V. Desmet

Leukemia-associated lymph node infiltrates of plasmacytoid monocytes (so-called plasmacytoid T-cells): evidence for two distinct histological and immunophenotypical patterns

The medium-sized mononuclear cell with plasmacytoid features, formerly known as “T-associated plasma cell” or “plasmacytoid T cell,” has recently been shown to express several myelomonocyte and monocyte-macrophage associated antigens, suggesting a monocytic origin, and it has been renamed “plasmacytoid monocyte.” The present study describes the clinical and pathological features of two patients with generalized lymphadenopathy and leukemia (chronic myelomonocytic leukemia in Case 1, and acute non-B, non-T lymphoblastic leukemia in Case 2), and whose lymph node biopsies showed large numbers of plasmacytoid monocytes associated with the leukemic infiltrates. Case 1 was strikingly similar to three previously reported cases of so-called “plasmacytoid T cell” lymphoma, all associated with a myeloproliferative disorder. In our case, the destructive growth pattern of the plasmacytoid monocytes and the de novo expression of CD5 on these cells favored their neoplastic nature; the sharing of some markers of plasmacytoid monocytes with the myelomonocytic infiltrate suggested they were part of the tumoral proliferation. In Case 2, plasmacytoid monocytes displayed an immunophenotype guide similar to that reported in reactive conditions and were antigenically unrelated to the leukemic cells; plasmacytoid monocyte clusters occurred also in the lymphoid parenchyma spared by the leukemic infiltrate. These findings led us to interpret the large numbers of plasmacytoid monocytes in this second case as a tumor-associated host reaction.

Arsenic and non-cirrhotic portal hypertension: A report of eight cases

It was discovered that eight patients with complications of non-cirrhotic portal hypertension had received an arsenical preparation for psoriasis as Fowlers solution some years age. Seven of them were admitted for bleeding oesophageal varices. Upon admission, splenomegaly and hypersplenism were present. Liver tests were normal and palmar skin keratosis and melanosis were noted. Liver biopsy of six patients showed features of incomplete septal cirrhosis. Malignant skin lesions were present in half of the patients. One patient died from lung carcinoma and another from an ovarium neoplasm. Chronic arsenic intake should be actively looked for in all patients with psoriasis and non-cirrhotic portal hypertension. They should be followed up for many years for development of malignant lesions in skin, lung and liver. Liver abnormalities present in the biopsies are often minor and may escape detection.

Morphological identification of alpha‐I‐antitrypsin in the human small intestine

Alpha‐I‐antitrypsin immunoreactivity was demonstrated by immunofluorescence in epithelial cells of the normal human small intestine. Its presence was also confirmed in biopsies of patients with Crohns disease. Specific fluorescence was observed in only four out of 14 adult patients with coeliac disease. These results implicate the human small intestinal epithelium as a possible source of alpha‐I‐antitrypsin. The absence of positive cells may have implications in the aetiology of coeliac disease.

Merkel cell tumor of the skin: An immunohistochemical study

Skin biopsy specimens from 12 elderly patients with Merkel cell tumors were investigated. Conventional light microscopy and immunohistochemical techniques were used. All of the tumors had similar morphologic features. Immunoreactivity for neuronspecific enolase, gastrin, calcitonin, and epithelial membrane-like antigen was demonstrated, and both neurofilaments and keratin filaments were observed. The immunohistochemical findings supported a Merkel cell origin for these Merkel cell tumors. The co-expression of neuroendocrine and epithelial markers in Merkel cell carcinomas is suggestive of neuroendocrine differentiation in a neoplasm of epithelial origin. Merkel cell carcinomas share many characteristics with neuroendocrine tumors of the bronchopulmonary and gastrointestinal tracts. All of these neoplasms may originate from cells of similar types that are present in several organs.

Lymphocytes and Langerhans cells in the human oesophageal epithelium.

Using monoclonal antibodies on fresh frozen endoscopically obtained oesophageal biopsies the distribution of Langerhans cells, B lymphocytes, and various subpopulations of T lymphocytes was studied in the normal human oesophageal mucosa and in oesophagitis. Identification of the lymphocytes was carried out by an immunoperoxidase technique using OKT3 (antihuman T cell antibody), OKT4 (antihuman helper T cell antibody), OKT8 (antihuman cytotoxic T cell) and OKT10 (antihuman null cell antibody). Identification of the Langerhans cells was carried out using an ATPase stain and OKIa (Ia like antigen) and OKT6 (antihuman thymocyte). In the normal oesophageal epithelium cytotoxic T lymphocytes are found as well as Ia positive Langerhans cells. Helper T lymphocytes and B lymphocytes are present mainly in the lamina propria. In oesophagitis an increase in Langerhans cells and cytotoxic T lymphocytes within the epithelium is found. From these findings it can be concluded that the oesophagus contains a reticuloepithelial system as well as a lymphocytic population which are a part of the gut-associated lymphoid tissue.

Electron microscopy and histochemistry of canalicular differentiation in fetal and neonatal rat liver

Abstract The differentiation of the biliary pole of the hepatocyte was studied during development. Four successive types can be distinguished morphologically. Type I, found at 16 days of fetal life, is formed by an intracytoplasmic invagination of the cell membrane. At 19–20 days, most canaliculi correspond to type 2, formed by sequestration of cytoplasmic fragments. In the perinatal period most canaliculi are of type 3, characterized by a wide and regular lumen, without microvilli. From the 2nd day of life on, an increasing number of canaliculi acquire microvilli and correspond to type 4. Histochemical results after incubation for alkaline phosphatase further support the proposed maturation scheme. The morphologic and histochemical characteristics of type 3 canaliculi suggest the existence of a cholestatic phenomenon of the neonatal liver.

Reactive human bile ductules express parathyroid hormone-related peptide

Various cholestatic liver diseases as well as regeneration after submassive necrosis are accompanied by a striking increase in the number of bile ductules. These reactive bile ductules are thought to arise either from proliferation of pre‐existing bile ductules or bile ductule‐related facultative stem cells, or from ductular metaplasia of hepatocytes. Recently, we found that reactive bile ductules display neuro‐endocrine features, and speculated that the substance(s), produced in the neuro‐endocrine granules, might play a role in their growth and/or differentiation through an autocrine or paracrine pathway. Parathyroid hormone‐related peptide has been shown to be encoded by a growth factor‐regulated gene that may play a role in cell growth and differentiation. We studied the immunohistochemical expression of this peptide in human liver, including three normal biopsies, 11 cases of cholestatic liver disease, six cases of focal nodular hyperplasia and three cases of regenerating liver. In regenerating liver, primary biliary cirrhosis, primary sclerosing cholangitis and partial or intermittent obstruction, the majority of reactive ductular cells expressing neuro‐endocrine markers also expressed parathyroid hormone‐related peptide. In focal nodular hyperplasia, a smaller number of bile ductular cells expressed the peptide. These findings suggest that parathyroid hormone‐related peptide is localized in bile ductular cells and may indicate a role for this hormone in the growth and/or differentiation of human reactive bile ductules.

A recommended procedure for ultrastructural immunohistochemistry on small human tissue samples.

Various fixation and staining procedures for the demonstration of surface and cytoplasmic antigens have been described. An immunostaining procedure was sought that would allow the demonstration of these antigens, especially in small human tissue samples at the ultrastructural level. A modification and adaptation of the technique of Eldred, Zucker, Karten, and Yazula (J Histochem Cytochem 31:285, 1983) was applied on several varieties of human tissue, including liver, skin, and lymphoid tissue, using monoclonal and polyclonal antibodies in an indirect peroxidase procedure. In this way a reliable and generally applicable procedure was developed that satisfied the following demands: Use of a universal fixative that allows preservation of the antigenicity of various antigens; Adequate penetration of the tissue by the immunological reagents; Optimal preservation of subcellular structures; and Possibility to store the tissue samples for considerable periods of time.

Parathyroid hormone-related peptide expression in primary and metastatic liver tumours

Parathyroid hormone‐related peptide (PTHrP) is a major factor in the pathophysiology of hypercalcaemia of malignancy. Recent evidence suggests that PTHrP may play an important role in the growth and differentiation of neoplastic as well as non‐neoplastic cells. PTHrP was originally detected in normal fetal, but not adult, liver. We have used immunocytochemistry to show that reactive human bile ductules expressing a neuroendocrine phenotype contain immunoreactive PTHrP. These observations raised the possibility that PTHrP immunoreactivity may be useful in the differential diagnosis of primary liver tumours and metastases of adenocarcinoma. A total of 24 primary liver tumours and 22 metastases of adenocarcinoma were studied. All cholangiocarcinomas showed immunopositivity for PTHrP and chromogranin A, while all hepatocellular carcinomas were negative for PTHrP and showed only focal and weak positivity for chromogranin A. Mixed types of primary liver tumour contained PTHrP immunoreactivity only in the areas of cholangiocellular differentiation. Moreover, all metastatic adenocarcinomas were negative for PTHrP and chromogranin A except for two out of five metastatic breast adenocarcinomas. These two patients had bone metastases and hypercalcaemia and thus did not yield differential diagnostic problems with cholangiocarcinoma. None of the patients with cholangiocarcinoma and hepatocellular carcinoma had hypercalcaemia. We conclude that PTHrP is a useful marker for primary cholangiocarcinoma. especially in the differential diagnosis of hepatocellular carcinoma and metastatic adenocarcinoma.

Immunopathology of trachomatous conjunctivitis.

Upper palpebral conjunctival biopsy specimens obtained from eight patients with active trachoma were examined by routine histological and immunohistochemical methods. The epithelium expressed class I major histocompatibility complex (MHC) products throughout and class II MHC products in the superficial layers. The epithelial inflammatory infiltrate consisted of polymorphonuclear leucocytes, macrophages, T lymphocytes, and dendritic cells. In the underlying stroma the inflammatory infiltrate was organised as B lymphoid follicles, and there was also a diffuse infiltrate consisting of plasma cells and scattered B lymphoid cells, dendritic cells, T cells, macrophages, and polymorphonuclear leucocytes. Each type of cell has its special location in the tissue. Plasma cells were located on a subepithelial band and as a dense infiltrate round the acini of accessory lacrimal glands. IgA+ plasma cells outnumbered IgG+ cells, whereas IgM+ and IgE+ cells were few. Our data provide good evidence for the presence of both humoral and cell mediated immune responses and a possible role for autoimmune mechanisms in the conjunctival tissues of trachoma patients.