Prolactin-cell adenoma with signet-ring cells: a case report.

OBJECTIVE: Signet-ring cell changes in the pituitary adenomas are extremely rare. To date, there have been only two reports documenting signet-ring cells in pituitary adenomas, one in a growth-hormone cell adenoma and the other in a nullcell adenoma. This report describes, for the first time, signet-ring cells in a prolactincell adenoma. CASE HISTORY: The patient is a 46-year-old male who presented with severe headache and acute on chronic visual loss. Radiographic studies demonstrated a large cystic pituitary lesion with evidence of pituitary apoplexy. Laboratory values were consistent with a prolactin-cell adenoma. The patient underwent transsphenoidal resection of the prolactin-cell adenoma with significant post-operative improvement. RESULTS: The tumor was composed of sheets of monomorphic round cells with conspicuous nuclei and granular cytoplasm, consistent with pituitary adenoma. Many cells had eccentric, often crescentic-shaped nuclei, imparting a signet-ring appearance and immunostaining was positive for prolactin, denoting an atypical prolactin-cell adenoma. The MIB-1 labeling index was slightly elevated. Electron microscopy demonstrated the presence of vacuolated areas in the cytoplasm that were not membrane bound and did not have specific inclusions. DISCUSSION: This case augments the literature on pituitary adenomas with signet-ring cells. The clinical significance of signet-ring cells in pituitary adenomas is unknown. Accumulation of clinical cases, together with the advances in molecular techniques and experimental models, may yield further insight.

CA-125 and carcinoembryonic antigen assay vs. cytodiagnostic experience in the classification of benign ovarian cysts.

OBJECTIVE: To compare the relative strengths of two factors involved in making an accurate differentiation between functional and epithelial ovarian cysts, along with their combination: (1) the cytologist's level of experience in interpreting ovarian cytology, (2) the use of the tumor markers carcinoembryonic antigen (CEA) and CA-125 in cyst fluid, and (3) a combination of (1) and (2). STUDY DESIGN: Papanicolaou-stained sediments from fluid aspirated from 31 resected ovarian cysts (6 functional and 25 epithelial) were blindly and independently evaluated by five pathologists with varying experience in ovarian cytology. Cyst fluid supernatant was used for CEA, enzyme-linked immunosorbent assay, and CA-125 radioimmunoassay; CEA levels > 5 ng/mL or CA-125 > 5,000 U/mL were considered elevated. Cysts were categorized cytologically and histologically as functional or epithelial and by tumor markers as "neither elevated" or "either or both elevated" (EBE). RESULTS: The agreement of histologic diagnosis with each pathologist's cytologic diagnosis ranged from 53% to 84% (53%, 71%, 83%, 82%, 84%), corresponding to increasing level of experience. The percentage of agreement with EBE was 77%, whereas combined experienced pathologist's diagnosis and EBE was 87%. Kappa equaled .45 for experienced cytopathologist's diagnosis or EBE alone. Kappa equaled .53 when the pathologist or EBE diagnosed an epithelial cyst, indicating results unlikely to occur by chance. CONCLUSION: The distinction of functional from epithelial ovarian cysts is best achieved by combining measurement of the tumor markers CEA and CA-125 with a high level of cytopathology experience.

Diagnostic use of immunohistochemistry in neuropathology.

Immunohistochemistry has revolutionized both the research and diagnostic endeavors of anatomic and surgical pathologists, including neuropathologists. These methods, which use the high specificity of antibody recognition of target antigens, have largely replaced the more capricious, less sensitive, and less specific panoply of metallic impregnations and other histochemical methods that once were characteristics of neuropathology. With immunostaining, specific infectious agents, from ordinary bacteria to spirochetes, fungi, parasites, and especially viruses, can be identified as the causative agents of central nervous system diseases. Understanding of the pathogenesis and establishment of correct diagnoses of neurodegenerative disorders are both improved, and more precise and reliable diagnosis of central nervous system tumors has become a matter of immunophenotypic characterization using panels of relevant antibodies to supplement the recognition of standard histologic patterns. Newer trends in neuropathologic immunohistochemistry point to a better understanding of the molecular pathology of degenerative disorders and of tumors as specifically mutated oncogenetic or neurotoxic antigens are localized and identified in diseased brain and spinal cord tissues.

Primary neuroectodermal tumors of the ovary. A report of 25 cases.

Twenty-five primary ovarian neuroectodermal tumors occurred in females from 6 to 69 (average, 23) years of age; they had the usual presenting symptoms of abdominal swelling or pain. The tumors, which varied from cystic to solid, ranged from 4 to 20 cm (average, 14 cm) in diameter. Microscopic examination revealed three histologic categories--differentiated, primitive, and anaplastic--with the tumors in the first group having a better prognosis than those in the other two groups. Five of the six differentiated gliomas were pure ependymomas, and one was an ependymoma with an astrocytoma component; none contained teratomatous elements. Two patients with stage I tumors were alive 4 and 5 years postoperatively. The one patient with stage IIA tumor was free of disease at 3 years; one of the two patients with a stage III tumor died of tumor after 5 years, and one had two recurrences but was alive and well at 5 years. Twelve tumors were primitive, resembling medulloepithelioma, ependymoblastoma, neuroblastoma or medulloblastoma. Seven tumors had teratomatous foci of other types, including three dermoid cysts. Three patients with stage I tumors were alive at 7 months, 3 years, and 9 years postoperatively; six of seven patients with stage III tumors died of tumor 2 to 20 months postoperatively, and one was alive with disease at 1 year. Seven tumors were anaplastic, resembling glioblastoma. All contained foci of squamous epithelium. One patient with stage IA tumor died of tumor at 2 years, but two were free of tumor after 3 and 4 years. One patient with a stage IIA tumor died of disease after 5 years; another was alive with tumor at 1 year. One patient with a stage III tumor died after 4 months. The differential diagnosis of neuroectodermal tumors of the ovary includes many primary and metastatic ovarian neoplasms of diverse types, and distinction among them is important. Neuroectodermal tumors should be considered when examining unusual ovarian tumors, particularly if the patient is young.

Demyelinating disease versus tumor in surgical neuropathology. Clues to a correct pathological diagnosis.

Clinical presentations as well as radiological and histopathological findings in biopsies from patients with multiple sclerosis (MS) or other demyelinating disorders of the central nervous system are sometimes misleading, resulting in an erroneous diagnosis of brain or spinal cord tumor. We report 17 patients who presented with symptoms mimicking those of brain (14 cases) or spinal cord (three cases) tumors. Computerized tomography or magnetic resonance imaging studies or both were interpreted as consistent with a tumor in each case. All patients underwent surgery, and all 17 pathological specimens were eventually diagnosed as showing demyelinating disease, usually consistent with MS. In each case we examined a variety of histological features and immunohistochemical studies and addressed their relative importance in considering the diagnosis of MS. All cases showed perivascular lymphocytic inflammation with variable amounts of macrophage infiltration, necrosis, and edema. The hypercellularity of the lesions and the presence of atypical reactive astrocytes with mitotic figures were the disturbing features that might have led to the erroneous diagnosis of an astrocytic neoplasm. Immunohistochemistry for astrocytic (glial fibrillary acidic protein) and macrophage (HAM-56) markers are helpful in evaluating biopsies. Our results emphasize the need to perform special stains (i.e., for myelin and axons) that demonstrate myelin loss and relative preservation of axons and allow a correct diagnosis.

Eosinophilic granuloma of the lung presenting as a solitary pulmonary nodule.

A symptomless 58 year old man had an eosinophilic granuloma of the lung that presented as a solitary pulmonary nodule rather than the usual diffuse reticulonodular shadow on the chest radiograph. Only one previous case presenting in this way has been described.

Proliferative myositis in a two-year-old child.

A 2-year-old boy had intermittent pain and mottling of the left thigh. Swelling of the vastus lateralis developed, and a biopsy revealed proliferative myositis. The pathogenesis is unknown, but trauma and ischemia have been implicated. The rarity of proliferative myositis in children, and the possibility of mistaking the lesion for a sarcoma make the case noteworthy.

Plexiform schwannoma.

A 33-year-old man had a multinodular tumor on his left index finger. Microscopy revealed a plexiform nerve sheath tumor resembling schwannoma. Including this case, 11 patients from 9 to 39 years old, have been reported with plexiform schwannoma. One patient had von Recklinghausen's neurofibromatosis, and all but one were free of recurrence from 1.5 to 6 years later. Plexiform schwannoma should be distinguished from plexiform neurofibroma because it appears to have neither a significant association with neurofibromatosis nor a propensity for malignant transformation.

Ependymoma of the ovary: report of three cases.

Three apparently pure ependymomas of the ovary occurred in young women 25 to 35 years of age who presented with abdominal swelling or pain. At operation one tumor was stage IC, and two were stage III. On microscopic examination the tumors contained cells with fibrillary cytoplasmic processes, often arranged around blood vessels to form perivascular pseudorosettes. Immunohistochemical staining for glial fibrillary acidic protein confirmed the nature of the tumor in each case. The patient with the stage IC tumor was alive and well five years postoperatively. One patient with stage III disease died of tumor six years postoperatively, and insufficient time elapsed after treatment of the second to allow meaningful follow-up data. These cases illustrate the rare occurrence of ovarian tumors resembling differentiated tumors of the central nervous system. Recognition and distinction of these tumors from common epithelial tumors, which they may resemble, have important prognostic and therapeutic implications.

Medulloblastoma. The identification of prognostic subgroups and implications for multimodality management.

For 43 medulloblastoma patients who had five-and ten-year actuarial survival rates of 56%, prognostic factors of statistical significance included: T-stage (82% T1,2 versus 46% T3,4; P less than 0.02), M-stage (63% M0,1 versus 0% M2,3; P less than 0.03), and histopathologic tumor score (TS, based upon necrosis, desmoplasia, cytoplasmic processes, and mitoses) (81% TS less than or equal to 5 versus 41% TS greater than or equal to 6; P less than 0.05). Posterior fossa local control rates were also function of T-stage (90% T1,2 versus 38% T3,4) and TS (83% TS less than or equal to 5 versus 38% TS greater than or equal to 6). Combining TS with T-stage, patients fell into three prognostic and local control groups, which may have different future management implications: Small (T1,2) tumors of favorable (TS less than or equal to 5) histology had a 92% ten-year actuarial survival rate with 100% (8/8) local control; no change from current management is suggested. For the intermediate prognosis group (T1,2-TS greater than or equal to 6 or T3,4-TS less than or equal to 5 with 67% and 70% survival, respectively), increasing the irradiation dose alone may improve survival because these tumors exhibited an irradiation dose-response relationship. However, it is the poor prognosis group (T3,4-TS greater than or equal to 6 with 42% survival) which might be suitable for future adjuvant chemotherapy or radiosensitizer trials since there is no evidence that higher irradiation doses improve local control. This article identifies prognostic subgroups based on histologic type and TM staging in medulloblastoma patients which potentially may be utilized to improve therapeutic results, and confirms the value of staging patients with central nervous system malignancies.

Unusual sacrococcygeal embryologic malformations with cutaneous manifestations.

Two unusual sacrococcygeal neuroepithelial heterotopias manifested as masses associated with cutaneous signs. In a 13-month-old infant, a cystic coccygeal medullary vestige was associated with a midline epidermal nevus. In another patient, a lipomeningocele with neuroepithelial heterotopia manifested as a skin tag and mass in the right buttock. In both cases, the malformations probably resulted from abnormal canalization and retrograde differentiation of the distal neural tube. Cystic coccygeal medullary vestige results from dilation of a persistent ependymal cyst present commonly in neonates at the distal part of the coccyx. The lipomeningocele appears to have arisen from an aberrantly formed ependymal canal. The embryologic events that gave rise to the lesions, the differential diagnosis of postrectal masses, and the common association of midline lesions of skin and soft tissue with neural defects are stressed.

Whipple disease of the nervous system.

A 58-year-old man with dizziness and unsteady gait had a 10-year history of behavioral change, impotence, and a progressive peripheral neuropathy. CT revealed low-density, contrast-enhancing lesions in the right pontine tegmentum and the right medial temporal lobe. Temporal lobe biopsy contained a collection of mature histiocytes, with PAS-positive rod-shaped inclusions. These inclusions, when studied by electronmicroscopy, were seen to be membrane-bound bacilliform bodies. Peroral jejunal biopsy contained no such inclusions. Despite treatment with antibiotics, the patient's neurologic illness progressed, and he succumbed to intercurrent sepsis. We believe this to be the first instance in which a lesion of Whipple disease has been identified within the CNS by CT scan, and the diagnosis made antemortem, in the absence of demonstrable systemic disease.

Aspergillosis of the nervous system.

Cerebral aspergillosis currently occurs most frequently with disseminated aspergillosis in immunocompromised hosts. Twelve patients with cerebral aspergillosis in this setting were seen over 10 years. Underlying illnesses were renal transplantation in six cases and one case each of subacute hepatic necrosis, head trauma, glioblastoma, microglioma, and esthesioneuroblastoma. All patients were receiving high dose steroid therapy except one who had ectopic ACTH syndrome. Eleven patients were receiving broad spectrum antibiotics. All patients were febrile and developed progressive pulmonary infiltrates preceding or coincident with neurologic symptoms. Sudden onset of neurologic deficits or seizures occurred in nine of 11 clinically analyzable cases. Brainstem or cerebellar signs and symptoms were a presenting feature in three cases and were eventually seen in five cases. Cranial computerized tomography in four cases showed low absorption areas with minimal enhancement and little mass effect. Neurologic deterioration was rapid with nine of 11 patients dying within 6 days of onset. Neuropathologic examination showed multiple abscess formation in 11 cases and prominent blood vessel invasion in all cases. The sudden onset of stroke-like deficits and brainstem findings in a febrile immunocompromised host with pulmonary infiltrates suggests the diagnosis of cerebral aspergillosis. Two cases of aspergillus meningitis were also seen, one postoperatively.

Malignant meningiomas: CT and histologic criteria, including a new CT sign.

Histologic features that could be correlated with malignancy were assessed by reviewing the microscopic slides of 167 meningiomas. Six tumors had shown two or more recurrences. In three having three or more recurrences, the number of mitoses counted under high power was higher than in those meningiomas showing clinically benign behavior. The radiologic and histologic features of seven meningiomas showing malignant clinical behavior and/or malignant histologic features were also evaluated and correlated. On computed tomography (CT), most of the malignant meningiomas were moderately hyperdense before contrast enhancement, but showed no or minimal calcification. Marked perifocal edema was common. Indistinct tumor margins or, occasionally, deeply extending fringes of tumor interdigitating with brain substance, marked bone destruction, or prominent pannus or tumor, extending well away from the globoid mass, termed "mushrooming," is described for the first time and seems to be the most useful correlate of histologic or clinical malignancy. This sign occurred in five of the seven cases and was absent in about 250 benign meningiomas reviewed. It was visible only at surgery in one additional case.

Medulloblastoma in adults: improved survival with supervoltage radiation therapy.

During the period from January 1962--June 1979, 17 adults (greater than or equal to 16 years of age) received postoperative supervoltage neuraxis radiation therapy for medulloblastoma. An actuarial five- and ten-year survival rate of 46% was achieved, and the major site of recurrence postirradiation was in the posterior fossa. Compared to previous pediatric series, adults may demonstrate more visceral metastases and fare less well after tumor recurrence. Compared to prior series of adult patients, the demonstrated improved survival is attributed to increased doses delivered to the posterior fossa.

Systemic metastases from medulloblastoma: report of two cases and review of the literature.

The clinical and pathologic data from two cases of medulloblastoma with systemic metastases, and 101 previously reported cases were evaluated to define better the clinical presentation and natural history. Patients ranged in age from six months to 48 years, with a mean of 13 years; two thirds of the patients were male. Ventricular shunts had been inserted in 20% of the patients. Systemic metastases occurred on an average of two years after the diagnosis of the primary tumor in patients without shunts, but only 1.3 years in patients with shunts. Fifty-nine percent of the patients were known to have experienced recurrence or spread of medulloblastoma within the central nervous system by the time systemic metastases appeared. Ninety percent showed radiologic evidence of bone metastases, of which 60% were osteoblastic. Bones most frequently involved were pelvis, femur and vertebrae; pain was the most common initial symptom. At autopsy, lymph node metastases were found in 65% and liver metastases were found in 28% of all cases in addition to bone metastases in 82%. Lung metastases occurred in 9% of the patients without shunts, compared with 30% of patients with shunts. The average survival was seven months after the appearance of systemic metastases for patients both with and without shunts. Approximately 5% of patients with medulloblastoma may be expected to develop systemic metastases. This development is associated with increased morbidity and a shortened life expectancy.

Glioma of the uterus. Report of a case with comments on histogenesis.

A 15-year-old girl had a hysterectomy for intractable vaginal bleeding. Examination of the specimen revealed a polypoid tumor that filled the endometrial cavity; microscopical examination disclosed a low-grade fibrillary astrocytoma. Glial tissue in the uterus has been generally considered to arise from implantation of fetal tissue. A reliably negative coital history makes such an explanation unlikely in the present case in which the tissue appeared to be truly neoplastic and of either germ cell or mesodermal origin. The patient is free of disease 6 years later.