An autopsy case of renal cell carcinoma associated with extensive peliosis hepatis.

An autopsy case of renal cell carcinoma with extensive peliosis hepatis is reported. The patient was a 34-year-old female, who had had a left nephrectomy for renal cell carcinoma but died of multiple metastases one year and 4 months after surgery, despite chemotherapy and interferon treatment. At autopsy, the liver was enlarged markedly with multiple metastatic nodules and the non-neoplastic hepatic parenchyma had a spongy appearance, due to diffusely scattered, blood-filled cystic lesions. Histological examination showed the oval to irregular shaped blood-filled spaces were lined by hepatic cell cords and located mainly in the periportal area. In addition, almost all of the sinusoids were dilated and communicated with the cystic blood-filled spaces, which also communicated directly with branches of the portal veins at various levels. Several interlobular portal branches were obstructed. The causative mechanism of peliosis hepatis has yet to be elucidated, although some causative conditions have been proposed. In this case, renal cell carcinoma may have caused the sinusoidal dilatation and the vascular changes in the portal areas, such as obstruction of terminal portal branches, may have contributed to its formation.     

Giant cell tumor of the lung: An autopsy case report with immunohistochemical observations

Tumors resembling giant cell tumor (GCT) of bone are well known to occur in other organs and many cases have been reported to date. While GCT occurring as primary lesions in the lung are extremely rare, the authors experienced such a tumor at an autopsy of a 77 year old woman and subsequently performed histological and immunohistochemical examinations. The clinical and morphologic characteristics of this case are documented, and the literature concerning this type of tumor is reviewed. The present tumor of the lung was histologically characterized by proliferation of benign-looking osteoclast-like giant cells in association with slightly atypical mononuclear cells. The tumor cells were immunohistochemically positive for histlocytic markers but negative for epithelial markers. This case appears to be the first reported benign giant cell tumor of the lung in which histiocytic differentiation of mononuclear cells was suggested by immunohistochemistry.     

An autopsy case of malignant histiocytosis with Reed-Sternberg-like cells

We report an autopsy case of malignant histiocytosis. The clinical course was rapidly progressive and terminated with jaundice and respiratory failure. Histologically, there was diffuse infiltration of large atypical cells in the liver, spleen, lymph nodes and bone marrow. It was of interest that these tumor cells contained a number of bizarre multinucleated cells histologically indistinguishable from Reed-Sternberg cells of Hodgkin's disease, and that these atypical cells expressed DAKO M1 (identical to Leu M1) and Ki-1 antigens and also showed binding to peanut agglutinin (PNA), representative markers of Reed-Sternberg cell. An absence of epithelial membrane antigen and presence of Leu M1 antigen in the tumor cells made a diagnosis of Ki-1 lymphoma unlikely. This case study showed that giant or pleomorphic cells indistinguishable histologically and phenotypically from Reed-Sternberg cells occur in malignant histiocytosis.     

An autopsy case of extraskeletal Ewing's sarcoma followed up for 24 years

A long-term (24 years) follow-up case of extraskeletal Ewing's sarcoma is reported. The light microscopic examination showed features hardly indistinguishable from Ewing's sarcoma of the bone, that is, the tumor cells were diffusely arranged and uniform in size and shape, and possessed glycogen in the cytoplasm. Homer-Wright rosettes were found only in the autopsy material. An immunohistochemical study using a neural marker (neuron-specific enolase) demonstrated positive staining in most tumor cells. An ultrastruc-tural study revealed intracytoplasmic glycogen particles and incomplete neural characters as follows: the cytoplasmic processes resembled neural processes without neurosecretory granules, microtubules or neurofilaments. These findings suggest that this case finally acquired an incomplete neural character with repeated recurrence. This tumor was diagnosed extraskeletal Ewing's sarcoma, but in future it may be categorized as primitive neuroectodermal tumor (PNET).     

An autopsy case study of lymphocytic hypophysitis induced by nivolumab treatment for esophageal malignant melanoma

Immune checkpoint inhibitors such as anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed death-1 antibodies are effective against malignant tumors. However, they induce unique adverse events known as immune-related adverse events. Hypophysitis is one of the most frequent immune-related adverse events of anti-cytotoxic T-lymphocyte antigen-4 therapies. However, there have been few reports describing the pathological findings of hypophysitis induced by anti-programmed death-1 antibodies. The present case is the first autopsy case of hypophysitis induced by nivolumab monotherapy, an anti-programmed death-1 antibody. Pathologically, lymphocytes infiltrated the anterior lobe of the pituitary gland, and the number of pituitary cells, especially adrenocorticotropic hormone-positive cells, decreased. However, necrosis and remarkable fibrosis were not observed. Immunohistologically, some pituitary cells expressed programmed death-ligand 1. Lymphocytes were predominantly CD8-positive T cells, and CD68-positive macrophages and CD20-positive B-cells were also observed. IgG and C4d were deposited on pituitary cells, but IgG4 (a subclass of nivolumab) was not detected. These findings indicate that type IVc and type II hypersensitivity mechanisms may occur in hypophysitis induced by anti-programmed death-1 antibodies and that the inflammatory mechanisms underlying hypophysitis induced by anti-programmed death-1 and anti-cytotoxic T-lymphocyte antigen-4 antibodies are different.     

Dedifferentiated chondrosarcoma of the rib with a malignant mesenchymomatous component: An autopsy case report

A rare variant of dedifferentiated chondrosarcoma wlth malignant mesenchymomatous component in a 57-year-old male is reported. The patient presented with a posterior mediastinal mass arising from the left eighth and ninth ribs showing well differentiated, low-grade chondrosarcoma. Five years later, local recurrence occurred and an excised specimen also showed the same histological features as the primary tumor. Another 6 years later, the tumor recurred and metastasized to the multiple organs, the patient dying 4 months later. Autopsy revealed that the recurrent and metastatic tumors showed malignant mesenchymomatous 'dedifferentiation' of chondrosarcoma composed of rhab domyosarcoma, angiosarcoma, chondrosarcoma, osteosarcoma, and leiomyosarcoma, in addition to fibrosarcomatous areas. Although the less differentiated component of dedifferentiated chondrosarcoma usually shows the histological features of malignant fibrous histiocytoma and fibrosarcoma, multilineage differentiation can occur in that component. The phenomenon of 'dedifferentiation' in chondrosarcoma and the relationship to and distinction from malignant mesenchymoma of soft tissue and bone are discussed.     

Cleaved and multilobated cell immunocytoma of low grade malignancy with amyloid. An immunohistochemical and electron microscopical study

An unusual variant of immunocytoma of low grade malignancy, cytologically resembling follicular cleaved-cell malignant lymphoma is described. Presence of heavy deposits of amyloid, intracytoplasmic monoclonal IgM-kappa immunoglobulin, cells with Dutcher inclusions, electron-microscopic features and negativity of T-cell markers led to diagnosis of immunocytoma. After cytostatic chemotherapy the lymphoma changed its morphology into typical lymphoplasmacytoid immunocytoma.     

Functional evidence for the recognition of endogenous peptides by autoreactive T cell clones

The fine specificity of two human T cell clones responding to autologous HLA-DR1 expressing antigen-presenting cells (APC) in the absence of nominal antigen has been investigated using Epstein-Barr virus-transformed B cells (BCL) of known DR beta 1 domain sequence. It was found that responsiveness was markedly affected by changes in a limited number of residues in this domain. Substitution of the DR1 beta sequence at one residue, position 74, even conservatively, was found to be particularly significant. Located on the beta 1 domain alpha-helix, this residue is predicted to point into the antigen-binding groove and is therefore unlikely to make contact with the T cell receptor. This finding suggests that these T cells are specific for a bound endogenous peptide within the autologous major histocompatibility (MHC) binding groove. The autospecific T cell clones also responded to murine L cell transfectants expressing DR alpha DR1 beta as well as to transfectants expressing the mouse/human hybrid MHC molecule I-E alpha DR1 beta but not to the reciprocal combination DR alpha I-E beta, thus confirming the importance of the beta 1 domain to T cell recognition. In contrast to the autocytotoxicity observed with BCL, cytolysis of the murine L cells expressing the HLA-DR1 molecule was slight and only found at high effector-target ratios. In addition, although fixation enhanced the recognition of BCL, capacity of the murine L cells bearing the HLA-DR1 molecule to stimulate T cell clone proliferation was markedly reduced by aldehyde fixation. When taken together, these results suggest that the endogenous peptides recognized by these autoreactive T cells are of human origin.     

An autopsy case of diffuse myelomatosis associated with systemic kappa light chain deposition disease (LCDD). A patho-anatomical, immunohistochemical and immunobiochemical study

A case of systemic light chain deposition disease in a 48-year-old man is presented. Clinically, the patient showed the signs of multiple organ (liver, heart and kidney) failure, but multiple myeloma was not diagnosed. Autopsy revealed generalized deposition of hyaline, a Congo red-negative substance, especially in the arterial walls of various organs. In the bone marrow, myelomatous proliferations of plasma cells positive for kappa light chain were recognized. The deposited substance was ultrastructurally different from amyloid fibrils, and was identified as kappa light chain by immunohistochemistry. A liver tissue extract was immunobiochemically examined and the deposited substance was confirmed to consist of kappa light chain, its molecular weight being approximately 14,000 to 17,000 Da.     

An autopsy case of intestinal Behcet's disease with sacroiliitis accompanied by myelodysplastic syndrome with trisomy 8. ]

Here we described an autopsy case of intestinal Behcet's disease with sacroiliitis associated with myelodysplastic syndrome (RAEB-t, 8+). Over twenty cases of Behcet's disease associated with myelodysplastic syndrome have been reported in preliterature so far. The majority of them are incomplete type of Behcet's disease having intestinal ulceration. Of those, trisomy 8 is the most common chromosomal abnormality. We reviewed similar cases reported and investigated the association of intestinal Behcet's disease with trisomy 8. The association of sacroiliitis with Behcet's disease is also studied.     

Giant cell myocarditis associated with silicone. An unusual case of biomaterials pathology discovered at autopsy using X-ray energy spectroscopic techniques

Silicones, used extensively in the fabrication of medical devices because they were presumed inert and biocompatible, are now well-recognized inducers of localized granulomatous inflammation. Silicones less commonly are also associated with more complex clinico-pathologic entities. In this communication, the authors present a case of a patient on chronic hemodialysis involving tubing probably fabricated from silicone rubber who died from a giant cell myocarditis associated with silicone rubber. This case is presented to expand the interpretive paradigm of human pathology and underscores the need for pathologists to consider medical-device associated phenomena in the differential diagnosis of clinical specimens.     

Multiple organ failure associated with extensive metastatic calcification in a patient with an intermediate state of human T lymphotropic virus type I (HTLV-I) infection: Report of an autopsy case

A patient with an intermediate state of human T lymphotropic virus type I (WLV-I) infection and in whom autopsy showed multiple organ failure (MOP associated with extensive metastatic calcification in systemic organs is described. A 56-year-old man presented with signs and symptoms of advanced cardiac insufficiency, respiratory disturbance and renal failure. Serologically, the anti-human T lymphotropic virus type I (HTLV-I) antibody tier and the levels of both calcium and parathyroid hormonerelated peptide (PTHrP) were dlstinctly elevated. These data suggested a diagnosis of adult T cell lymphoma/leukemia (ATLL). However, examination of a peripheral blood sample revealed only a few atypical lymphoid cells (3%) associated with mild leukocytosis (white blood cell count, 13.7 × 10³/mm³). Lymph node swelling was systemic but mild, with some nodes up to 10 mm In diameter. The patient died of MOF. Adult T cell leukemla/lymphoma was unable to be diagnosed definitively because of the short duration of laboratory abnormalities and because of the discrepancy between the laboratory data and the magnitude of lymphoprollferation in both the lymph nodes and peripheral blood. At autopsy, the most conspicuous finding was extensive metastatic calcification in the multiple organs, including the heart, lungs, kidneys, tongue, liver, pancreas, spleen and systemic arterial walls. Very small numbers of medium-sized atypical lymphoid cells admixed with small reactive lymphocytes were Identified in multiple organs, with no evidence of massive Infiltration. Molecular analyses could not detect monoclonal Integratlon of HTLV-I provirus DNA or monoclonality of T cell lineage cells. Parathyroid hormone-related peptide was demonstrated In the cytoplasm of the atypical lymphoid cells on lmmunohls-tochemical examination. The bone trabeculae generally showed distinct evidence of resorption associated with marked proliferation of osteoclasts. These findings suggested that the hypercalcemia in the present case was categorized as humoral hypercalcemia of malignancy rather than local osteolytic hypercalcemia.     

An unusual variant of T-CLL: evidence for the existence of a hitherto unrecognized T cell subset.

A case of T-cell chronic lymphocytic leukaemia (T-CLL) with an unusual mature membrane phenotype: E+, CD3+, CD4+, CD8-, M1+, Leu-15+, Fc gamma+, is described. The cells were large granular lymphocytes with slight immature features. Functionally these cells lacked helper, suppressor and NK activity but possessed normal levels of K activity. These findings demonstrate several features not previously described in T-CLL: the coexpression of the antigens detected by T4, M1 and Leu-15 the presence of Fc gamma receptors on CD4+ lymphocytes and the lack of NK activity in M1+, Fc gamma+ cells. This study broadens the known heterogeneity of T-CLL and suggests the existence of a hitherto unrecognized normal T-lymphocyte subset with the same functional and phenotypic characteristics as in the case described here.     

An immunohistochemical study of the extracellular matrix in oral squamous cell carcinoma and its association with invasive and metastatic potential

The expression of extracellular matrices (ECMs) laminin (LN), type IV collagen (IV C), heparansulphate proteoglycan (HS-PG), fibronectin (FN), tenascin (TN), decorin and vitronectin (VN) was examined immunohistochemically in 112 primary tumours and 29 metastatic cervical lymph nodes in oral squamous cell carcinoma (OSCC). In highly invasive primary tumours, the expression of LN, IV C and HS-PG in the basement membrane along the tumour-stroma borderline and the expression of decorin and VN in the tumour stroma at the invasive site were all significantly decreased. The expression of FN and TN in the tumour stroma at the same site was markedly increased. In peritumour stroma in metastatic lymph nodes, LN, IV C, HS-PG, decorin and VN were weakly expressed, while FN and TN were strongly expressed. Thus, the staining pattern of the ECMs in the metastatic lymph nodes was similar to that in highly invasive primary tumours. Furthermore, in primary tumours of metastatic cases, the expression of LN, IV C, HS-PG, decorin and VN obviously decreased, while the expression of FN and TN increased when compared with those of the non-metastatic cases. The investigation of ECMs in OSCC was valuable in predicting tumour behaviour.     

Histological evidence of natural killer cell aggregation against malignant melanoma induced by adoptive immunotherapy with lymphokine-activated killer cells

Adoptive immunotherapy with lymphokine-activated killer (LAK) cells and systemic administration of recombinant Interleukin-2 (RIL-2) was carried out in a case of malignant melanoma with lung metastases. Histological specimens from the lung showed a metastatic melanoma heavily invaded by atypical lymphoid cells with convoluted nuclei of varying size. Immunohistochemistry revealed that these cells had the characteristic exclusively of natural killer cell (Leu-7+). Nodules of these cells mimicked the appearance of non-Hodgkin's lymphoma of pleomorphic type. Molecular cytogenetic analysis, however, showed the absence of rearranged bands for the T-cell receptor beta-chain gene, indicating the absence of T-cell clones. At autopsy, 1 month after the LAK therapy, the heavy invasion of convoluted cells had disappeared. These findings clearly indicate that the LAK cell plus RIL-2 therapy induced Leu-7+ lymphoid cells, phenotypically suggestive of natural killer cell aggregation in the tumours.     

The impact of poloxamer 407 on the ultrastructure of the liver and evidence for clearance by extensive endothelial and kupffer cell endocytosis

Poloxamer 407 (P407) is a non-ionic detergent that is used widely in pharmaceutical formulations and personal care products. In animals, P407 causes hyperlipidaemia. P407 is taken up by the liver and causes loss of fenestrations in liver sinusoidal endothelial cells (LSEC), which contributes to the pathogenesis of hyperlipidaemia. Here the short-term (1-15 days) effects of P407 on all liver cells were investigated in mice using electron and light microscopy. As expected, P407 was associated with hyperlipidaemia. Kupffer cells became massively engorged with vacuoles and took on a marked honeycomb morphology. LSECs also became engorged with vacuoles and endocytosis was activated. The diameter of lipoproteins in the space of Disse was less than those in the lumen, consistent with a filtering effect of fenestrations. Defenestration of the LSEC was noted. Hepatocyte endocytosis of lipoproteins and P407 particles was also noted; however, hepatocyte steatosis was not evident. Hepatic stellate cells did not appear to be abnormal. In conclusion, P407 is taken up by the liver mostly through endocytosis by LSECs and Kupffer cells.     

Adenoid squamous cell carcinoma of the skin overlying the right breast. An autopsy case clinically manifested with rapid growth and widely spreading metastases

An autopsy case of a 62-year-old woman with a poorly differentiated, aggressive form of adenoid squamous cell carcinoma arising in the skin overlying the right breast was studied. The tumor, 9 X 8 cm in diameter, had rapidly enlarged since one year before admission from a verrucous lesion of 20 years duration. The histologic features of the tumor showed a well-differentiated squamous cell carcinoma mainly in the superficial areas, which transformed into, with a zone of transition in between, an alveolar or adenoid structure in the deep invading portion. The adenoid tumor cells exhibited an undifferentiated appearance with prominent nucleoli and frequent mitotic figures. These cells partly showed dyskeratotic or acantholytic features. Mucin was negative. The patient died at 8 months after the operation. Autopsy revealed widely spreading metastases in which an adenoid structure was outstanding. These unusual pathological features and an aggressive behavior of this tumor, which were hitherto rarely described for adenoid squamous cell carcinoma, seemed to be a poorly differentiated variant of the tumor. This malignant transformation might be derived from loss of cohesion of the pre-existing usual well-differentiated squamous cell carcinoma in the basal and parabasal layers, inparting marked invasiveness of these cells into the supporting connective tissue.