Search

Ten cases of Medullary carcinoma of Thyroid gland (MCT) were examined (two familial, eight sporadic) in patients with increased serum calcitonin levels and ranging age from 31 to 87 years. Immunocytochemical reactions were performed using Peroxidase-Antiperoxidase (PAP) complex and/or Avidin-Biotin-Peroxidase complex (ABC) by light microscopy on fixed tumorous specimens (10 cases) and additionally by electron microscopy (3 cases). The tumors displayed light microscopic features typical of MCT. The cells were polyhedral, angular or fusiform and showed high affinity for Grimelius stain. Large deposits of amyloid were Congo red stained and disclosed a green birefringence in polarized light. In the familial cases sections of non-tumorous thyroid tissue showed C cell hyperplasia. Electron microscopic studies revealed intracytoplasmic secretory granules and amyloid fibrils. The immunoperoxidase technique demonstrated calcitonin in the tumor cells in all the cases, with a weaker staining than in para-and intra-follicular C cells of adjacent non tumorous tissue and than in C cells hyperplasia foci, when present. Immunoreactive tumor cells were also observed with anti SRIF in 4 cases, with anti-ACTH and anti-beta MSH in 3 cases, and with anti-beta endorphin in 2 cases. These results are discussed with a review of the literature.

Anatomo-clinical findings are reported in a case of central nervous system degeneration which began at age 47 and progressed over a three year period. Information obtained prior to the patient's death suggested probable spinocerebellar degeneration with amyotrophies. Postmortem anatomical examination confirmed this diagnosis but also revealed the existence of unsuspected lesions. These clinically non-manifested lesions involved severe pallido-luysian degeneration as well as numerous and diffuse senile plaques. The nosological implications of this case are discussed.

Estrogen receptor (ER) immunocytochemical assay (ER-ICA) was assessed human breast carcinomas. The patient's age, the tumor size, the histological type and SBR grade, the presence or the absence of axillary lymph node metastases and of vessel invasion in tumor borders were recorded in all the cases included in the series (n = 469) estrogen and progesterone receptors were concomitantly evaluated (DCC method) and or immunoenzymatic assays. Monoclonal H222 sp gamma and PAP procedure (Abbott kit) were applied in frozen sections, tumor imprints and fine needle aspirates. A computerized system of image analysis referred to as SAMBA (TITN), permitted to achieve a multiparametric quantitative analysis of ER positive surfaces. With this system, in each tumor, the cellularity, the percentage ER surface versus the total cell surface and versus the epithelial (keratin positive) surface, integrated optical density (IOD), mean optical density, index of the concentration of labelled objects, and IOD histograms, were obtained and correlated to histological and biochemical data. It was shown that: 1) ER antigenic sites were heterogeneously distributed in ER positive tumors, with a specific nuclear localization in epithelial cells; 2) the SAMBA 200 multiparametric analysis of the ER sites distribution in tissue was appropriate, accurate, reproductible and therefore more reliable than the semi-quantitative analysis; 3) the standardization and the complete automation of this method of immunoprecipitates evaluation on tissue section permit to daily and to routinely analyse a large number of preparation; 4) there was a correlation between ER binding sites evaluation (DCC) and ER antigenic sites immunodetection (ER-ICA and ER-EIA); 5) there was a correlation between the SAMBA evaluation of ER-ICA and other histological prognostic factors such as small tumor size, low SBR grade, the absence of axillary lymph node metastasis and vessel invasion; 6) the preliminary SAMBA analysis of ER-ICA in tissue sections, imprints and fine needle aspirates suggest that fine needle aspirates may not reflect accurately the tumor cell heterogeneity.

The practical applications of computer-assisted image analysis systems are multiple in oncology. The computerized system of image analysis referred to as SAMBA (TITN) is particularly relevant to analyse coloured images resulting from immunostaining or histochemical procedures assessed either on tissue sections of any type or cytological preparations (imprints, smears). The SAMBA analysis of positive Ki67 surfaces in tissue sections from breast, endometrial, ovarian, cervical or urinary bladder samples enables a multiparametric evaluation of the growth fraction (GF) in intraepithelial, borderline or invasive proliferations. Moreover, the SAMBA analysis after Feulgen staining procedures provides a parametric evaluation of the nuclei densitometry and morphological features and of the chromatin texture, which serve to compute the ploidy balance (BP) and the proliferation index (PI). In benign tumors, GF and PI are low and tumor cells are diploid with an overall high positive PB values. In malignant tumors, GF, PI and the percentage of aneuploid cells increase with tumor grade and stage whereas PB decreases. In borderline proliferations, FC, PI and PB intermediate values are recorded. These new criteria of prognosis should be assessed routinely in pathology departments and the results from these new investigations are likely to be soon implicated in the selection of patient therapy.

Twenty-three cases of primary brain lymphomas were morphologically studied. Electron microscopy was done in twelve cases and immunoperoxidase reactions for light chains of immunoglobulins in ten cases. The patients were fourteen males and nine females. Except two children, the mean age was 50 years. Clinical features and pre-operative investigations lacked any specificity. Post-operative radiotherapy could be performed in thirteen patients, eleven of them being still alive with a follow-up varying from 2,5 months to 4,5 years. All the other patients persued fulminating course (max: 4,5 months). Tumors were preferentially located in frontal and temporal lobes. On gross examination, well limited tumors were more frequent than ill-defined or purely infiltrating tumors. Microscopically, all the lymphomas were of the diffuse type. Perivascular clusters of lymphoma cells, meningeal and parenchymal infiltrates and sub-ependymal sprouts were found in the peritumoral areas. The lymphomas were cytologically characterized according to the modified Kiel classification (Lennert et al, 1975) using light and electron microscopic data. So were identified thirteen lymphoblastic lymphomas (with one convoluted-cell type), one centroblastic lymphoma, eight immunoblastic lymphomas (two with plasmacytic differentiation). Light chains of human immunoglobulins were immunocytologically demonstrated in six of twelve tumors tested, all the positive cases corresponding to immunoblastic lymphomas. A unique case of primary meningeal Hodgkin's disease was found. These results were compared with the rare previous reports associating these different morphological investigations.

A wide range of normal human tissue samples including cervix, endometrium, thyroid, pancreas, parotid, breast, placenta, gastric mucosae, striated muscle were compared with tumorous and non tumorous disorders (thyroiditis, Graves disease, follicular adenoma, thyroid carcinomas, breast cystic disease, fibroadenoma, adenosis, breast carcinomas) using anti-laminin and Avidin Biotin Peroxidase complex method on frozen sections (light microscopy study) and vibratome cut 100 micrometer-thick-sections (electron microscopy study). It was shown that laminin was located in the lamina densa of basement membranes (BM) in normal human tissue and visible on BM like structures around decidua cells, BM were abnormally thick and often multilayered but continuous and laminin positive in intraductal breast carcinomas and well differentiated follicular carcinomas of thyroid, in invasive carcinomas laminin immunostaining displayed an heterogeneous pattern with disruptions and even may completely disappeared, in tumor stroma, blood vessels BM had a laminin abnormal staining with a multilayered pattern. Since laminin is involved in cell attachment to basement membrane through specific receptors to laminin and to biochemical components of modified interstitium found in tumorous disorders, laminin immunohistochemical detection constitutes a valuable method for a better understanding of tumor cells diffusion and metastases development.

In the present study the immunodetection of various markers in a large series of tissue samples have been analysed through the computerized system of image analysis referred to as SAMBA 200. The immunodetection of estrogen and progesterone receptors, Laminin and type IV collagen, Ki 67, keratin, papilloma virus have been performed in frozen sections or in imprints and fine needle aspirates from tumorous and non tumorous disorders of human breast, endometrium, cervix and ovaries. Staining procedures varied with the type of the marker studied (PAP, ABC-P, ABC-GO, APAAP). The results obtained by the multiparametric SAMBA analysis were accurate, reproducible and reliable. Therefore, the SAMBA analysis providing a standardized and automatic analysis of immunodetection performed in tissue sections can be routinely used in pathology laboratories particularly for the prognostic evaluation and for the prediction of hormonotherapy and chemotherapy response of patients with solid malignant disorders.

The central nervous system (CNS) has no true lymphatic outflow and is protected by the blood-brain barrier. It shares special relationships with the immune system. Though heterologous grafts can sometimes survive inside the brain, explaining that it has been considered as an immunologically privileged site, the CNS is able to generate immunological immune reactions and can exert a regulatory role on the extracerebral ones. Inside the brain, the immunological reactions are probably due to populations of immunocompetent cells and potentially macrophagic cells which are there permanently but in an inactivated state. Nevertheless the first event triggering these reactions and responsible for the activation of immunocompetent cells remains highly hypothetical. The astrocyte-endothelial cells complex which is the anatomical support of the blood-brain barrier probably plays a vital role in this process. Permanent exchanges between the CNS and the immune system are assumed by soluble mediators: lymphokines, neurotransmitters and hormones. These allow the CNS to control to some extent the extracerebral immunological reactions by feed-back regulation mechanisms.

Among 980 sural nerve biopsies, the nerves of 10 patients showed a great number of focal sausage-shaped thickenings of the myelin sheaths and were investigated by light and electron microscopy, teasing and quantitative studies. Single teased nerve fibres revealed myelin thickening in more than 25 p. 100 of internodes. This condition defined the tomaculous neuropathy and differed from other degenerative or toxic neuropathies which displayed a small number of internodes with myelin thickenings, in less than 5 p. 100. Segmental demyelination and remyelination were found in 12 p. 100 to 65 p. 100 of myelinated fibres. Tomaculous swellings were observed in the internodes of these fibres. Except axonal constriction within the sausage-shaped thickenings, no fibers with axonal degeneration was observed. The density of myelinated and unmyelinated fibres was normal. The loss of large myelinated fibres was interpreted as resulting from the myelinic changes. Clinical and electrophysiological data were similar in the ten cases of tomaculous neuropathies and in hereditary neuropathy with liability to pressure palsies, i.e.: autosomal dominant inheritance, higher incidence in males, recurrent nerve trunck and/or brachial plexus involvement related to compression, slowing of nerve conduction velocities in clinically affected and unaffected nerves more pronounced in anatomical narrow sites and increased F wave latencies. One patient (case 10) showed a mixed sensory motor progressive neuropathy but signs of widespread neuropathy were noted in more advanced cases. A great number of tomaculous swellings of myelin sheaths is considered as a specific but non constant change of hereditary neuropathy with liability to pressure palsies.

A case of peripheral neuropathy following cimetidine treatment is reported. Four days after beginning cimetidine (200 mg four times a day), the patient developed muscle pain and a symmetric motor neuropathy in all 4 limbs, predominant distally and in the lower limbs. Cimetidine was discontinued. Within seven days motor function began to return and within five months recovery was complete. Electrophysiological studies showed an axonal neuropathy. Morphometric studies revealed loss of large myelinated fibers in some fascicles while other fascicles were normal. Teasing studies showed predominant axonal lesions. Microvasculitis was present in the epineurium. Such findings suggest a role for small-vessel immune-complex vasculitis in the pathogenesis of this cimetidine-induced peripheral neuropathy.

The case of 65 year old woman with progressive enlargement and "wooden" induration of the pelvic girdle and thigh muscles due to an amyloid infiltration is reported. Muscle changes appeared two years after a diagnosis of myeloma with free lambda light chains. The patient complained of muscle pain, lassitude and weakness. Macroglossia was present. Skeletal muscle (vastus lateralis) contained large amounts of amyloid substance and showed type 2B atrophy. There was no fiber type grouping. Some amyloid deposits abutted on the muscle fiber, destroyed the basal lamina and sarcolemma, but never infiltrated it. Besides the amyloid phagocytosis by macrophages, a relationship between amyloid filaments and fibroblasts was present. Another non-congophilic substance was revealed using the Avidin-Biotin peroxidase complex to localize lambda light chains by light microscopy and corresponded to a granular substance in electron microscopy. Clinicopathological results are discussed with a review of thirteen similar cases previously reported.

The authors report a case of enteropathy due to clofazimine treatment for prurigo nodularis. The drug usually restricted to the treatment of leprosy has sometime been given to patients suffering from skin diseases because of its assumed anti-inflammatory effects. When high dosage of clofazimine treatment is carried on during a long period, and drug accumulates in the tissues and precipitates as a solid. This crystal storage in the lamina propria of the jejunal mucosa and in the mesenteric lymph nodes accounts for an enteropathy, sometime severe but slowly regressing after drug withdrawal. The electron microscopic study shows the prints of these crystals in autophagic vacuoles of histiocytes.

The technological features of multiple and simultaneous assays of steroid receptors (estrogen and progestagens) have been considered in human mammary carcinomas. Most of the parameters involved in the accuracy and the fiability of S-R determination have been investigated : the stability of S-R proteins (collection and storage of sample, cytosol preparation and buffer components, endogenous steroid problem), the specificity and precise quantitation of the binding (conditions of incubations, use of steroid analogs, dextran-coated charcoal method and treatment of binding data by the Scatchard analysis), the identification of the binding (vertical sucrose density gradients) and the interferences in DCC assays. The routinely adopted protocol has been experienced in 650 cases of S-R assay. It is concluded that when performed under appropriate and properly controlled conditions and even in a small sample, multiple S-R assay could result in a precise quantitation and identification of the pathological state of the S-R system in a tumor at time of surgery. Considered with regards to actual knowledges in cell biology, that is of importance and could provide even more information about therapeutic guidance.

Endogenous sources of prostaglandin production in human breast tumors were investigated by radioimmunoassay analysis of PGE2 and PGF2a productions and 3H-PGE2 conversion. PG synthetase located within the microsomal fraction mainly produced PGE2, while little PGF2a synthesis occured. In cytosol preparations. PGE2 is converted into PGF2a. In 15 tumor specimens, no relationship was observed between PGE2 production and the metabolic activity which varied widely from sample to sample. These findings demonstrate the presence of PG-9-keto-reductase in the cytosol from human breast tumors. A way of PGE2 inactivation by this enzyme is suggested since no less polar PGE2 metabolites were detected. It is concluded that PGE2 production by the microsomes will reflect the PG synthetase activity of a given human mammary carcinoma while metabolic conversion of PGE2 within the cytosol reflects the metabolic activity of the same sample. Both activities were otherwise apparently unlinked.

A 34-year-old man developed cerebellar symptoms, palatal myoclonus and spastic paraparesis progressing over several months. During this period, acute respiratory failure occurred in two instances with evidence of central chronic hypoventilation. CT scan showed enlargement of the frontal horns and posterior fossa cisterns. Post mortem examination revealed the following features: 1) Rosenthal's fibers widespread throughout the CNS but especially in subependymal regions; 2) bilateral white matter cavitations involving the frontal lobes, hilum of dentate nuclei and bulbar pyramids; 3) microscopic pseudogliomatous foci present in several sites, especially in the fornix and midbrain tegmentum; 4) the medulla and high cervical spinal cord showed "peripheral type" myelin fibers along with Schwann cell proliferation in aberrant intra-parenchymal situation. The relationship of this case--as well as the few previous adult reports--to the well-defined infantile Alexander's disease is discussed. The possible hamartomatous nature of both glial changes and aberrant myelin production is emphasized. These various lesions, including Rosenthal fiber formation, are assumed to result from a similar--probably dysontogenetic--pathophysiological mechanism. It is suggested that Alexander's disease, in this case, should be classified among phakomatoses rather than enzymopathic leukodystrophies.