Clinical significance of MUC1, MUC2 and CK17 expression patterns for diagnosis of pancreatobiliary arcinoma.

Pancreatic cancer is characterized by aggressive growth and resistance to treatment. Identification of unique biomarkers for diagnosis and prognosis is important for treatment of this disease. We investigated the expression patterns of mucin 1 (MUC1), mucin 2 (MUC2) and cytokeratin 17 (CK17) in both normal tissues and metastatic adenocarcinomas using immunohistochemistry (IHC). We have shown that MUC1 (pan-epithelial membrane mucin), MUC2 (intestinal-type secretory mucin) and CK17 can be used as a panel of markers to distinguish collectively pancreatobiliary carcinoma from other primary site carcinomas. Tumors originating in the pancreatobiliary system showed an expression pattern of MUC1 (+), MUC2 (-) and CK17 (+). By contrast, tumors arising from the colorectal region were MUC1 (-), MUC2 (+) and CK17 (-), while tumors originating from non-pancreatobiliary system tissue expressed a MUC1 (+), MUC2 (-) and CK17 (-) profile. More importantly, the MUC1 (+), MUC2 (-) and CK17 (+) result showed greater sensitivity than CA19-9 by IHC, which is the currently accepted and widely used pancreatic tumor marker for diagnosing pancreatic cancer. Thirteen of 51 cases (25%) of pancreatobiliary adenocarcinomas with the pattern MUC1 (+), MUC2 (-) and CK17 (+) showed no immunoreactivity for CA19-9, while 34/51 (67%) cases having MUC1 (+), MUC2 (-) and CK17 (+) were correlated with positive CA19-9 staining. Our data support using an antibody panel of MUC1, MUC2 and CK17 to enhance current methods for pancreatic cancer diagnosis by identifying specifically the primary tissue of origin.

Synovial sarcoma of the suboccipital region of the neck.

A synovial sarcoma (SS) is an uncommon malignant soft-tissue tumor, which in spite of its name does not arise from synovial tissue. It is so named because of its histologic similarity to synovium. An SS originates from mesenchyme, not from synoviocytes and usually manifests as a biphasic tumor with both malignant-epithelial and spindle-cell components. Monophasic epithelial and spindle-cell presentations may cause a diagnostic dilemma. Diagnosis should include immunocytochemistry using cytokeratin and/or epithelial membrane antigen; vimentin further helps to eliminate any histologic confusion. These tumors are most commonly found in the extremities. When located near a joint, invasion occurs only by secondary extension. Rarely are SSs found in the neck, especially in the posterior aspect, as reported here.

Urothelial injury from ethylenediaminetetraacetic acid used as an irrigant in the urinary tract.

Although solutions containing disodium ethylenediaminetetraacetic acid (EDTA) will dissolve calcium oxalate stones in vitro, the safety of such solutions as urinary tract irrigants is questionable. These studies were designed to assess the degree of urothelial damage produced by the mildest EDTA formulation which has been reported to be effective. Rabbit bladders were irrigated antegrade via a ureterotomy for 20 hours and then removed for histological examination. A 0.03 M solution of disodium EDTA at pH 7.5 produced considerably more urothelial injury than did an otherwise identical solution of calcium EDTA (p = 0.006). The bladders from the latter group were undistinguishable from those irrigated with saline. As prior saturation of EDTA with calcium completely eliminated the tissue injury, these studies indicate that the same calcium chelating property which makes this chemical effective also makes it toxic. There was enough tissue damage from the relatively mild formulation used to suggest no EDTA solution yet formulated is safe for clinical use.

Rheumatoid nodule of the temporal bone.

A 69-year-old woman with severe rheumatoid arthritis presented with a history of chronic otitis and a facial nerve paralysis. She was found to have a rheumatoid nodule involving the mastoid and mesotympanum. This is believed to be the first reported case of a rheumatoid nodule involving the temporal bone.

Progressive multifocal leukoencephalopathy: a burnt-out case.

A patient with Hodgkin's disease developed progressive multifocal leukoencephalopathy (PML), documented by brain biopsy to be associated with JC virus infection. His disease progressed over several months, resulting in severe neurological deficit, but then stabilized with little or no further clinical progression during the remaining year of his life. Histopathological evaluation of the brain at autopsy supported the clinical impression that brain infection was arrested. Whereas the brain biopsy exhibited the histological features of active PML including giant bizarre astrocytes, at postmortem examination brain lesions appeared inactive, with regression of astrocytic changes and elimination of oligodendroglial inclusions. Similarly, JC virus antigen, present in the brain biopsy, was not detected in the autopsied brain. This case provides further evidence that PML is not invariably fatal and that clinical and cytological remission can occur.

Neuroblastoma, tuberous sclerosis, and subependymal giant cell astrocytoma.

A patient with Stage III paratesticular neuroblastoma diagnosed in infancy was treated with radiotherapy and chemotherapy. Typical depigmented "ash leaf" skin lesions of tuberous sclerosis appeared during early childhood. At 7 years of age he underwent craniotomy for a subependymal giant cell astrocytoma. The occurrence of neuroblastoma, tuberous sclerosis, and astrocytoma is unique, and supports the suggested relationship between neural crest tumors and hamartoma syndromes.

Xenograft of human malignant glial tumors into brains of nude mice. A histopatholgical study.

Sixteen of 21 human malignant glial tumors were successfully heterotransplanted into the brains of nude mice, and one other was transplanted into the brain after prior subcutaneous heterotransplantation. Most xenografts grew preferentially as diffusely infiltrating tumors within hemispheric white matter, generally sparing cortex and deep gray matter. The heterogeneity of most in vivo human tumors gave way to a tumor of generally uniform cell type while growing in nude mice. From six human tumors, all glioblastomas, there emerged histologic patterns or cell forms that were not evident in the original tumor. Tumors from 15 patients were treated with standard chemotherapeutic agents while growing in nude mouse brains. The most common morphologic change induced in tumors by several agents was a distinctive giant cell change characterized by large bizarre nuclei and abundant cytoplasm. It is concluded that the human brain-tumor-nude-mouse xenograft model offers morphological parallels with the clinical situation, but selects for growth only some of the many subpopulations of the human tumor. Such selection imposes restriction on the clinical inferences that may be drawn from this model.

Multifocal varicella-zoster virus leukoencephalitis temporally remote from herpes zoster.

Two patients with cancer, one with Hodgkin's disease and the other with a granulosa cell tumor of the ovary, developed a progressive, eventually fatal infection of the central nervous system exhibiting multifocal symptoms and signs. Pathologically, gross abnormalities of the brain resembled those in progressive multifocal leukoencephalopathy (PML), with discrete and confluent plaque-like lesions concentrated in the white matter, particularly along the gray-white junction. Microscopically, pathological changes differed distinctly from those associated with PML; in addition to confluent foci of white matter injury characterized by early demyelination and subsequent necrosis, prominent Cowdry type A eosinophilic intranuclear inclusions were noted in oligodendrocytes, astrocytes, and neurons. By electron microscopy, intranuclear spherical particles consistent in size and appearance with herpesvirus nucleocapsids were found within the lesions. Immunoperoxidase studies detected varicella-zoster virus (VZV) antigens in infected cells, implicating this virus as the responsible agent despite a lapse of many months between the cutaneous herpes zoster and onset of cerebral symptoms in both patients.

Supratentorial recurrences in medulloblastoma.

Four children with medulloblastoma had massive supratentorial recurrences in the region of the cribriform plate after adequate craniospinal irradiation. The pathogenesis of these recurrences is probably related to underdosage to this region by shielding of the eyes. This hypothesis was corroborated by autopsy findings in two other patients in whom subfrontal implants were histologically different from recurrences elsewhere. Two possible solutions to avoid this problem in the future are suggested.

Meningeal gliomatosis: a review of 12 cases.

Diffuse or multifocal invasion of the leptomeninges by malignant glioma (meningeal gliomatosis) is believed to be rare. From 1971 through 1977, 11 of 52 patients with intracranial malignant gliomas examined at autopsy were found to have meningeal gliomatosis, and 1 additional patient was diagnosed clinically without autopsy (12 cases total). Eight of the 12 patients were diagnosed antemortem with positive cerebrospinal fluid (CSF) cytology, while the other 4 patients were diagnosed at autopsy only. All 11 autopsied patients had multifocal or diffuse meningeal tumor distant from the primary site; 8 patients had spinal subarachnoid seeding with tumor encroachment of cauda equina and spinal nerve roots, and 9 patients had tumor invasion into the lateral ventricles. Three patients had symptomatic spinal cord compression at the thoracic or lumbar level, and 10 patients had hydrocephalus. These 12 patients with meningeal gliomatosis were compared with the other 41 autopsied malignant glioma patients without the complication (controls); the patients with meningeal gliomatosis were significantly younger (mean age, 40 versus 57 years; p less than 0.005). Patients with meningeal gliomatosis lived somewhat longer (median, 49 weeks) compared to controls (35 weeks), but the difference was not statistically significant. With the advance of chemotherapy, patients with malignant glioma are living longer and the incidence of meningeal gliomatosis may rise. The diagnosis of meningeal gliomatosis can be suspected, especially if hydrocephalus is present, and can often be confirmed by CSF cytology.

Progressive white matter destruction following irradiation of an extracranial neoplasm.

Although numerous "cures# have been reported following surgical extirpation of symptomatic foci of cerebral radiation nerosis, delayed progressive white matter destruction and neurological deterioration may occur in some patients who survive for prolonged periods after operation. The postoperative appearance on CT scans of hypodensity within heavily irradiated white matter structures at a distance from the initial radionecrotic focus or operative site suggests continuing radiation-induced tissue injury and a poor prognosis. Anticipated survival as well as administered radiation dose must be taken into account when "safe# radiation thresholds are calculated.

Leukoencephalopathy following high-dose iv methotrexate chemotherapy with leucovorin rescue.

Seven patients with bone or soft tissue sarcomas but without metastatic CNS disease developed a chronic leukoencephalopathy after high-dose (8000-15,000 mg/m2) iv methotrexate (MTX) chemotherapy with leucovorin (LV) rescue. Approximately 12 MTX-LV treatments were administered over a 3-7 month period. None of the patients had cranial irradiation. The syndrome usually began several months after the initiation of chemotherapy with subtle personality changes followed by a progressive dementia, focal seizures, pseudobulbar palsy, spastic quadriparesis, and stupor. Computerized tomographic scans revealed diffuse white matter hypodensity in five patients and atropic changes in five patients. Serum MTX concentrations were elevated in four of six patients prior to several MTX-LV treatments, suggesting that MTX persisted in tissues for a long time. Abnormally high levels of MTX were detected in the cerebrospinal fluid of all four patients several days after an MTX-LV treatment, at a time when their encephalopathy was most severe. Pathologic brain material was obtained from three patients and revealed a spectrum of abnormalities. The syndrome observed in our patients clinically resembles the one described in children with acute lymphatic leukemia who received cranial irradiation and large cumulative amounts of low-dose (12-20 mg/m2) systemic MTX without LV.

Meningiomas with conspicuous plasma cell-lymphocytic components: a report of five cases.

Five meningeal neoplasms grossly resembling meningiomas but histologically containing meningothelial cells together with abundant plasma cells and lymphocytes are reported. These masses are regarded as meningiomas with extensive plasma cell--lymphocytic infiltrates.