Solitary plasmacytoma of the tonsillar site associated with actinomyces infection: the possible role of IL-6.

ExtraMedullary Plasmacytoma (EMP) is a rare plasma cell tumor. It can occur in the upper aerodigestive tract and presents as a large nodule causing local compressive symptoms. A 79-year old woman presented to Otorhinolaryngology Department with progressive hearing loss and no other symptoms. Following PET/TC examination due to the suspicion of a lymphoproliferative disease, the patient underwent tonsillectomy and the diagnosis of solitary EMP was formulated. In addition to that, the histological examination of the tonsillar tissue revealed large colonies of filamentous bacteria, showing abundant sulphur granules and Splendore-Hoeppli phenomenon; these evidences indicating the presence of a chronic Actinomyces infection. Immunohistochemical analysis demonstrated a marked IL-6 immunoreactivity of the neoplastic plasma cells. Interestingly, a marked IL-6 immunoreactivity was also found in the tissue surrounding the Actinomyces colonies. In the present study we report for the first time a solitary EMP associated with Actinomycosis. It is tempting to speculate that the unsuspected and untreated Actinomyces infection, through chronic IL-6 production, could contribute to the neoplastic transformation of plasma cells.

Plasmacytoma associated with canaliculitis.

Plasmacytomas are plasma cell neoplasms that rarely involve ocular adnexal tissues as a primary lesion or secondary manifestation of plasma cell myeloma. Only one case of plasmacytoma involving the lacrimal drainage system, to our knowledge, is described in the literature. The clinical presentation of ocular adnexal primary plasmacytoma typically relates to its mass effect. In this clinicopathologic report, we describe an unusual presentation of primary plasmacytoma of the lacrimal canaliculus as infectious canaliculitis.

Primary gastric plasmacytoma associated with Helicobacter pylori infection: a report of two cases with different prognosis.

We describe two cases of primary gastric plasmacytoma (GP) associated with Helicobacter pylori infection. Case 1 was that of a 58-year-old man with epigastric pain. H. pylori was eradicated before surgical resection was performed, and after the therapy, the tumor size was reduced. A postoperative pathological examination revealed that the tumor was in early stage and histological grade was grade 1. After 44 months of operation, the patient was in complete remission with no evidence of local relapse or progression to systemic MM. Case 2 was that of a 70-year-old woman with a history of melena. H. pylori eradication was not presented preoperatively. The resected specimen showed the tumor was in advanced stage and histological grade 3. GP eventually progressed to MM and she died of pulmonary infection. In our opinion, GP cannot be eradicated with H. pylori eradication, but disease progression can be effectively controlled to a certain extent. The prognosis of this disease is relatively fair when treated at an early stage. In addition to the treatment, the difference in prognosis could be associated with age, the stage of the tumor, and histological grade.

Gastric plasmacytoma and Helicobacter pylori infection.

A 59-year-old man with a history of melena and upper abdominal pain was referred to our hospital. An upper endoscopy was performed, and a gastric ulcer was found bordering the antrum and stomach body. Multiple biopsies from the lesion showed monoclonal plasmacytic infiltration of the mucosa, consistent with the diagnosis of plasmacytoma. Helicobacter pylori was also identified. Triple therapy failed and quadruple therapy eradicated the H. pylori, confirmed by repeated biopsies. Healing of the gastric lesion followed the treatment. Multiple biopsies from the scar and the entire stomach showed complete regression of the plasmacytoma. The association between gastric plasmacytoma and H. pylori is discussed.

Complete regression of primary gastric plasmacytoma following Helicobacter pylori eradication.

We describe the first case of a primary gastric plasmacytoma stage I completely regressed following Helicobacter pylori (H.pylori) eradication. The patient, a 61-year-old man, had a long history of chronic gastritis and gastric ulcers with recurrent gastrointestinal hemorrhage. Diagnosis of H.pylori infection was based on the positive urease breath test, the elevated titers of serum anti- H.pylori antibodies, and the detection of the bacterium in gastric mucosa biopsy specimens. Diagnosis of gastric plasmacytoma was based on the findings of histopathology, immunocytochemistry and in situ hybridization. Eradication of H.pylori with antibiotics was followed by disappearance of endoscopic and histopathologic features of the gastric tumor 3 months after the completion of the treatment. No relapse has been documented 20 months after the initial diagnosis of plasmacytoma. A possible causal relationship between the tumor and the underlying H.pylori infection is discussed.

Mott cell tumor of the stomach with Helicobacter pylori infection.

A plasma cell tumor of the stomach with unusual histology is reported. Macroscopically, the tumor formed two ulcers in the gastric body, and microscopic examination revealed proliferation of plasma cells producing immunoglobulin G kappa monotypic immunoglobulin, with metastatic infiltration in some perigastric lymph nodes. Most of these plasma cells had various-sized Russell bodies in the cytoplasm; hence the tumor may be called Mott cell tumor. The Russell bodies showed a strong affinity to concanavalin A by lectin immunohistochemistry, compared with those in reactive Mott cells. In addition, Helicobacter pylori (H. pylori) infection was proved by Gimenez stain and immunohistochemistry. The mixture of some centrocyte-like cells and presence of reactive lymph follicles with follicular colonization by tumor cells suggest that this lesion may be a variant of mucosa-associated lymphoid tissue lymphoma in association with H. pylori infection. The patient has shown no evidence of recurrence of the tumor after 11 years of follow up.

[Gastric solitary plasmacytoma associated with +Helicobacter pylori infection]. / Plasmocitoma solitario gástrico asociado a infección por Helicobacter pylori.

Solitary gastric plasmacitomas are infrequent tumors. They account for 5% of the extramedullary plasmacitomas. We report an unusual case in a 14 years old boy. The patient has had gastric symptoms for 2 years prior to an endoscopic examination. A fungating, ulcerated lesion was observed in the antrum. The biopsies showed a monoclonal, Lambda positive, diffuse, plasmocitic proliferation infiltrating the mucosa. Also a moderate number of Helicobacter pylori were identified in the gastric pits and numerous lymphoid follicules were observed in the deep portion of the mucosa. In view of the presence of HP infection the patient was treated with Orneprazole and Clarithromycin. Endoscopic examination and biopsies performed 3 and 5 months later showed a complete remission of the gastric lesion. At the time of this report the patient is in good physical condition, has recovered his weight and has grown 5 cm. Differential diagnosis with plasmo limpho in chronic gastritis and with lympheicitic lymphoma with plasmocitoid features had to be done. The macroscopic appearance of the gastric lesion, the absence of other inflammatory cells and monoclonality of the plasmocitic infiltration ruled out chronic gastritis. The negative staining for CD 20 as well as the abscence of lymphoid cells in the mucosal infiltrate give support: to the diagnosis of plasmocitoma. The close association between gastric MALT lymphoma and HP infection has been reported as well as its regression after antibiotic treatment for its erradication. In our review of the literature we failed to find any references to the association of HP with gastric plasmocitoma nor to its regression after antibiotic therapy.

Low-dose melphalan-induced shift in the production of a Th2-type cytokine to a Th1-type cytokine in mice bearing a large MOPC-315 tumor.

The current studies demonstrate that MOPC-315 tumor cells secrete large amounts of interleukin-10 (IL-10), which contributes to the inhibitory activity of MOPC-315 culture supernatants for the in vitro generation of antitumor cytotoxicity by MOPC-315-"immune" spleen cells. Moreover, addition of neutralizing monoclonal anti-IL-10 antibody to the in vitro stimulation cultures of cells from the tumor infiltrated spleens of mice bearing a large MOPC-315 tumor resulted in the generation of enhanced anti-MOPC-315 cytotoxicity. In contrast, addition of monoclonal anti-IL-10 antibody to the in vitro stimulation cultures of splenic cells from mice that are in the final stages of immune-mediated tumor eradication as a consequence of low-dose melphalan (L-phenylalanine mustard; L-PAM) therapy (and whose spleens no longer contain metastatic tumor cells) did not lead to enhancement in the in vitro generation of antitumor cytotoxicity. The cessation of IL-10 secretion as a consequence of low-dose L-PAM therapy of MOPC-315 tumor bearers was found to be accompanied by the acquisition of the ability to secrete interferon gamma (IFN gamma) by the splenic cells. In addition, by day 2 after low-dose L-PAM therapy a drastic decrease in the amount of IL-10 secreted by the s.c. tumor nodules was noted, which preceded the accumulation of tumor-infiltrating lymphocytes capable of secreting IFN gamma. Thus, low-dose L-PAM therapy of mice bearing a large MOPC-315 tumor leads to a shift in cytokine production from a Th2-type cytokine to a Th1-type cytokine, and it is conceivable that this shift in cytokine production plays an important role in the low-dose L-PAM-induced acquisition of antitumor immunity by hitherto immunosuppressed mice bearing a large MOPC-315 tumor.

Molecular requirements for rapid plasmacytoma and pre-B lymphoma induction by Abelson murine leukemia virus in myc-transgenic mice.

Mutants and fusion products of the c-abl gene were used to define some of the molecular requirements for rapid plasmacytoma (PC) and pre-B-lymphoma induction in pristane-treated N-myc transgenic BALB/c mice. A-MuLV induced PCs in 21 of 25 mice with a mean post-pristane latency period of 46 +/- 9 days, compared to 134 +/- 25 days in controls exposed to pristane alone. delta XB, a mutant of type IV c-abl with a deletion of the SH3 domain, was equally effective in inducing PCs in 7 of 7 mice with a latency period of 49 +/- 7 days, indicating that gag sequences are not required for rapid PC induction. The delta XB delta Nar mutant that carried a large C-terminal deletion in addition showed only a negligible activity, if any, suggesting that PC acceleration requires the C-terminal domain in the same way as lymphoid transformation and in contrast to fibroblast transformation. BCR-ABL fusion constructs encoding an 185-kDa protein as in acute leukemia, or a 210-kDa protein as in chronic myelocytic leukemia (CML), did not accelerate pristane-induced PC development in the N-myc transgenic mice, in contrast to their known ability to immortalize lymphoid cells in vitro. Only one of 14 non-transgenic littermates developed a pre-B lymphoma after A-MuLV infection, and none of 10 normal littermates infected with delta XB virus developed a construct-carrying tumor. This result suggests that PC acceleration is due to co-operative interaction of the N-myc transgene and activated abl. Infection of N-myc transgenic bone marrow or spleen cells with A-MuLV in vitro led to the outgrowth of pre-B lymphomas after transplantation to pristane-treated BALB/c recipients. The lymphoma-inducing activity of A-MuLV depends on its high titer, since diluted A-MuLV or the lower-titered delta XB induced only PCs under the same conditions. The v-abl, delta XB and BCR-ABL-carrying viruses generated immortalized lymphoblastoid lines in vitro, regardless of the presence of the N-myc transgene, suggesting that lymphoid transformation is a direct function of appropriate abl sequences in contrast to PC acceleration.

PANG, a gene encoding a neuronal glycoprotein, is ectopically activated by intracisternal A-type particle long terminal repeats in murine plasmacytomas.

Plasmacytomagenesis provides a murine model to decipher progressive genetic events culminating in a B-cell neoplasia. Activation of the c-myc protooncogene by chromosomal translocation is considered an initiating event. Intracisternal A-type particles (IAPs) are defective retroviral-like structures present in the endoplasmic reticulum of plasmacytomas (PCTs). IAP proviral insertions have been documented to engender negative or positive effects on the expression of nearby cellular genes. We have isolated a gene, PANG (plasmacytoma-associated neuronal glycoprotein), that is ectopically transcribed in a number of PCTs due to IAP long terminal repeat (LTR) activation. A full-length PANG cDNA was isolated from an MPC-11 plasma cell tumor cDNA library and encodes a polypeptide of about 113 kDa with six immunoglobulin C2-like and four type III fibronectin-like domains. PANG bears a striking resemblance to axonal glycoproteins TAG-1 and F11 known to function in neuronal outgrowth. An extensive survey revealed a predominant 3.6-kb PANG transcript in 60% (30 of 50) of PCTs as well as unique smaller and larger species. All other normal and transformed lymphoid and nonlymphoid cell lines and normal tissues were negative for PANG expression except for the brain, wherein unique 4.0- and 6.1-kb transcripts were detected. Reverse transcriptase PCR analysis revealed IAP LTR fusion to PANG mRNAs in five PCTs and in a neuroblastoma line. The 5' end of a mouse brain PANG cDNA was identical to the MPC-11 PANG transcript except for the precise replacement of its 5' LTR sequence.

Induction of plasmacytomas that secrete monoclonal anti-peptide antibodies by retroviral transformation.

ABL-MYC, a retrovirus that coexpresses v-abl and c-myc, was used to infect six BALB/c mice that had been immunized twice with a KLH-conjugated peptide that consisted of the 18 carboxyterminal amino acids of protein kinase C-eta (PKC-eta). All mice developed transplantable, monoclonal plasmacytomas, and five out of six plasmacytomas secreted antigen-specific antibodies, even after transplantation. All these antibodies recognized PKC-eta on Western blots of crude cell lysates and did not cross react with other isoforms of the PKC family.

Selective expression of intracisternal A-particle genes in established mouse plasmacytomas.

Mouse plasmacytomas generally express higher levels of RNA transcripts from endogenous intracisternal A-particle (IAP) proviral elements than do lipopolysaccharide-stimulated normal lymphocytes. Lymphocytes express a limited and highly characteristic set of IAP elements (lymphocyte-specific [LS] elements). In this study, we examined whether LS elements are expressed at higher levels after transformation of the cells and/or whether new IAP elements are activated. The IAP elements expressed in plasmacytoma MPC11 were characterized by sequence analysis of 22 cDNA clones. The long terminal repeats (LTRs) of the tumor cDNAs proved to be highly related in sequence. None of the clones was of the LS cDNA type. The MPC11 LTRs were five- to sixfold more active than an LS cDNA LTR when tested for promoter activity by transfection into plasmacytoma cells. The LTRs of the tumor-derived cDNAs contained a canonical ATF core sequence (ATF-PC), while the LS cDNAs contained an altered sequence (ATF-LS). An ATF-PC oligonucleotide probe detected multiple IAP transcripts on Northern (RNA) blots of RNA from several plasmacytoma but gave no reaction with RNA from stimulated B lymphocytes. In contrast, an ATF-LS probe detected higher levels of RNA in lymphocyte than in tumor RNAs. Thus, expression of IAP elements in transformed B cells is selective for a different set of regulatory sequence variants than those expressed in normal B cells. Other oligonucleotide probes representing LS- and PC-specific sequence variants detected multiple common hypomethylated IAP proviral loci in three independently derived plasmacytomas. Overall, the results show that established plasmacytomas exhibit a characteristic pattern of IAP proviral hypomethylation and regulatory sequence selection.

IgG-kappa-type plasmacytoma secreting salivary-type amylase in adult T-cell leukemia.

A IgG-kappa-type plasmacytoma secreting salivary-type amylase ectopically is reported in a patient with smouldering adult T-cell leukemia(ATL). The patient had plasmacytomas in the distal region of the right femur, the proximal region of left tibia, and the left paranasal sinus. Both his serum and urine contained high levels of amylase. The presence of IgG-kappa and S-type amylase in the plasmacytoma cells was confirmed immunocytochemically. In addition, he was also positive for the antibody against the human T-cell leukemia virus type I (HTLV-I), and had abnormal lymphocytes with convoluted nuclei (ATL cells) in the peripheral blood. The monoclonal integration of HTLV-I proviral DNA was demonstrated in the leukemic cells of the peripheral blood, but not in the plasmacytoma cells. Our case suggested that not only can HTLV-I infection play a role in the development of ATL, but may also induce a B-cell malignancy in an indirect manner, and even an ectopic amylase producing plasmacytoma.

Detection of human papillomavirus type 16 in plasma cells.

Chronic benign plasma cell tumor of the cervix, also called chronic plasma cell cervicitis, is a rare disease of unknown etiology, characterized by a heavy infiltration of plasma cells forming granulation tissue. To identify infectious agents associated with this disease, we extracted and analyzed DNA from the 17-year-old paraffin section of the original case report and from granulation tissue surgically removed from a patient at our institution with a chronic benign plasma cell tumor. The DNA from both patients was shown by a polymerase chain reaction (PCR) technique to contain a human papillomavirus 16 (HPV 16) sequence. Genomic Southern analysis of the fresh-frozen tissue confirmed the initial PCR finding. In situ hybridization further demonstrated that the HPV 16 was present in the plasma cells and not a contaminant from the surrounding epithelial tissue. The etiological role of HPV 16, an oncogenic virus associated with cervical carcinoma, in this disease is not yet clear. Our results, however, suggest that the types of cells that are infected by HPV may include cells of lymphoid origin, and that HPV may be associated with chronic benign plasma cell tumors of the cervix.

Abelson murine leukemia virus transforms preneoplastic Emu-myc transgene-carrying cells of the B-lymphocyte lineage into plasmablastic tumors.

E mu-myc transgenic mice were back-crossed to BALB/c mice up to back-cross generation 3. The offspring that included transgene-carrying and -negative mice in approximately equal proportions were randomly divided into 2 groups. Thirty-four mice (group I) were treated with pristane, followed by A-MuLV, and 40 (group II) were injected with A-MuLV alone. Altogether, 16 lymphoid tumors developed in group I and 17 in group II. Nine of the tumors in group I and 4 in group II appeared as ascitic tumors. The ascites contained lymphoblasts and 10 to 45% plasmacytoid cells. These tumors were designated as plasmablastic lymphomas (PLs). All tumors except one were transgene-positive and did not carry translocations. An exceptional tumor in group I carried a variant 6;15 translocation but not the transgene. It obviously corresponds to the regular Abelson + pristane-induced plasmacytoma. Among 11 tested PLs, 10 had a single retroviral insertion site, while one tumor showed 3. Among 18 untreated transgenic descendants (group III), chosen randomly during serial back-crosses, 15 (83%) developed lymphomas, with no sign of plasmacytoid differentiation. The incidence was comparable in all 3 groups, assuming 50% of the mice in groups I and II to be transgenic. The time distribution of tumor development was also similar. Spleen cells from transgene-carrying mice with no clinical sign of lymphoma were infected in vitro with A-MuLV and transplanted i.p. into BALB/c recipients. PLs developed in 26 of 31 pristane-treated recipients, but in only one of 18 untreated recipients. One of 6 PLs tested was monoclonal, whereas the remaining 5 were oligoclonal. They all expressed v-abl. These results show that some of the preneoplastic B-cells that expressed constitutively active myc transgene turned into plasmablasts after infection with A-MuLV. Full development of their neoplastic potential was facilitated by the presence of pristane-granuloma.

Antitumor activity of Borrelia burgdorferi cultures.

Cultures of B. burgdorferi, their supernatants as well as washed cells revealed in vitro a considerable antitumor activity against cells of Gardner lymphoma. Németh-Kellner lymphoma and LP-2 plasmacytoma. In in vivo tests an inhibition of tumor growth was evident, even if the treatment was started on day 4 after implantation of the tumor. The best results were obtained with the supernatants of the cultures.