Ectopic lacrimal gland of the orbit.

A case of intraorbital ectopic lacrimal gland was evaluated with various radionuclides. CT and MRI with contrast enhancement showed a soft-tissue mass in the orbit. The lesion was gallium-avid, but 18F-FDG PET demonstrated very faint uptake. On early and delayed 201Tl-Cl images, mildly increased uptake and mild retention were observed. Technetium-99m-(V)-DMSA SPECT showed intense accumulation on both the early and delayed images. Technetium-99m-pertechnetate SPECT, demonstrating marked uptake in the lesion, was useful for the differential diagnosis between intraorbital malignancy and this benign lesion. These scintigraphic variations played an important role in the tissue characterization of this uncommon lesion.

Centroblastic and centroblastic-centrocytic lymphomas associated with prominent epithelioid granulomatous response without plasma cell differentiation: a clinicopathologic study of 12 cases.

To clarify the clinicopathologic features of B-cell lymphoma associated with prominent epithelioid granulomatous responses other than immunocytomas, 12 patients were studied. There were six men and six women. The lymphoma generally affected elderly patients (median age, 58.5 years) and was mostly nodal in origin. Seven of the 12 patients had a localized lesion (stage I or II), and five had an advanced lesion (stage III or IV). Histologically, four patients showed a follicular growth pattern and eight a diffuse growth pattern. Based on the updated Kiel classification, nine patients showed centroblastic lymphomas, and three showed centroblastic-centrocytic lymphomas. The epithelioid cells were accumulated in large, poorly demarcated masses. Trabecular fibrosis compartmentalized in the lymph nodes, producing a vague nodular pattern in low-power fields. Immunohistochemical studies of the tumor cells revealed positive membrane staining with L26 in all 12 patients and with LN-1 antibody in 9 of 10 patients. Expression of the bcl-2 protein was present in all seven patients tested. Genotypic investigation exhibited germline configuration of the immunoglobulin heavy chain gene, the T-cell receptor beta-chain gene and the bcl-2 gene in all three patients investigated. By in situ hybridization, Epstein-Barr virus genomes were detected in only a few tumor cells in three of the patients tested. This study indicated that most, if not all, of the B-cell lymphomas with prominent epithelioid granulomatous responses other than immunocytoma were of follicular center cell origin.

Imprint cytology of cat scratch disease. A report of eight cases.

The cytologic features of cat scratch disease (CSD) from eight cases in imprint smears are presented. All patients were clinicopathologically diagnosed with CSD as follows: 1) a history of animal exposure was recorded 2 to 4 weeks before lymphadenopathy; 2) the disease occurred in the autumn and winter months; 3) a characteristic histopathology in the biopsied lymph node specimens was observed; and 4) Warthin-Starry silver stain-positive bacteria were detected in four of the seven cases examined. The characteristic cytologic finding was the presence of confluent epithelioid cells with nearby and central scattering of neutrophils against a background of polymorphic inflammatory cells. Furthermore, a varying number of medium-sized to large lymphoid cells with an appearance suggestive of monocytoid B lymphocytes (MBLs) were noted to be associated with the epithelioid cells. These cytologic findings closely paralleled the histologic patterns of epithelioid cell granulomas, with and without MBLs, which we have previously reported are probably associated with the disease.

Cerebrospinal fluid immunocytochemical analysis and neuroimaging in the diagnosis of primary leptomeningeal melanoma. Case report.

A 20-year-old man presented with slowly progressing symptoms indicative of increased intracranial pressure. Two weeks later he underwent surgery for placement of a ventriculoperitoneal shunt. Cytological examination of the patient's cerebrospinal fluid (CSF) revealed atypical cells that contained no detectable melanin deposits, but proved to be immunocytochemically positive for monoclonal antibodies to melanocytic cells (HMB-45) and S-100 protein. Dermatological and ophthalmological examinations failed to demonstrate any abnormalities. On the basis of these findings, a diagnosis of primary leptomeningeal melanoma was made. Gadolinium-enhanced magnetic resonance (MR) images of the brain and spinal regions obtained 2 months after admission demonstrated typical widespread leptomeningeal enhancement. Results of technetium-99m-hexakis (2-methoxyisobutyl isonitrile) single-photon emission computerized tomography (99mTc-MIBI SPECT) scanning revealed intense uptake of the isotope in the leptomeningeal regions and some cisterns. The patient's condition progressively worsened and he died 5 months after admission. The diagnosis was confirmed at autopsy. Immunocytochemical analysis of CSF performed using HMB-45 and S-100 protein antibodies is important for the diagnosis of leptomeningeal melanoma because of the test's simplicity, high specificity, and sensitivity. Gadolinium-enhanced MR imaging is used to demonstrate the extent of the leptomeningeal melanoma. An additional and supplemental neuroimaging modality, 99mTc-MIBI SPECT scanning has good potential for the detection and diagnosis of leptomeningeal melanoma.

Active immunization of human cancer with tumor cell-associated carbohydrate antigen.

The peanut agglutinin (PNA) receptors isolated from a tumor cell line could elicit antitumor activity by an active immunization. We report here the results of active immunization with a human PNA receptor glycoprotein on the tumor progression of cancer patients. A remarkable regression of cancer and a prolonged life span in patients were obtained after active immunization with a tumor cell-associated carbohydrate antigen.

Placental metastasis from maternal primitive neuroectodermal tumor.

The occurrence of placental metastasis from maternal primitive neuroectodermal tumor (PNET) is extremely rare. A 33-year-old woman at 33 weeks' gestation was admitted to the hospital. She died of the disease on hospital day 28 because the unresectable tumor was located over a wide area of the retroperitoneum. A neonate was delivered by a caesarean section without evidence of disease and has survived to 1 year of age. Pathologically, the tumor consisted of monotonous small round cells with a high nuclear cytoplasmic ratio, including several pseudorosettes and Homer-Wright-type rosettes. On immunohistochemical examination, the tumor cells were positively stained for neuron-specific enolase. Microscopically, the placenta showed intervillous metastasis from the maternal PNET. This case may be the first one of placental metastasis from PNET ever reported in the literature.

Suppurative lesions without prominent epithelioid cell response in abscess-forming granulomatous lymphadenitis.

To clarify the clinicopathological significance of the suppurative lesions without an epithelioid granulomatous response (SLs without Ep) in lymph nodes and their relationship to abscess-forming granulomatous lymphadenitis (AGL) and cat scratch disease (CSD), 10 cases were assessed clinicopathologically and immunohistologically. SLs without Ep were located in the subcapsular sinus, paracortical area and medullary cords, but not in the germinal centers. The microabscesses were surrounded by collections of monocytoid B-lymphocytes (MBLs), histiocytes without epithelioid features, neutrophils, small lymphocytes and small numbers of plasma cells. The majority of the MBLs seen in the SLs without Ep were of the large cell type. The histological triad of toxoplasmic lymphadenitis, i.e., reactive follicular hyperplasia, small clusters of epithelioid cells and aggregates of MBLs, were also seen in all cases. Some of the clinical and pathological findings in our 10 cases were characteristic of CSD, i.e., (1) cat exposure before the lymphadenopathy was in four of the 10 cases, (2) occurrence in autumn and winter months in all cases, (3) typical suppurative granulomas surrounded by palisaded epithelioid cells were in four of the 10 cases, and (4) Warthin-Starry silver stain-positive bacteria were detected in seven of the 10 cases. The results of our study suggest that SLs without Ep are an early stage of CSD.

Imprint cytology of large B-cell lymphoma with high content of epithelioid cells. A report of two cases.

An association of epithelioid cell reaction in follicular center cell lymphomas seems to be a rare phenomenon. The cytological features of this type of B-cell lymphoma from two patients are presented. In both cases, immunohistochemistry applied to paraffin sections revealed reactivity of tumor cells for CD10, 20 and 79a. The first patient, a 77-year-old male, presented with bilateral inguinal bulky masses. The second patient, a 76-year-old female, revealed left supraclavicular bulky masses. Imprint cytological specimens of these two cases showed large lymphoid cells interspersed with epithelioid histiocytes, which were present in small aggregated clusters or in isolated forms. Most tumor cells showed centroblastic morphology, whereas the minority of them looked like immunoblasts. Occasionally, a monotonous proliferation of these large atypical blastic cells was also detected. On the other hand, in some parts of the imprint specimens, numerous epithelioid cells obscured the underlining tumor cells. Reactive cells other than epithelioid cells were not prominent. These cytologic features closely resembled the histologic patterns of this rare follicular center cell lymphoma. Careful examination of the cytological specimens is needed to detect the monotonous proliferation of tumor cells to establish the diagnosis of malignant lymphoma.

Florid reactive follicular hyperplasia in elderly patients. A clinicopathological study of 23 cases.

Florid reactive follicular hyperplasia (FRFH) of the enlarged lymph node in elderly patients requiring biopsy is a relatively uncommon phenomenon as compared with younger age groups. We experienced 23 patients, aged 60 years or more, from whom the biopsied lymph node specimens histologically showed inappropriate FRFH for their age, in the period between 1982 and 1996. These cases were morphologically subdivided into three groups, FRFH with interfollicular plasmacytosis, that with progressive transformation of germinal center, and FRFH without additional specific findings. FRFH with interfollicular plasmacytosis were observed in 11 cases, all of whom were accompanied with several immunological abnormalities (six with rheumatoid arthritis, three with multicentric Castleman's disease and one each with myoepithelial sialoadenitis and autoimmune hemolytic anemia). Three men with uncertain etiology exhibited an unusual histology of progressive transformed germinal centers which were clinically characterized by a bulky neck mass. Among the nine cases with nonspecific FRFH, only four had a specific etiology (one each with adult onset Still's disease, chronic sinusitis, Epstein-Barr virus infection and infectious lateral cervical cyst), while the other five with unknown etiology showed abnormal laboratory findings suggestive of an abnormal humoral immune response, i.e. hypergammaglobulinemia and seropositivities for some autoantibodies. None of our patients developed malignant lymphoma during the follow-up period. Of note, 16 (70%) of the 23 cases were found to be associated with various types of imbalances of the immune system, some of which appeared to be currently ill-defined as clinicopathological entities that were simply categorized as autoimmune disease.

Occurrence of monocytoid B-cells in reactive lymph node lesions.

Benign monocytoid B-cells are a peculiar subset of B-cells. They are closely related to marginal zone B-lymphocytes, show cytological diversity and may be recognized in a variety of reactive lymph node conditions. To analyze the incidence, cytological spectrum and phenotypic features of benign monocytoid B-cells, we investigated a series of 301 consecutively biopsied and unselected cases of reactive lymph node change from 1988 and 1995. A monocytoid B-cell reaction was identified in 46 (15%) cases and could be cytologically subclassified into two groups: 31 (67%) cases with common-type cells and 15 (33%) cases with large, transformed cells, according to the description by Plank et al. [19]. These reactions were regularly associated with follicular hyperplasia (95%) and were part of an epithelioid cell response in 24 cases (50%). Immunohistologically, both types of benign monocytoid B-cells were negative for bcl-2 protein expression, which was in contrast to the bcl-2 positive reaction in marginal zone B-lymphocytes and their neoplastic counterpart in monocytoid B-cell lymphoma. An association of Epstein-Barr virus (EBV) with monocytoid B-cells was investigated by in situ-hybridization. EBV genomes were detected in five (15%) of 31 cases tested. In each of these five cases, positive cells were represented in both high and low numbers. The morphologic features of the EBV-positive cells were not consistent with monocytoid B-cells, but rather with medium-sized to large lymphoid cells. It appeared that the occurrence of monocytoid B-cell reaction in reactive lymph node lesions was not related to EBV infection in the majority of cases.

Systemic lupus erythematosus (SLE) lymphadenopathy presenting with histopathologic features of Castleman' disease: a clinicopathologic study of five cases.

Lymph node enlargement is common in active systemic lupus erythematosus (SLE), a disease characterized by well defined clinical criteria. Although numerous reports have described the characteristic histology of SLE lymphadenopathy to include necrotizing lesions and hematoxylin bodies, no detailed description has examined the histopathologic features that are similar to Castleman's disease (CD) in SLE patients. In this report, we describe the clinicopathologic findings of CD-like peripheral lymphadenopathy, which was identified in five (26%) of 19 SLE patients. These five patients were all female with an age range of 24 to 44 years, and four of them presented with multicentric lymphadenopathy. They also had systemic symptoms and abnormal laboratory findings, indicating active disease, although two patients had not fulfilled the diagnostic criteria of SLE at the initial disease. The size of the enlarged lymph nodes seldom exceeded 2.0 cm in diameter, and biopsies revealed histopathologic features similar to CD, of intermediate type in three patients and hyaline vascular type in two according to the classification of Flendrig [7]. Immunohistochemical studies demonstrated polyclonal plasma cell populations in all five cases. Epstein-Barr virus genomes were detected in the small lymphocytes of two of the three cases examined by in situ hybridization studies. Recently, the histopathologic findings of CD have been associated with a disrupted immune response, and the present data suggest that SLE should be listed as one of the diseases showing the histopathologic features similar to CD.

Benign clear cell tumor of the lung in an 8-year-old girl.

A case of "benign clear cell tumor of the lung" occurred in an 8-year-old girl. The tumor was a solid well-circumscribed mass, measuring 1 cm in diameter. Histologically, it consisted of polygonal cells intermingled with large, thin-walled vessels. Glycogen was scarce in paraffin sections; however, electron microscopic observation revealed a large amount of glycogen. Intracytoplasmic filaments were not observed, but scattered pinocytotic vesicles and plaquelike densities along the plasma membrane were found.

A selective pulmonary thrombosis associated with sepsis-induced disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a pathologic condition associated with critical illnesses, including sepsis. Recent studies have suggested that endogenous cytokines and leukocytes are involved in major roles of its pathophysiology. We report a case of sepsis-induced DIC due to pneumonia that was associated with diffuse and selective thrombosis in pulmonary arteries, yielding to sudden death from pulmonary massive embolism. This report suggests that the selective and lethal pulmonary thromboembolism progresses under the standard therapies in sepsis-induced DIC.

Necrotizing granulomatous vasculitis of transverse colon and gallbladder.

A 52-year-old man suffering neither from allergies or asthma, with necrotizing granulomatous vasculitis (allergic granulomatosis) of the transverse colon and gallbladder is presented. During an emergency laparotomy, segmental necrosis of the mesenteric side of the mid-transverse colon, and a bulky enlarged gallbladder were found. The affected colon was resected and cholecystectomy was performed. Histological findings included necrotizing granulomatous vasculitis of the small- and medium-sized muscular arteries and adjacent veins with tissue infiltration by eosinophils and extravascular eosinophilic granulomas. These histological features were compatible with allergic granulomatous angitis described by Churg and Strauss (CSS). The patient had neither asthma nor involvement of two or more extra-pulmonary organs which is a key clinical criteria of CSS and fulfilled the criteria of eosinophilia alone. Although pulmonary vasculitis was not confirmed in this patient, the histological diagnosis of this patient was definitive CSS. Localised PAN with allergic granulomatosis or an isolated or limited form of CSS based on these clinical features may be an alternative entity.

[The ultrastructural study on the relationship between Chlamydia trachomatis and the host cell in adhesion and during and after invasion].

Chlamydia trachomatis (C. trachomatis) is 0.4-0.5 microns in diameter in the EB stage, with the nucleoid located eccentrically within it. We studied the relationship between the eccentric nucleoid and the host cell surface under electron microscope, when C. trachomatis was in adhesion to the host cell and during and after invasion into the host cell. When C. trachomatis adheres to and invades a host cell, the eccentric nucleoid is located on the side distant from the host cell surface (44 of 66, 66%). The 1 x 3 chi-square test indicates that the difference is significant at p less than 0.001. After C. trachomatis invades a host cell, the eccentric nucleoid is located on the side close to the host cell surface (61 of 138, 44%). The 1 x 3 chi-square test shows the difference to be significant at p less than 0.001. However, since the latter (44%) is less than the former (66%). C. trachomatis revolves between adhesion and the completion of the invasion. The 2 x 3 chi-square test shows a significant difference at p less than 0.001.

[A case of neoplastic angioendotheliosis--serial study of magnetic resonance imaging].

The case of a 59-year-old man who was diagnosed as having neoplastic angioendotheliosis by biopsy of a small hemangioma on the skin is reported. The clinical features were characterized by hypersomnia, memory disturbance, disorientation to time and mild left hemiplegia including the face. Laboratory findings showed an elevated erythrocyte sedimentation rate, increased serum LDH, increased CSF protein and pleocytosis in the CSF. The CSF level of IgG was also elevated and was associated with the appearance of oligoclonal IgG bands. The biopsy specimen of the hemangioma on the skin revealed that some small vessels were packed with atypical mononuclear cells which were positive for anti-B cell antibody. Magnetic resonance imaging (MRI) of the brain detected multiple lesions located in the cerebellum, thalamus and caudate nucleus. The left paramedian thalamic lesion might be responsible for his characteristic mood and behavioral changes. The serial MRI study disclosed that some lesions progressively enlarged and duplicated in number. These findings might be typical for neoplastic angioendotheliosis, in which the rapidly proliferating cells occluded small vessels one after another in the central nervous system. The serial study of MRI may serve an important diagnostic purpose in this disease, although most patients with this disease, so far, have been diagnosed by autopsy.

[A case of remarkable regression of lung adenocarcinoma with PSK immunotherapy].

An asymptomatic 84-year-old man was admitted to our hospital for a further examination of an abnormal shadow in the right lower lung (S9) on chest X-ray film. Sputum and specimens of transbronchial brushing showed cytological characteristics of well differentiated adenocarcinoma. Considering his age, his family did not agree to any surgical operation, irradiation or intensive chemotherapy. Therefore, using PSK: 3.0 g/day, immunotherapy was started on October 26, 1984. However, the abnormal density continued to increase in size and was observed radiographically to infiltrate to the neighboring segment (S6) over the following four months. From March 1985, the tumor regressed gradually and had almost disappeared on chest X-ray films by December 1985. Since then, this remission has been maintained by administration of PSK alone (3.0 g/day).