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Anatomico-clinical, histologic and ultrastructural data of a case of neurofibromatosis of the bladder are reported. The principal cells of the neurofibroma appear isolated in the intercellular substance and have thin cytoplasmic processes, vacuoles, microfibrils, dense osmiophilic bodies and occasional ergastoplasmic tubules. Moreover, the presence of intracytoplasmic axons, a basement lamina of thickened amorphous periplasmalemmatic material and cilia support the theory of the Schwann cell origin of these cells. On the basis of these observations, the hypothesis that neurofibroma, in contrast to neurinoma, arises from the Schwann cells of unmyelinated nerve is advanced.

Spontaneous lymphoma developed in 57 % female SJL/J mice, with a mean latent period of 58 weeks and in 33 % male SJL/J mice with a mean latent period of 72 weeks. In (CBA x SJL) F1and F2, the incidence in females was 79 % and 67 % at a mean age of 107 and 100 weeks respectively while in males it was 53 % and 41 % at 111 and 106 weeks. In reciprocal F1and F2hybrids, an incidence of 62 % and 37 % was observed in females at 118 and 109 weeks of age, while in males it was 33 % and 43 % at the mean ages of 72 and 90 weeks. Gross lesions were usually restricted to mesenteric, cervical, axillary and inguinal lymph nodes, Peyer's patches and spleen. Less frequently, lungs, liver, kidney and thymus were also involved. Histological examination of nodes in the pre-neoplastic stage revealed follicular hyperplasia with prominent germinal centers, sinus hystiocytosis, precence of pyroninophilic cells within the paracortical area and medulla, medullary plasmocytosis and epithelioid sarcoid-like noduli. Nodes, spleen and other affected organs examined during overt disease showed a pleomorphic pattern characteristic of type B reticulum cell neoplasm according to Dunn and contained predominantly plasma cells, giant cells or reticulum cells. At the electron microscope, these different cell types were detected within the neoplastic tissue. In addition, cells resembling immunoblasts were frequently observed, which suggests that they might represent proliferating tumor cells capable of differentiating into plasma cells. Type C-immature and A intracisternal particles were repeatedly observed, but no type C-mature particles were seen. Attempts to transplant neoplastic tissue in syngeneic hosts were successful. Cell-free extracts from primary SJL/J lymphomas were injected in newborn RFM and CBA mice. 4 out of 9 RFM mice developed SJL/J-like lymphoma at 64–70 weeks of age, while no lymphomas were found in 8 CBA mice over 70 weeks of age. Freund adjuvant injected intraperitoneally in (CBA x SJL/J) F1mice did not modify the incidence or the latency of the lymphomas when compared with control animals.

Extramedullary plasmocytoma is a tumor chiefly located in the upper air passages and oral cavity, usually characterized by a slow rate of growth and lack of the biochemical data distinctive of multiple myeloma. Eight cases of extramedullar plasmocytoma are reported, six located in the nasal cavity, one in the maxillary sinus and one in the oropharynx, and the relevant histological features are described: the pyronin affinity of cells, more evident at pH 4.8, was constantly positive; the Russell bodies and the Mott cells, similar to those seen in plasmacell granulomas, were seldom present; the argyrophylic reticulum was rather regular and generally with alveolar pattern; the stainability with the amyloid technique was positive in three cases. Such results are discussed in comparison with reports of other authors. The pertinent literature concerning clinical and pathological data is briefly reviewed. On the basis of the most recent studies on plasmacells, the histogenesis of extramedullary plasmocytoma is discussed, particularly in respect to plasmacell granulomas and multiple myeloma; the possibility that the basic cells constituting such tumors could be related to proplasmocyte is then suggested.

The ultrastructure of a dog mastocytoma examined with the electron microscope after fixation in glutaraldehyde, post-fixation in osmiumtetroxide and butyl-methyl methacrylate embedding is described. The ultrastructural characteristics with particular regard to the submicroscopic morphology of specific granules were studied in details, also with the aid of comparative observations on thick sections stained by Giemsa and toluidine blue. On the basis of their observations, the authors describe the following characteristics of neoplastic mastcells: microvilli, a well-developed Golgi region, centrioles, mithocondria, ribosomes, endoplasmic reticulum and 4 different types of granules. Other mastcells, with various degree of regressive phoenomena, had almost no microvilli, multiple interruptions of plasma membrane, mithocondrial swelling as well as vacuolar and fibrillar aspect of the cytoplasm. The morphology of different types of intracytoplasmic granules is discussed also in the light of parallel observations made by other authors. Expulsions of granules were not observed. The hypothesis of the phospholipidic nature of the lamellar component of granules is suggested.

Bone marrow from C57BL mice with myeloid leukemia induced by Graffi virus has been studied with the electron microscope by ultrathin section and negative stain techniques. Virus particles were usually found in different types of bone marrow cells as well as in extracellular spaces. However, the highest number of particles in various stages of maturation was observed in the cytoplasm of megakaryocytes. Two main types of virus particle were found: the immature Al particle and the mature C particle. They were morphologically indistinguishable from other murine leukemogenic viruses. In partially purified preparations studied by negative staining, some of the particles which were not penetrated by PTA, frequently showed a tail-like structure of variable length. In ultrathin sections, particles were found to originate by budding from the cell membranes. Budding of particles was particularly evident in megakaryocytes and especially within the granules and cytoplasmic vesicles or in connection with the platelet demarcating membranes. The findings of a high number of virus particles in all stages of maturation in megakaryocytes together with a certain degree of megakaryocytosis observed in the bone marrow suggest that this type of cell is possibly one of the main source of production of the virus. A few particles resembling morphologically mycoplasma were detected within the cytoplasm of some immature bone marrow cells.

Experiments have been performed to investigate the effects of polyinosinic-polycytidylic acid (Poly I:C) on humoral and cellular immunity in RFM/Un mice. Poly I:C, 0.1 mg i.p., administered 48 and 24 hours before 4 x 108SRBC produced a marked reduction in direct PFC/106cells and /spleen, and in the hemoagglutinin titre on the 3rd, 4th and 5th days after antigen inoculation. On the other hand, an increase in PFC and hemoagglutinin titre was observed on the 7th and 8th days. Histological examination revealed absence of germinal centers in the spleen on the 4th day. Poly I:C administered 24 and 48 hours after antigen produced an increase in direct PFC and hemoagglutinin titre on the 4th, 5th and 6th day. Histological examination disclosed evident germinal centers in the spleen on the 4th day after antigen. Poly I:C administered 5 to 1 days before antigen produced a markedly depressed direct PFC response in the groups injected 1 and 2 days before antigen. Recovery of the immune response was progressive and complete in groups injected 4 days before antigen. To study the effect of Poly I:C on secondary response to SRBC, two groups of animals injected with Poly I:C before or after antigen were reinjected with 2 x 108SRBC. Secondary response evaluated by hemoagglutinin titre at varying intervals after the immunization disclosed in both groups a much higher antibody titre than that seen in controls receiving SRBC only. Mice injected with Poly I:C 48 or 24 hours before reimmunization with 2 x 108SRBC were no different from controls on 3rd and 4th days in regard to number of indirect PFC as well as hemoagglutinin titre. Finally, mice immunized with two SRBC injections and then treated with Poly I:C on alternating days for 30 days had a much higher titre of hemoagglutinins than controls. In order to study the effect of Poly I:C on the cellular immune response, spleen cells from animals receiving Poly I:C 6–5 days before sacrifice were cultured in vitro with phytohemoagglutinin. DNA synthesis subsequent to PHA stimulation was evaluated by increase in 3HTdR incorporation. Cells from animals which had received Poly I:C demonstrated a remarkably higher 3HTdR uptake than cells from control animals. On the other hand, 5 x 106spleen cells obtained from RFM/Un mice injected with Poly I:C as above were inoculated in 1–4 day old (RFM/Un x CBA/H)F1hybrids. These were then sacrificed on day 8 and spleen indices calculated. Experimental animals disclosed GVH activity similar to that of controls (spleen index 2.3). From the results it is clear that if Poly I:C is injected before antigen the primary immune response is deppressed, whereas it is enhanced when Poly I:C is administered after antigen. On the other hand, the secondary response is generally enhanced regardless of the time of Poly I:C administration. Moreover, in Poly I:C –- treated animals there is an enhancement of PHA –- responsive cells while the GVH reactions is unchanged. As Poly I:C is capable of enhancing immune reactivity, the possibility of its use in antineoplastic chemotherapeutic protocols is suggested.

A case of malignant megakaryocytosis presenting a blood picture of acute leukemia (50%) blasts), marked hepato-splenomegaly and intense megakaryocytosis and myeloblastosis in the bone marrow, liver and spleen, is described. The authors accept megakaryocytosis as a well-defined disease entity, at least from the viewpoint of pathologic anatomy. The fairly rapid clinical course, the constant hepato-splenomegaly and the characteristic histological picture of the bone marrow, liver and spleen are the essential features necessary for a differential diagnosis from other myeloproliferative syndromes involving the megakaryocytic series.