five patients were alive and well at the time of last follow-up (median, 2 years), and one patient had an unexcised recurrence when last examined. Six similar cases from the literature are reviewed; in one of them, the FS metastasized.

Aggressive (malignant?) epithelial odontogenic ghost cell tumor

Although the calcifying odontogenic cyst (COC) is a well-established pathologic entity, it has been recognized that there is an odontogenic neoplasm with histologic features similar to the COC that has often been diagnosed as COC. Investigators have applied several terms to this neoplasm, but we prefer the term epithelial odontogenic ghost cell tumor (EOGCT). No reports have appeared previously in the literature describing either carcinoma arising in a COC or malignant EOGCT. Three cases are reported here with aggressive growth and histologic features strongly implying a malignant potential, although none is known to have metastasized. Two occurred in the maxilla and one in the mandible. One was discovered 9 years following removal of a typical COC, and another recurred rapidly after excision.

Peritoneal carcinomatosis from appendiceal cancer: Results in 69 patients treated by cytoreductive surgery and intraperitoneal chemotherapy

Sixty-nine patients presenting over a 10-year period with peritoneal carcinomatosis from appendiceal cancer were treated with cytoreductive surgery combined with intraperitoneal chemotherapy. The three-year survival is 89.5 percent in patients (38/69) with pseudomyxoma peritonei, 34.5 percent in patients (25/69) with cystadenocarcinoma, and 38.1 percent in patients (6/69) with adenocarcinoma (P<0.01). In this study, a classification of residual disease following the cytoreductive surgery was used. The prognosis of the patients with minimal residual disease was better than that of those with moderate or gross disease, showing a 91.6 percent three-year survival compared with 47.8 percent and 20 percent, respectively (P<0.01). The patients without lymphatic or hematogenous metastases had a better three-year survival than those with metastases (75.1 percentvs.28.6 percent;P<0.01). These findings suggest that peritoneal carcinomatosis from appendiceal cancer can be treated with long-term disease-free survival. The patients with low malignant potential cancer, complete cytoreduction, and no metastases showed the most effective disease control.

Biopsy of musculoskeletal tumors. Current concepts.

Biopsy is a key step in the diagnosis of bone and soft tissue tumors. An inadequately performed biopsy may fail to allow proper diagnosis, have a negative impact on survival, and ultimately necessitate an amputation to accomplish adequate margins of resection. Poorly performed biopsy remains a common finding in patients with musculoskeletal tumors who are referred to orthopaedic oncology centers. The principles by which an adequate and safe biopsy of musculoskeletal tumors should be planned and performed are reviewed, and the surgical approach to different anatomic locations is emphasized.