Nirush Lertprasertsuke

Gastric carcinoma with lymphoid stroma. Analysis using mucin histochemistry and immunohistochemistry

A total of 626 surgically resected gastric carcinomas were reviewed, and 24 cases (3.8%) of “gastric carcinoma with lymphoid stroma” were identified. The tumour cells were consistently arranged in an anastomosing trabecular or alveolar pattern and were densely infiltrated by lymphoid cells. The specimens were studied using mucin histochemistry and the indirect immunoperoxidase method to determine the histochemical properties of this form of gastric carcinoma. The tumour cells were consistently positive for concanavalin A paradoxical staining, class III and almost devoid of acidic mucins, features demonstrating preferential differentiation toward pyloric glands or pseudopyloric glands. Immunohistochemically, positive reactions for Leu M1 and lysozyme, marker substances of (pseudo)pyloric gland cells, were often observed. Carcinoembryonic antigen was positive in focal areas without (pseudo)pyloric glandular patterns. Secretory component was focally positive. HLA-DR was strongly expressed in most cancer cells and 17 tumours (71%) showed positivity for interleukin 1 (IL-1). The lymphoid stroma contained a high percentage of UCHL1-reactive T cells both within and around the cancer cell nests, while SL26-reactive B cells clustered in lymphoid follicles. A considerable number of T-lymphoid cells were also reactive for IL-1. A number of plasma cells with a predominance of IgG-type were distributed around the cancer cell nests. S-100 protein-positive dendritic cells were not identified. We speculate that the prominent lymphoid stroma including intraepithelial lymphocyte-like T cells with IL-1 receptors is possibly induced by IL-1 related mediators released from the HLA-DR-positive gastric cancer cells of the (pseudo)pyloric gland-type.

Alpha-fetoprotein-producing UrachaI Adenocarcinoma

A 45‐year old Japanese male with a history of macroscopic hematuria for more than 6 months presented multiple metastatic lesions in the lungs. Cystoscopic examination demonstrated a large tumor mass protruding from the dome of the urinary bladder. Ultrasonography and CT highlighted a solid and cystic urachal tumor continuous from the vesical dome to the navel. Serum levels of alpha fetoprotein (AFP) and carcinoembryonic antigen (CEA) were elevated to 17, 100 ng/ml and 17.7 ng/ml, respectively. He underwent palliative curettage of the vesical dome tumor twice, followed by chemotherapy with little effect. One year after admission, he died of progressive metastases to the lungs, left pleura, liver and brain. Final serum levels of AFP and CEA were 86, 200 ng/ml and 60.9 ng/ml, respectively. The tumor was histologically classified as adenocarcinoma with a medullary growth pattern. Both papillotubular and solid (hepatoid) components were observed. The cancer cells were rich in glycogen and were immunoreactive diffusely for AFP and focally for CEA. CA15–3, CA19–9, epithelial membrane antigen and cytokeratin were also positive. In addition, argyrophilic cancer cells with immunoreactivities of neuron‐specific enolase, chromogranin A and peptide YY were demonstrated. To our knowledge, this is the first reported case of AFP producing adenocarcinoma of urachal origin.

Latent Perianal Paget's Disease Associated with Mucin-producing Rectal Adenocarcinoma Report of Two Cases

Two cases of latent perianal Pagets disease associated with mucin producing papillary adenocarcinoma of the rectum are described. In both cases, the rectal tumors appeared as polypoid lesions located just above the dentate line. The adjacent anal squamous mucosa showed lateral invasion of alcianophilic mucin‐containing Paget cells. Mucin histochemistry revealed the presence of 0 acylated and non‐0 acylated sialic acids in both neoplastic goblet cells in the adenocarcinomas and Paget cells in the anal mucosa. The Paget cells were immunoreactive diffusely for low molecular‐weight cytokeratin (CAM 5.2) and car‐cinoembryonic antigen, and focally for CA19 9, epithelial membrane antigen and CA15 3. All these substances were also expressed in the rectal adenocarcinomas but were negative or showed limited expression in the anal squamous epithelium. These findings indicated secondary epidermotropic infiltration of neoplastic goblet cells from the rectal adenocarcinomas.

Rectal carcinoid tumor metastasizing to the thyroid and pancreas. An autopsy case exploiting immunohistochemistry for differentiation from tumors involving multiple endocrine organs.

A 58‐year‐old male patient with rectal carcinoid tumor is presented. The tumor extensively involved the lymph nodes and liver, and multiple tumors were also recognized in the pancreas and thyroid. Grossly, it was uncertain whether the latter were metastases from the rectal carcinoid or all were coincident primary tumors involving multiple endocrine organs, so‐called multiple endocrine neoplasia (MEN) syndrome. Histologic, histochemical and electron microscopic examinations of the tumors in both the pancreas and thyroid showed similar features to those of the rectal carcinoid. The neoplastic cells in all involved organs commonly expressed positive immunoreactivity for somatostatin, but negativity for carcinoembryonic antigen, calcitonin, calcitonin gene‐related peptide, thyroglobulin, insulin, glucagon and pancreatic polypeptide. These immunohistochemicai results confirmed that the tumors observed in multiple endocrine organs were indeed metastatic from the rectal carcinoid, rather than being a new combination of MEN syndrome. Some neuroendocrine tumors may develop widespread metastasis, sometimes creating problems with differentiation from multiple primary endocrine tumors. lmmunohistochemistry may be of great help in setting this issue.

Different Effects of Carbon Tetrachloride on Carcinogen–induced Hepatocellular Carcinoma and Normal Liver of the Rat: Lowered Lipid Feroxidation and Accelerated Necrosis in Cancer

To investigate molecular responses to lipid peroxidative stimuli in neoplastic cells, lipid peroxidation was induced in liver of rats bearing 3′‐methyl‐4‐dimethylaminoazobenzene‐induced hepatocellular carcinoma by injecting a high dose of carbon tetrachloride (CCL4), a strong lipoperoxidative reagent. Normal rat livers with or without CCl4 treatment served as controls. CCL4, administration markedly provoked fatty metamorphosis, visualized by oil red O staining, in normal livers while minimal fatty changes were seen in hepatocellular carcinomas, where necrosis was often observed instead. After CCl4 treatment, the thiobarbituric acid values (representing levels of lipid peroxides in the tissue) were increased two–fold in the untreated normal liver, but were unchanged in the cancer tissue. Levels of vitamin C, an acutely reactive antioxidant, measured by high‐performance liquid chromatography were not influenced by the CCL4 injection in the cancer tissue whereas a significant decrease was evident in normal livers. The total fatty acid content, measured by gas chromatography, was significantly lower in the cancer tissue than in the normal liver while the ratio of polyunsaturated fatty acids (PUFAs) in total fatty acids was little changed. Resistance of hepatocellular cancer cells to fatty metamorphosis and their susceptibility to necrosis induced by free radicals may be due to the paucity of the target PUFAs in their cell membrane fraction, resulting in low levels of lipid peroxides. Peroxidation of PUFAs might act as a “shock absorber” against free radical‐induced toxic cell death in normal cells.

C Cell Carcinoma of the Thyroid Follicular variant

A case of C cell carcinoma of the thyroid with an unusual follicular growth pattern of the cancerous C cells is described. The primary tumor consisted of a mixture of medullary and follicular features while the metastatic foci in the lymph nodes and liver displayed only a medullary arrangement. Histochemical study disclosed numerous argyrophilic cells in both the follicular and medullary parts. These cells were immunohistochemically positive for calcitonin, calcitonin gene‐related peptide (CGRP) and other peptides as well as carcinoembryonic antigen (CEA), but negative for thyroglobulin. Radioimmunoassay done on the tissue extract revealed a high content of calcitonin. Electron microscopy showed small intracytoplasmic secretory granules and, in the follicular lining cells, formation of microvilli. A minor component consisting of glandular structures has been reported in medullary carcinoma of the thyroid, suggesting a potentiality for glandular differentiation of the C cells. In equivocal cases, immuno‐histochemical examination for calcitonin and thyroglobulin is essential for accurate diagnosis of thyroid carcinoma. Acta Pathol Jpn 39: 393‐399, 1989.

B‐cell Lymphoma with Vimentin‐positive Cytoplasmic Inclusions

A 60‐year‐old woman complaining of cervical lymph‐adenopathy was admitted to Keiyu General Hospital, Yokohama. Malignant lymphoma involving systemic lymph nodes and the bilateral tonsils was suspected by computed tomography. The biopsy diagnosis of the cervical lymph nodes was B‐cell lymphoma, diffuse medium‐sized cell type. The cleaved centrocytic lymphoma cells were immunoreactive for CD20 and CD22 but negative for immunoglobulins. Characteristically, a considerable number of neoplastic lymphocytes possessed eosinophilic round inclusions in the cytoplasm. The inclusions were green in color by Papanicolaou staining, whereas they appeared vacuole like in Giemsa‐stained preparations. Ultrastructural study confirmed the presence of aggregates of intermediate‐sized filamentous structures mainly in the perinuclear area. The rough endoplasmic reticulum and Golgi apparatus were poorly developed. Immunocyto‐chemical staining using cytologic specimens and fresh‐frozen sections disclosed that the inclusions were composed of vimentin filaments. Morphologic similarities to signet ring cell lymphoma are discussed. Acta Pathol Jpn 41: 473 479, 1991.

An Unusual Form of Chronic Myeloproliferative Disorder Aleukemic Basophilic Leukemia

A 52‐year‐old Japanese man manifested various clinical signs and symptoms such as vomiting, high fever, dyspnea, cough, sweating, palpitation, eosinophilic leukocytosis and hepatosplenomegaly. These histamine related clinical manifestations showed a dramatic response to steroid therapy. After 10 months of hospitalization, he suddenly succumbed to candidal septicemia at the end of the third cycle of steroid therapy. Autopsy revealed neoplastic proliferation of immature basophils in various internal organs without involvement of the skin. The neoplastic cells, positive immunohistochemically for leukocyte common antigen, possessed lobulated nuclei and weakly metachromatic cytoplasmic granules, predominantly of the basophil type, which exhibited weak naphthol ASD‐chloroacetate esterase activity. Mast cell type granules were also observed ultrastructurally. The neoplastic infiltration was associated with fibrosis in the liver, spleen and bone marrow and with extramedullary hematopoiesis in the liver, spleen, lymph nodes and perihypophyseal tissue. The bone marrow showed uneven and multifocal involvement. Despite the lack of leukemic manifestations and the results of chromosomal analysis, the most suitable diagnosis was aleukemic basophilic leukemia within the category of chronic myeloproliferative disorder. Kinship of this neoplasia to systemic mastocytosis is discussed. Acta Pathol Jpn 41: 73 81, 1991.

An Autopsy Case of So‐called Midline Malignant Reticulosis Followed by Extensive Dissemination with Immunohisto‐chemical Evidence for Its T Cell Malignancy

An autopsy case of malignant midline reticulosis (MMR) is reported. The patient, a 42 year old Japanese male, died after a clinical course of 22 months. Autopsy revealed extensive infiltration of generalized organs by the tumor cells, suggesting that the disease was highly malignant in nature. Staining with monoclonal antibodies against T cell surface antigens Leu 4 on frozen sections and UCHL1 on paraffin embedded sections enabled us to examine the phenotype of the tumor cells with good morphological preservation and to verify the T cell nature of the tumor. Acta Pathol Jpn 39: 446 450, 1989.