Molecular genetic analysis of appendiceal mucinous adenomas in identical twins, including one with pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is a clinical syndrome characterized by mucinous ascites and peritoneal lesions composed of histologically bland to low-grade adenomatous mucinous epithelium within pools of extracellular mucin, often with an associated mucinous adenoma of the appendix. There is evidence that the peritoneal lesions in PMP are clonally derived from the associated appendiceal adenoma. Little is known about the molecular genetic alterations or hereditary factors involved in the development of appendiceal mucinous tumors and PMP. We report the only known example of appendiceal mucinous adenomas in identical twin brothers, one of whom developed PMP. We analyzed the status of the K-RAS and APC genes in these tumors using digital polymerase chain reaction and digital single nucleotide polymorphism (SNP) assay. Identical K-RAS mutations were detected in the appendiceal adenoma and peritoneal tumor from the twin with PMP, whereas the adenoma from the other twin harbored a different mutation. Digital SNP analysis demonstrated loss of heterozygosity of APC only in the adenoma from the twin without PMP but not from the appendiceal or peritoneal tumors of the twin with PMP. The adjacent normal tissue in each case retained both APC alleles. The K-RAS mutational analysis supports the view that PMP is clonally derived from the associated appendiceal mucinous adenoma. The lack of loss of heterozygosity of APC in the adenoma and peritoneal tumor from the twin with PMP suggests that loss of heterozygosity of APC is not necessarily involved in the development of all appendiceal adenomas or PMP. The different types of mutations in K-RAS and the different allelic status of the APC locus in the tumors from both twins suggest that mutation in K-RAS and loss of heterozygosity of APC occurs somatically in adenomas and is independent of the identical genetic background of the twins.

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

BACKGROUND: 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. METHODS: Long-term follow-up data were analyzed for a previously reported series of 109 patients with PMP to examine the prognostic utility of a pathologic classification system that divided patients into three groups: disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and peritoneal mucinous carcinomatosis with intermediate or discordant features (PMCA-I/D). Patients whose tumors were classified 25 DPAM (n = 65 patients) had disease that was characterized by histologically bland to low-grade adenomatous mucinous epithelium associated with abundant extracellular mucin and fibrosis, often with an identifiable appendiceal mucinous adenoma that was the source of the peritoneal lesions. Patients whose tumors were classified 25 PMCA (n = 30 patients) had disease that was characterized by peritoneal lesions that displayed the cytologic and architectural features of mucinous carcinoma associated with extracellular mucin, often with an identifiable invasive mucinous adenocarcinoma of the gastrointestinal tract. Patients whose tumors were classified 25 PMCA-I (n = 11 patients) had peritoneal lesions that combined the features of DPAM and PMCA derived from well differentiated mucinous adenocarcinomas associated with adenomas. Patients whose tumors were classified 25 PMCA-D (n = 3 patients) had markedly atypical appendiceal adenomas associated with peritoneal lesions similar to PMCA. RESULTS: Patients with DPAM had 5-year and 10-year survival rates of 75% and 68%, respectively (mean follow-up, 96 months; median follow-up, 104 months). Patients with PMCA and PMCA-I/D had a significantly worse prognosis, with 5-year and 10-year survival rates, respectively, of 50% and 21% for PMCA-I/D (mean follow-up, 58 months; median follow-up, 51 months) and 14% and 3% for PMCA (mean follow-up, 27 months; median follow-up, 16 months; P = 0.0001). CONCLUSIONS: The term PMP should be used only as a clinical descriptor for patients who have the syndrome of mucinous ascites accompanied by a characteristic distribution of peritoneal mucinous tumors with the pathologic features of DPAM. DPAM should be used as a pathologic diagnostic term for patients with the bland peritoneal mucinous tumors associated with ruptured appendiceal mucinous adenomas and PMP. These patients should not be diagnosed with carcinoma, because they have disease that is distinct pathologically and prognostically from PMCA.

Survival after induction chemotherapy and surgical resection for high-grade soft tissue sarcoma. Is radiation necessary?

BACKGROUND: Induction chemotherapy can produce dramatic necrosis in sarcomas-raising the question of whether or not radiation is necessary. This study reviews the clinical outcome of a subset of patients with high-grade extremity soft tissue sarcomas (STS) who were treated with induction chemotherapy and surgical resection but without radiation. METHODS: Nonmetastatic, large, high-grade STS of the pelvis and extremities were treated with intra-arterial cisplatin, adriamycin, and, after 1995, ifosfamide. After induction, oncologic resection and histologic evaluation were performed. Good responders with good surgical margins were not treated with radiation. RESULTS: Thirty-three patients, with a median follow-up of 5 years, were included. Limb salvage rate was 94%. Median tumor necrosis was 95%. Four patients developed metastatic disease with three subsequent deaths. Two local recurrences occurred; both patients were salvaged with reresection and adjuvant external beam radiotherapy, although one died of metastatic disease 10 years later. Relapse-free and overall survival is 80% and 88% at 5 and 10 years by Kaplan-Meier analysis. CONCLUSIONS: Intensive induction chemotherapy can be extremely effective for high-grade STS, permitting limb-sparing surgery in lieu of amputation. Radiation may not be necessary if a good response to induction chemotherapy and negative wide margins are achieved. All patients with large, deep, high-grade STS of the extremities should be considered candidates for induction chemotherapy.

Peritoneal carcinomatosis from an unknown primary site. Management of 15 patients.

AIMS AND BACKGROUND: Peritoneal carcinomatosis from an unknown primary site is a rare and ill-defined entity. This work attempts to identify clinical and pathological features of patients with this disease and report the results of an aggressive combined treatment modality. METHODS: Retrospective analysis was performed of medical records of 15 patients with peritoneal carcinomatosis with no primary site identified at a single institution between 1989 and 2000. A primary gastrointestinal cancer was ruled out after a thorough endoscopic and radiologic work-up and complete exploratory surgery. RESULTS: Four women and 11 men were identified; the average age was 49 years. All patients had cytoreductive surgery with peritonectomies; 4 patients underwent a second-look operation. Perioperative intraperitoneal chemotherapy was given to 10 of the 15 patients, and 9 patients received post-cytoreduction chemotherapy given intraperitoneally (1), systemically (7) or both intraperitoneally and systemically (1). Overall median survival from diagnosis was 19.0 months; 1 patient is alive with disease at 21 months; and 3 patients are disease-free at 17, 38, and 60 months from diagnosis. Significant positive predictive factors for survival were a small volume of ascites (P = 0.02), a large number of peritonectomies performed (P = 0.001), second-look cytoreduction (P = 0.003), perioperative intraperitoneal chemotherapy (P = 0.008) and postoperative chemotherapy (P= 0.01), either intraperitoneal or systemic. CONCLUSIONS: Peritoneal carcinomatosis from an unknown primary site is a rare subset of primary peritoneal malignancy. Aggressive treatment may provide prolonged palliation with occasional long-term survival.

Histopathologic analysis in 46 patients with pseudomyxoma peritonei syndrome: failure versus success with a second-look operation.

Pseudomyxoma peritonei syndrome is a disease characterized by mucinous ascites and mucinous tumor disseminated on peritoneal surfaces; the disease almost always originates from a perforated appendiceal epithelial tumor. Histopathologic assessment of aggressive versus noninvasive character of the mucinous tumor has been shown to have an impact on survival in patients treated with cytoreductive surgery and intraperitoneal chemotherapy. Out of a database of 312 patients having a complete cytoreduction for pseudomyxoma peritonei syndrome, 46 patients (24 male and 22 female) had at least one second-look surgery. Before this review, all 46 of these patients were clinically uniformly categorized with a diagnosis of pseudomyxoma peritonei. Using the criteria described by Ronnett and colleagues, all specimens from the multiple surgical procedures performed on these patients were reviewed and reclassified as disseminated peritoneal adenomucinosis (adenomucinosis), adenomucinosis/mucinous adenocarcinoma (hybrid), or mucinous adenocarcinoma. The review was performed in a blinded fashion by a single pathologist (HY). To facilitate a critical evaluation of these histopathologic assessments, the patients were separated into two groups: (1) 19 patients who had a second-look surgery that was unsuccessful in that they went on to die of their disease or in that they currently have disease progression and a limited survival and (2) 27 patients who had a successful second look and currently continue disease free with a minimum 3-year follow-up period. As a result of this review, 11 of 19 patients with an unsuccessful second look and originally designated pseudomyxoma peritonei were reclassified as hybrid-type malignancy (four patients) or mucinous adenocarcinoma (seven patients). Only two patients were reclassified in the successful second-look group (P =.0005). Transitions from a less aggressive to a more invasive histology from one cytoreduction to the next occurred on 13 occasions in patients whose second-look surgery failed and in one patient with a successful second-look surgery (P <.0001). Seven patients retained a histologic classification of disseminated peritoneal adenomucinosis but went on to die of an aggressive disease process. Clinical assessments suggested that failure of second-look surgery for pseudomyxoma peritonei was associated with a biologically more aggressive disease. Unsuccessful second-look surgery for patients with a clinical diagnosis of pseudomyxoma peritonei tumor was often related to an inaccurate initial histologic classification of appendiceal mucinous tumor. Also, a transition from less to more aggressive histology was frequently seen in patients dying of this disease. Assessment of tumor histology can predict the outcome if a uniform surgical treatment is used in patients with peritoneal dissemination of mucinous epithelial tumors of the appendix.

Results of treatment of 33 patients with peritoneal mesothelioma.

BACKGROUND: Peritoneal mesothelioma is a rare peritoneal malignancy, representing approximately one-third of all mesotheliomas. It is regarded as a universally fatal cancer with few treatment options. METHODS: Records of 33 patients with peritoneal mesothelioma were reviewed retrospectively. Demographic, clinical and quantitative prognostic indicators were evaluated and analysed statistically using survival as endpoint. Patients were treated by a uniform strategy involving cytoreductive surgery with peritonectomy procedures and perioperative intraperitoneal chemotherapy (cisplatin, doxorubicin). RESULTS: There were ten women and 23 men; mean age was 53.0 years. Asbestos exposure was recorded in five patients and a family history of cancer in 13. Presentation was mainly abdominal distension and pain. Median survival was 31.0 months; overall projected survival at 3 years was 56 per cent. The most significant positive predictive factors of survival were: female sex (P= 0.003), low prior surgical score (P=0.002), completeness of cytoreduction (P=0.0002) and second-look surgery (P=0.019). The morbidity rate for this combined treatment was 33 per cent and the perioperative mortality rate was 3 per cent. CONCLUSION: Although peritoneal mesothelioma is rare, progress in its management has occurred. Survival has been extended and selection factors by which patients may be allocated to aggressive management strategies have been defined.

Early localized peritoneal mesothelioma as an incidental finding at laparoscopy. Report of a case and implications regarding natural history of the disease.

BACKGROUND: Peritoneal mesothelioma is regarded as a fatal disease that presents with progressive ascites in a relatively late stage of its natural history. To the authors' knowledge, prior published articles have not described the early manifestations of this cancer. METHODS: A 30-year-old asymptomatic woman underwent laparoscopy for an infertility workup. Nodules noted in the pelvis were biopsied and determined to be mesothelioma. Standard immunohistochemical studies were performed. Cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy were used for treatment. RESULTS: Multiple (approximately 30) tumor nodules up to 2 mm in dimension and limited to the pelvis were observed and resected. No primary tumor focus was evident. These tumor nodules stained positive for Calretinin and negative for carcinoembryonic antigen immunohistochemically. CONCLUSIONS: In this patient, no incidence for transcoelomic dissemination of mesothelioma from a single primary site was observed. Rather, this patient's clinical presentation suggested that mesothelioma may be multifocal in origin within a limited region of the peritoneal cavity. This hypothesis may support a rationale for aggressive local-regional management of selected patients in whom peritoneal mesothelioma is of limited distribution and mass.

Tall cell variant: an aggressive form of papillary thyroid carcinoma.

Twenty-four cases of the tall cell variant (TCV), a subset of papillary thyroid carcinoma, were identified in a group of 624 patients with thyroid cancer. All pathology specimens were reviewed, and each patient's carcinoma was categorized according to characteristics on presentation, local recurrence, distant metastases, follow-up, and tumor-related mortality. The TCV group was compared with a historical control group (Mazzaferri and Jhiang: 1355 patients). The TCV group had a statistically higher percentage of stage 3 and 4 carcinoma, extrathyroidal invasion, and tumor size less than 1.5 cm than the control group. There was no statistical relationship between age greater than 50 years and stage in the TCV group. No relationship could be found between TCV histology and recurrence or mortality. These findings, combined with those of studies that link stage on presentation to poor outcomes, have led to our conclusion that TCV is an aggressive malignancy warranting appropriate treatment and close follow-up.

The percutaneous needle biopsy is safe and recommended in the diagnosis of musculoskeletal masses.

BACKGROUND: The purpose of this study was to analyze the role of percutaneous core needle biopsy in the diagnosis of musculoskeletal sarcomas. METHODS: One hundred eighty-five biopsy procedures were performed on 161 musculoskeletal tissue masses suspected of being a sarcoma in 155 patients who underwent subsequent tumor resection. A percutaneous core needle biopsy was performed on all masses either in the clinic or under radiologic guidance. If an adequate diagnosis could not be made on the basis of this biopsy specimen, an open incisional biopsy was performed. RESULTS: One hundred seventy-three core needle biopsy procedures were performed: 90 without radiologic guidance, 55 computed tomography guided, and 28 fluoroscopically guided. Twelve open incisional biopsies were performed. Eighty-three sarcomas, 67 benign mesenchymal tumors, and 11 metastatic epithelial tumors were identified. Analysis of the data reveals that only 7.4% of the masses required open biopsy. In 88.2% of the masses, a single percutaneous biopsy procedure was adequate, and no additional biopsy was necessary. There was a 1.1% rate of complications; none caused a change in the patient's treatment plan. There was a 1.1% rate of major diagnostic errors, none of which ultimately impacted on the patient's outcome. There were no unnecessary amputations. Percutaneous needle biopsy showed a positive predictive value of 100%, a negative predictive value of 82%, a sensitivity of 81.8%, and a specificity of 100%. The accuracy of a single-needle biopsy procedure to identify benign versus malignant lesions, exact grade, and exact pathology was 92.4%, 88.6%, and 72.7%, respectively. CONCLUSIONS: The percutaneous needle biopsy was found to be extremely effective and safe for the diagnosis of musculoskeletal masses. This method allowed 88% of patients with suspected sarcomas to undergo a single-needle biopsy procedure before the initiation of definitive treatment. Patients undergoing percutaneous needle biopsy had lower rates of major diagnostic errors and complications than previously described for open biopsy. Open biopsy offered limited additional information when preceded by a needle biopsy, given that these tumors were difficult to identify even after final resection.

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.

Epithelioid sarcoma: an immunohistochemical analysis of 112 classical and variant cases and a discussion of the differential diagnosis.

Epithelioid sarcoma (ES) is a distinctive soft tissue neoplasm with a predilection for the distal extremities of young adults. This tumor typically contains nodular aggregates of epithelioid and spindle cells with zonal necrosis. The neoplastic cells are generally reported to coexpress keratin and vimentin and are often stated to be positive for CD34. However, there is no large series with extensive immunohistochemical data, there are few data with regard to expression of different keratin subtypes, and there are no large series discussing the epithelioid sarcoma subtypes. In the current study, we immunohistochemically evaluated 88 typical and 24 variant (8 angiomatoid, 9 large cell/rhabdoid, and 7 "fibroma-like") ESs. Nearly all ESs with typical histology (94%) were positive for keratin 8 (K8), whereas 72% were positive for K19, 48% for intermediate- and high-molecular-weight keratins (34betaEH12), and 22% for K7; reactivity with the latter two antibodies was usually seen in only a minority of tumor cells. Vimentin reactivity was present in all cases, EMA in 96% of cases and muscle-specific actin and CD34 were noted in 41% and 52% of the cases, respectively. A few ESs (7%) showed focal cytoplasmic CD31 reactivity, but none exhibited a distinctive membrane staining pattern, and examples tested for FVIIIRAg were negative. The angiomatoid, fibroma-like, and large cell-rhabdoid ES variants had immunohistochemical profiles similar to the classic cases, supporting a common pathogenesis. Although not consistently expressed in ES, the presence of CD34 is helpful in distinguishing this entity from primary and metastatic carcinomas and other sarcomas such as malignant rhabdoid tumor.

The role and biology of cryosurgery in the treatment of bone tumors. A review.

The application of liquid nitrogen as a local adjuvant to curettage in the treatment of bone tumors was introduced three decades ago. This technique, termed cryosurgery, was shown to achieve excellent local control in a variety of benign-aggressive and malignant bone tumors. However, early reports showed that cryosurgery was associated with a significant injury to the adjacent rim of bone and soft-tissue, resulting in high rates of fractures and infections. These results reflected an initial failure to appreciate the potentially destructive effects of liquid nitrogen and establish appropriate guidelines for its use. We review the biological effect of cryosurgery on bone, surgical technique, and current indications for its use.

Appendiceal mucocele. Contraindication to laparoscopic appendectomy.

Indications and contraindications to laparoscopic surgery continue to be refined. Laparoscopic appendectomy for acute appendicitis is frequently selected by patients and surgeons, and clinical studies show it to be a reasonable alternative. In this case study, laparoscopic surgery was used to resect an appendiceal mucocele caused by a nonperforated mucinous adenocarcinoma. Implants of mucinous tumor were found widely disseminated on peritoneal surfaces at laparotomy 9 months later. As a result of this case study, the authors suggest that when an appendiceal mucinous tumor is encountered at laparoscopy, a special situation requiring totally atraumatic appendectomy is indicated. This clinical situation should be considered an indication for conversion to open appendectomy. All appendiceal tumors, including the most benign-appearing adenomas, can result in diffuse peritoneal implantation. This is the first report of an appendiceal mucinous tumor resected by laparoscopy associated with subsequent diffuse peritoneal carcinomatosis. This patient presentation reaffirms that dissemination of cancer may be associated with laparoscopic resection of structures containing a malignancy.

Pulmonary metastases in pseudomyxoma peritonei syndrome.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare disease arising from a mucinous cystadenoma of appendiceal origin. The syndrome has been characterized by progressive growth of mucinous tumors, tense mucinous ascites, and ultimately death. Abdominal and pelvic recurrence after resection of intraperitoneal disease occurs in all patients unless adjunctive measures are taken. Local spread of PMP by direct extension to the pleural or pericardial space is uncommon but has been reported in the literature. Here we report development of pulmonary parenchymal metastases after treatment for PMP. METHODS: The charts of 3 patients were retrospectively reviewed for the presentation and management of metastatic PMP. RESULTS: Three patients underwent resection for pulmonary parenchymal metastases of PMP. All patients recovered uneventfully. The continue to do well after 2 to 8 years of follow-up. CONCLUSIONS: Pulmonary metastasectomy for PMP is safe and effective after treatment of intraperitoneal disease.

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.

Primary smooth muscle tumors of the thyroid gland.

BACKGROUND: Primary smooth muscle tumors of the thyroid gland are rare. To date, there are few cases reported of primary thyroid leiomyomas and leiomyosarcomas. METHODS: One leiomyoma and four leiomyosarcomas arising within the thyroid gland were identified in the files of the Endocrine Tumor Registry of the Armed Forces Institute of Pathology. Histologic and immunohistochemical features were reviewed and follow-up obtained. RESULTS: The patients included 2 females, ages 56 and 64 years, and 3 males, ages 45, 68, and 83 years. The patients presented with a mass in the thyroid gland that had increased in size over a number of months. All the tumors originated within a single lobe of the thyroid gland and measured from 1.1 to 9 cm in greatest dimension. Histologically, there was a fascicular pattern of growth comprised of spindle-shaped cells with blunt-ended nuclei. The leiomyoma was encapsulated, cytologically bland, and amitotic; the leiomyosarcomas were invasive with increased cellularity, pleomorphism, a high mitotic rate, necrosis, and hemorrhage. Immunohistochemical staining showed reactivity with vimentin, smooth muscle actin, muscle specific actin, and desmin. The patient with the leiomyoma was alive without evidence of disease 11 years after the initial presentation, with surgical resection as the only treatment. Three of the patients with leiomyosarcomas were dead within 2 years of diagnosis, in spite of aggressive therapeutic intervention. The remaining patient was still alive 10 months after initial presentation with multiple lung metastases. CONCLUSIONS: Smooth muscle tumors of the thyroid gland are distinctive tumors. Leiomyosarcomas can be distinguished from anaplastic carcinoma, although patient outcome is uniformly unfavorable.

Immunohistochemical evidence supporting the appendiceal origin of pseudomyxoma peritonei in women.

Women 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.

Pseudomyxoma peritonei: new concepts in diagnosis, origin, nomenclature, and relationship to mucinous borderline (low malignant potential) tumors of the ovary.

For many years the clinical syndrome of PMP has been enigmatic. Based on recent studies reevaluating the condition, tumors previously designated PMP can now be viewed as two pathologically and prognostically distinct disease processes. Disseminated peritoneal adenomucinosis is characterized by copious mucinous ascites (the classical clinical syndrome of PMP) and histologically bland peritoneal mucinous tumors. The condition can be attributed to a ruptured appendiceal mucinous adenoma in the vast majority of cases. It has an indolent clinical course when surgically treated but may recur over months to years. Peritoneal mucinous carcinomatosis is characterized by abundant peritoneal mucinous tumor, similar to the clinical presentation of adenomucinosis. However, microscopically, the peritoneal tumors have the architectural and cytologic features of carcinoma, are derived from gastrointestinal mucinous adenocarcinomas, and are associated with a significantly worse prognosis than cases of adenomucinosis. A third group of tumors displays intermediate or discordant histologic features but manifests a clinical course very similar to cases of pure peritoneal carcinomatosis. Women often have concomitant ovarian mucinous tumors that suggest primary ovarian neoplasia. Morphologic, immunohistochemical, and molecular studies support the interpretation that the ovarian tumors are secondary and that adenomucinosis is of appendiceal origin in women as well as men. The recognition that the ovarian tumors in nearly all of the cases of DPAM and mucinous carcinomatosis are secondary seriously calls into question the existence of a borderline group of ovarian mucinous tumors. Therefore, primary ovarian mucinous tumors should be classified as either benign or malignant. Tumors exhibiting the features currently interpreted as borderline should be included in the benign group and designated atypical proliferative mucinous tumors.

Parosteal osteosarcoma: value of MR imaging and CT in the prediction of histologic grade.

PURPOSE: To evaluate the use of magnetic resonance (MR) imaging and computed tomography (CT) for predicting the histologic grade of parosteal osteosarcomas. MATERIALS AND METHODS: Sixty parosteal osteosarcomas were analyzed for tumor size and location, presence of a cleavage plane, intramedullary extension, soft-tissue mass (distinct from ossified mass), and the presence and pattern of ossification. Axial and longitudinal views were evaluated for specific osseous sites within the bone. Tumors were classified as low grade (grade 1) or high grade (grades 2-3). RESULTS: There were 32 low-grade lesions and 28 high-grade lesions. Average maximal lengths of low- and high-grade tumors were 7.7 and 15.0 cm, respectively. A cleavage plane was present in 20 (62%) low-grade and 19 (68%) high-grade lesions. On cross-sectional images, intramedullary extension was present in 13 (41%) low-grade and 14 (50%) high-grade lesions. A focal soft-tissue mass distinct from the ossific matrix was identified in 25 (89%) high-grade lesions and in only two (6%) low-grade lesions. All 17 high-grade lesions evaluated with MR imaging were of predominantly high signal intensity on T2-weighted images. CONCLUSION: A poorly defined soft-tissue component distinct from the ossific matrix is the most distinctive feature of high-grade parosteal osteosarcoma and may be an optimal site for biopsy.

Unilateral optic neuritis caused by Histoplasma capsulatum in a patient with the acquired immunodeficiency syndrome.

PURPOSE: To evaluate the potential of Histoplasma capsulatum to cause optic neuritis in the setting of the acquired immunodeficiency syndrome (AIDS). METHODS: We examined a 35-year-old man with a history of AIDS and disseminated histoplasmosis who developed a unilateral progressive optic neuritis of enigmatic origin. An optic nerve sheath biopsy was performed to provide a tissue diagnosis. RESULTS: Histoplasma capsulatum was identified in both the optic nerve sheath and fungal culture. CONCLUSION: Histoplasma capsulatum should be considered in the differential diagnosis of optic neuritis in patients with AIDS, even in the absence of chorioretinal findings.