Clinicopathologic predictors of survival in buccal squamous cell carcinoma.

BACKGROUND: Buccal squamous cell carcinoma (SCC) is a locoregionally aggressive malignancy, representing a small subset of oral cancers in North America. We investigated the prognostic value of several clinicopathologic factors in a cohort of patients diagnosed with buccal SCC. METHODS: Between years 1992 and 2017, 52 patients were diagnosed with conventional buccal SCC. Archival surgical pathology material was retrospectively reviewed for reportable findings according to the latest reporting guidelines published by the College of American Pathologists. Clinical data were obtained through chart review. RESULTS: The majority of patients were of older age, current or past smokers, and without specific gender predilection. Most presented at a clinically advanced stage and were treated with surgery alone, or surgery followed by adjuvant radiotherapy. The tumor recurred in about 40% of patients, and almost half of the patients died from the disease by the end of the follow-up period. The worst pattern of invasion (WPOI) was associated with greater depth of invasion (DOI) (P = .031) and perineural invasion (P < .001). In univariate analyses, older age (P = .004), positive nodal status (P = .047), lymphovascular invasion (P = .012), perineural invasion (P = .05), and WPOI-5 (P = .015) were adverse predictors of 5-year overall survival (OS). In multivariate analysis, older age (P = .011), WPOI-5 (P < .001), and perineural invasion (P = .001) remained statistically significant independent prognosticators of worse 5-year OS. CONCLUSIONS: Older age, WPOI-5, and perineural invasion are significant prognosticators of worse OS. WPOI is associated with DOI, a finding which may have important implications for the pathogenesis and biologic behavior of the disease.

A recurrent case of central odontogenic fibroma in maxilla showing root resorption: a case report / Fibroma odontogênico central: relato de caso recorrente e localmente agressivo na maxila

Objective: The aim of this report is present an aggressive recurrent case of central odontogenic fibroma (COF) with tooth resorption in anterior maxilla, and discuss both events based on literature. Case description: A 29-year-old woman was referred for examination of a non-swelling intraosseous lesion detected by routine radiographic exams for orthodontic planning. Panoramic exam revealed a well-defined multiloculated radiolucency in the right anterior maxilla. Periapical radiography highlighted dental resorption of canine and first premolar. After the incisional biopsy the COF diagnosis was confirmed. Tumor was removed by enucleation. Recurrence was detected three years later and the lesion was removed together with involved teeth. No indication of recurrence has been observed in the past eight years. Conclusion: COF is a benign tumor and can be aggressive. Recurrence and root resorption simultaneously are rare features reported in literature. The treatment must include tooth removal and curettage. Prognosis is good and follow-up is important.

Objetivo: O objetivo deste relato é apresentar um caso clínico de fibroma odontogênico central (FOC) recorrente e com reabsorção dental em região anterior de maxila, e discutir estes dois eventos baseados na literatura. Descrição do Caso: Paciente do sexo feminino, 29 anos, foi encaminhada para avaliação de lesão intraóssea não-expansiva, detectada por exames radiográficos solicitados para planejamento ortodôntico. Exames radiográficos mostraram uma área radiolúcida multiloculada bem delimitada com reabsorção radicular de canino e primeiro pré-molar direito. Após biópsia incisional e exame histopatológico, a lesão foi diagnosticada como fibroma odontogênico central. O tumor foi enucleado e três anos depois, detectou-se recorrência. A lesão recorrente foi removida junto aos dentes adjacentes. Nenhuma recorrência foi observada nos últimos oito anos de acompanhamento. Conclusão: FOC é um tumor benigno que pode apresentar comportamento agressivo. Recorrência e reabsorção radicular simultâneas são características raramente relatadas na literatura. O tratamento deve incluir exodontia e curetagem do sítio cirúrgico. O acompanhamento é importante, embora seja uma lesão de prognóstico favorável.

Expression of hypoxia-induced factor-1 alpha in early-stage and in metastatic oral squamous cell carcinoma.

To investigate hypoxia-induced factor-1 alpha expression in distinct oral squamous cell carcinoma subtypes and topographies and correlate with clinicopathological data. Hypoxia-induced factor-1 alpha expression was assessed by immunohistochemistry in 93 cases of OSCC. Clinical and histopathological data were reviewed from medical records. Hypoxia-induced factor-1 alpha status was distinct according to tumor location, subtype and topography affect. In superficial oral squamous cell carcinomas, most tumor cells overexpressed hypoxia-induced factor-1 alpha, whereas hypoxia-induced factor-1 alpha was restricted to the intratumoral region in conventional squamous cell carcinomas. All basaloid squamous cell carcinomas exhibited downregulation of hypoxia-induced factor-1 alpha. Interestingly, metastatic lymph nodes (91.7%, p = 0.001) and the intratumoral regions of corresponding primary tumors (58.3%, p = 0.142) showed hypoxia-induced factor-1 alpha-positive tumor cells. Overall survival was poor in patients with metastatic lymph nodes. Hypoxia-induced factor-1 alpha has distinct expression patterns in different oral squamous cell carcinoma subtypes and topographies, suggesting that low oxygen tension promotes the growth pattern of superficial and conventional squamous cell carcinoma, but not basaloid squamous cell carcinoma. Indeed, a hypoxic environment may facilitate regional metastasis, making it a useful diagnostic and prognostic marker in primary tumors.

Conversion of Prostate Adenocarcinoma to Small Cell Carcinoma-Like by Reprogramming.

The lineage relationship between prostate adenocarcinoma and small cell carcinoma was studied by using the LuCaP family of xenografts established from primary neoplasm to metastasis. Expression of four stem cell transcription factor (TF) genes, LIN28A, NANOG, POU5F1, SOX2, were analyzed in the LuCaP lines. These genes, when force expressed in differentiated cells, can reprogram the recipients into stem-like induced pluripotent stem (iPS) cells. Most LuCaP lines expressed POU5F1, while LuCaP 145.1, representative of small cell carcinoma, expressed all four. Through transcriptome database query, many small cell carcinoma genes were also found in stem cells. To test the hypothesis that prostate cancer progression from "differentiated" adenocarcinoma to "undifferentiated" small cell carcinoma could involve re-expression of stem cell genes, the four TF genes were transduced via lentiviral vectors into five adenocarcinoma LuCaP lines-70CR, 73CR, 86.2, 92, 105CR-as done in iPS cell reprogramming. The resultant cells from these five transductions displayed a morphology of small size and dark appearing unlike the parentals. Transcriptome analysis of LuCaP 70CR* ("*" to denote transfected progeny) revealed a unique gene expression close to that of LuCaP 145.1. In a prostate principal components analysis space based on cell-type transcriptomes, the different LuCaP transcriptome datapoints were aligned to suggest a possible ordered sequence of expression changes from the differentiated luminal-like adenocarcinoma cell types to the less differentiated, more stem-like small cell carcinoma types, and LuCaP 70CR*. Prostate cancer progression can thus be molecularly characterized by loss of differentiation with re-expression of stem cell genes. J. Cell. Physiol. 231: 2040-2047, 2016. © 2016 Wiley Periodicals, Inc.

Risk factors for locoregional relapse after transoral robotic surgery for human papillomavirus-related oropharyngeal squamous cell carcinoma.

BACKGROUND: Factors predicting locoregional relapse after surgery for oropharyngeal squamous cell carcinoma (SCC) were identified in the pre-human papillomavirus (HPV) era. We examined whether traditional indications for adjuvant radiotherapy (RT) or adjuvant chemoradiotherapy (CRT) still correlate with locoregional relapse in HPV-positive patients after transoral robotic surgery (TORS). METHODS: Retrospective review of oropharyngeal SCC cases identified patients with HPV-positive tumors who did not receive adjuvant therapy after TORS despite intermediate or high-risk features. RESULTS: Median follow-up was 26.7 months (range, 4.9-73.1 months). Five of 25 eligible patients (20%) relapsed at a median 4.8 months (range, 3.2-7.8 months). Two of 18 (11%) intermediate and 3 of 7 (43%) high-risk patients relapsed. Kaplan-Meier 2-year locoregional relapse-free survival estimates for intermediate and high-risk patients were 88% and 57% (p = .078), respectively. CONCLUSION: Traditional indications for adjuvant RT or CRT were associated with high risk of locoregional relapse in HPV-positive patients treated with TORS alone. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1674-E1679, 2016.

Reprogramming of prostate cancer cells--technical challenges.

Prostate cancer progression is characterized by tumor dedifferentiation. Cancer cells of less differentiated tumors have a gene expression/transcriptome more similar to that of stem cells. In dedifferentiation, cancer cells may follow a specific program of gene expression changes to a stem-like state. In order to treat cancer effectively, the stem-like cancer cells and cancer differentiation pathway need to be identified and studied. Due to the very low abundance of stem-like cancer cells, their isolation from fresh human tumors is technically challenging. Induced pluripotent stem cell technology can reprogram differentiated cells into stem-like, and this may be a tool to generate sufficient stem-like cancer cells.

Angiotensin II type 1 receptor blockade restores angiotensin-(1-7)-induced coronary vasodilation in hypertrophic rat hearts.

The aim of the present study was to investigate the coronary effects of Ang-(1-7) [angiotensin-(1-7)] in hypertrophic rat hearts. Heart hypertrophy was induced by abdominal aorta CoA (coarctation). Ang-(1-7) and AVE 0991, a non-peptide Mas-receptor agonist, at picomolar concentration, induced a significant vasodilation in hearts from sham-operated rats. These effects were blocked by the Mas receptor antagonist A-779. Pre-treatment with L-NAME (N(G)-nitro-L-arginine methyl ester) or ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinozalin-1-one) [NOS (NO synthase) and soluble guanylate cyclase inhibitors respectively] also abolished the effect of Ang-(1-7) in control hearts. The coronary vasodilation produced by Ang-(1-7) and AVE 0991 was completely blunted in hypertrophic hearts. Chronic oral administration of losartan in CoA rats restored the coronary vasodilation effect of Ang-(1-7). This effect was blocked by A-779 and AT2 receptor (angiotensin II type 2 receptor) antagonist PD123319. Acute pre-incubation with losartan also restored the Ang-(1-7)-induced, but not BK (bradykinin)-induced, coronary vasodilation in hypertrophic hearts. This effect was inhibited by A-779, PD123319 and L-NAME. Chronic treatment with losartan did not change the protein expression of Mas and AT2 receptor and ACE (angiotensin-converting enzyme) and ACE2 in coronary arteries from CoA rats, but induced a slight increase in AT2 receptor in aorta of these animals. Ang-(1-7)-induced relaxation in aortas from sham-operated rats was absent in aortas from CoA rats. In vitro pre-treatment with losartan restored the Ang-(1-7)-induced relaxation in aortic rings of CoA rats, which was blocked by the Mas antagonist A-779 and L-NAME. These data demonstrate that Mas is strongly involved in coronary vasodilation and that AT1 receptor (angiotensin II type 1 receptor) blockade potentiates the vasodilatory effects of Ang-(1-7) in the coronary beds of pressure-overloaded rat hearts through NO-related AT2- and Mas-receptor-dependent mechanisms. These data suggest the association of Ang-(1-7) and AT1 receptor antagonists as a potential therapeutic avenue for coronary artery diseases.

Reprogramming of prostate cancer-associated stromal cells to embryonic stem-like.

BACKGROUND: CD90(+) prostate cancer-associated (CP) stromal cells represent a diseased cell type found only in tumor tissue. They differ from their normal counterpart in gene expression and inductive signaling. Genetic reprogramming by induced pluripotent stem (iPS) cell technology can effectively change adult cells into stem-like cells through wholesale alteration of the gene expression program. This technology might be used to 'erase' the abnormal gene expression of diseased cells. The resultant iPS cells would no longer express the disease phenotype, and behave like stem cells. METHODS: CP stromal cells, isolated from tumor tissue of a surgically resected prostate by anti-CD90-mediated sorting and cultured in vitro, were transfected with in vitro packaged lentiviral expression vectors containing stem cell transcription factor genes POU5F1, LIN28, NANOG, and SOX2. RESULTS: Alkaline phosphatase-positive iPS cells were obtained in about 3 weeks post-transfection at a frequency of 10(-4) . Their colony morphology was indistinguishable from that of human embryonic stem (ES) cells. Transcriptome analysis showed a virtually complete match in gene expression between the iPS and ES cells. CONCLUSIONS: Genes of CP stromal cells could be fully inactivated by genetic reprogramming. As a consequence, the disease phenotype was 'cured'.

Mesenchymal chondrosarcoma in the mandible: report of a case with cytological findings.

Mesenchymal chondrosarcoma is an infrequent malignancy of bone and soft tissue, characterized by its peculiar bimorphic histological pattern. The use of fine-needle aspiration (FNA) in the diagnosis of bone tumors is controversial. A 31-year-old woman presented with a mandibular lesion detected on routine examination for orthodontic treatment. Radiography revealed an ill-defined mixed radiolucency in the premolar region of the right mandible with invasive characteristics such as root resorption and widening of the periodontal ligament space of neighboring teeth. Blood clots obtained at FNA were fixed in formalin and exhibited spindle cells surrounding islands of pleomorphic chondroblasts against a bloody background. Histopathologically, clusters of spindle cells juxtaposed with mesenchymal tissue were detected, with a large hemangiopericytomatous component. In the present case, cytological findings combined with clinical and radiological data provided valuable information in establishing the diagnosis of malignancy and in planning further procedures and treatment.

Lineage relationship of prostate cancer cell types based on gene expression.

BACKGROUND: Prostate tumor heterogeneity is a major factor in disease management. Heterogeneity could be due to multiple cancer cell types with distinct gene expression. Of clinical importance is the so-called cancer stem cell type. Cell type-specific transcriptomes are used to examine lineage relationship among cancer cell types and their expression similarity to normal cell types including stem/progenitor cells. METHODS: Transcriptomes were determined by Affymetrix DNA array analysis for the following cell types. Putative prostate progenitor cell populations were characterized and isolated by expression of the membrane transporter ABCG2. Stem cells were represented by embryonic stem and embryonal carcinoma cells. The cancer cell types were Gleason pattern 3 (glandular histomorphology) and pattern 4 (aglandular) sorted from primary tumors, cultured prostate cancer cell lines originally established from metastatic lesions, xenografts LuCaP 35 (adenocarcinoma phenotype) and LuCaP 49 (neuroendocrine/small cell carcinoma) grown in mice. No detectable gene expression differences were detected among serial passages of the LuCaP xenografts. RESULTS: Based on transcriptomes, the different cancer cell types could be clustered into a luminal-like grouping and a non-luminal-like (also not basal-like) grouping. The non-luminal-like types showed expression more similar to that of stem/progenitor cells than the luminal-like types. However, none showed expression of stem cell genes known to maintain stemness. CONCLUSIONS: Non-luminal-like types are all representatives of aggressive disease, and this could be attributed to the similarity in overall gene expression to stem and progenitor cell types.

Differential Inductive Signaling of CD90 Prostate Cancer-Associated Fibroblasts Compared to Normal Tissue Stromal Mesenchyme Cells.

UNLABELLED: Prostate carcinomas are surrounded by a layer of stromal fibroblastic cells that are characterized by increased expression of CD90. These CD90(+) cancer-associated stromal fibroblastic cells differ in gene expression from their normal counterpart, CD49a(+)CD90(lo) stromal smooth muscle cells; and were postulated to represent a less differentiated cell type with altered inductive properties. CD90(+) stromal cells were isolated from tumor tissue specimens and co-cultured with the pluripotent embryonal carcinoma cell line NCCIT in order to elucidate the impact of tumor-associated stroma on stem cells, and the 'cancer stem cell.' Transcriptome analysis identified a notable decreased induction of smooth muscle and prostate stromal genes such as PENK, BMP2 and ChGn compared to previously determined NCCIT response to normal prostate stromal cell induction. CD90(+) stromal cell secreted factors induced an increased expression of CD90 and differential induction of genes involved in extracellular matrix remodeling and the RECK pathway in NCCIT. These results suggest that, compared to normal tissue stromal cells, signaling from cancer-associated stromal cells has a markedly different effect on stem cells as represented by NCCIT. Given that stromal cells are important in directing organ-specific differentiation, stromal cells in tumors appear to be defective in this function, which may contribute to abnormal differentiation found in diseases such as cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12307-010-0061-4) contains supplementary material, which is available to authorized users.

Embryonal carcinoma cell induction of miRNA and mRNA changes in co-cultured prostate stromal fibromuscular cells.

The prostate stromal mesenchyme controls organ-specific development. In cancer, the stromal compartment shows altered gene expression compared to non-cancer. The lineage relationship between cancer-associated stromal cells and normal tissue stromal cells is not known. Nor is the cause underlying the expression difference. Previously, the embryonal carcinoma (EC) cell line, NCCIT, was used by us to study the stromal induction property. In the current study, stromal cells from non-cancer (NP) and cancer (CP) were isolated from tissue specimens and co-cultured with NCCIT cells in a trans-well format to preclude heterotypic cell contact. After 3 days, the stromal cells were analyzed by gene arrays for microRNA (miRNA) and mRNA expression. In co-culture, NCCIT cells were found to alter the miRNA and mRNA expression of NP stromal cells to one like that of CP stromal cells. In contrast, NCCIT had no significant effect on the gene expression of CP stromal cells. We conclude that the gene expression changes in stromal cells can be induced by diffusible factors synthesized by EC cells, and suggest that cancer-associated stromal cells represent a more primitive or less differentiated stromal cell type.

Periodontal disease and oral hygiene benefits in HIV seropositiveand AIDS patients

Objectives: The frequency of gingival and periodontal disease in HIV-seropositive and AIDS patients was investigatedin order to evaluate the oral hygiene benefits of using mechanical therapy. Study design: thirty-twoconsenting HIV-positive patients were examined. Their gingival and periodontal status were evaluated using theGingival Index and the Simplified Oral Hygiene Index. The data were assessed at baseline, after three months andafter six months. Subjects received mechanical therapy, which included calculus removal, scaling and root planning,tooth polishing and oral hygiene instructions. The maintenance of oral hygiene was performed weekly. HIVstaging and CD4 counts were also investigated. Results: At the baseline, gingival and periodontal disease waspresent in 71.9% of all subjects. Chronic gingivitis (43.8%) was the most frequent in all subjects. A clear improvementin gingival health was registered in 78.2% of subjects after six months of mechanical therapy. No associationwas registered between CD4 count and gingival/periodontal status or attachment loss with HIV staging. Conclusions:Chronic gingivitis was the most frequent disease in HIV infected and AIDS patients. Oral hygiene usingmechanical therapy improves the gingival condition, suggesting that it is an important step in the maintenance ofperiodontal health (AU)

Periodontal disease and oral hygiene benefits in HIV seropositive and AIDS patients.

OBJECTIVES: The frequency of gingival and periodontal disease in HIV-seropositive and AIDS patients was investigated in order to evaluate the oral hygiene benefits of using mechanical therapy. STUDY DESIGN: thirty-two consenting HIV-positive patients were examined. Their gingival and periodontal status were evaluated using the Gingival Index and the Simplified Oral Hygiene Index. The data were assessed at baseline, after three months and after six months. Subjects received mechanical therapy, which included calculus removal, scaling and root planning, tooth polishing and oral hygiene instructions. The maintenance of oral hygiene was performed weekly. HIV staging and CD4 counts were also investigated. RESULTS: At the baseline, gingival and periodontal disease was present in 71.9% of all subjects. Chronic gingivitis (43.8%) was the most frequent in all subjects. A clear improvement in gingival health was registered in 78.2% of subjects after six months of mechanical therapy. No association was registered between CD4 count and gingival/periodontal status or attachment loss with HIV staging. CONCLUSIONS: Chronic gingivitis was the most frequent disease in HIV infected and AIDS patients. Oral hygiene using mechanical therapy improves the gingival condition, suggesting that it is an important step in the maintenance of periodontal health.

Stromal-epithelial interactions in early neoplasia.

In prostate tumors, both the epithelial and stromal mesenchyme compartments show gene expression changes from their respective normal counterpart. In fact, there are more such changes in the stroma than the epithelium. These include down-regulated expression of genes involved in smooth muscle cell differentiation and those differentially expressed between prostate and bladder, i.e., organ-restricted. In development, the stromal cell type mediates tissue formation from differentiation of stem or progenitor cells. Diseases like cancer may arise as a result of defective stromal signaling. Stromal signaling can be demonstrated by co-culture of stromal cells and embryonal carcinoma NCCIT cells used as a stem cell substitute. In co-culture, stromal cells induce NCCIT cells through diffusible molecules to lose stem cell gene expression, gain expression of prostate genes, alter cytomorphology, and lower proliferation. This NCCIT response is varied as co-cultured bladder stromal cells induce a different gene expression. At the same time, NCCIT factors also affect gene expression of co-cultured stromal cells. NCCIT induces normal prostate tissue (NP) stromal cells to become more like cancer-associated (CP) stromal cells in both mRNA and microRNA expression. In contrast, NCCIT shows minimal effect on CP stromal cells. CP stromal cells may represent a less differentiated state in the prostate stromal cell lineage.

Clonal cytogenetic abnormalities in Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a rare histiocytic disorder of unknown etiology that involves predominantly bone and viscera. Whether ECD represents a reactive or neoplastic process has been debated since its initial description. Herein, we report for the first time the cytogenetic findings of a case of ECD diagnosed at Mayo Clinic Rochester. The tumor occurred in the right tibia of a 35-year-old man and showed the balanced chromosomal translocation t(12;15;20)(q11;q24;p13.3), among other numeric chromosomal abnormalities. The lesion was positive for CD68 and negative for CD1a and S100. These findings support the idea that some cases of ECD are clonal neoplastic disorders of putative histiocytic differentiation. However, additional studies are warranted to confirm whether the chromosomal abnormalities found in this case represent recurrent cytogenetic events.

Heterotopic ossification in the anterior maxilla: a case report and review of the literature.

A 13-year-old boy had complained of an asymptomatic swelling in the anterior maxilla for approximately 4 years. The patient reported no local trauma. The intra-oral examination revealed an exophytic lesion in the incisive papilla between the maxillary central and lateral incisor teeth. The radiographies detected no significant findings. Histopathologically, the lesion showed a dense fibrous tissue above the overlying mucosa. Bone ossification lay beneath a partially hypertrophic cartilage showing occasionally pleomorphic chondrocytes. Because of its microscopic aspects, heterotopic ossification may be mistaken for chondrosarcoma or other conditions involving periosteum, such as parosteal osteosarcoma. A case of heterotopic ossification in the anterior maxilla is presented, and clinicopathologic similarities with other osteochondromatous lesions are discussed.

Myeloma of the jaw bones: a clinicopathologic study of 33 cases.

BACKGROUND: A clinicopathologic study of 33 cases of plasma cell neoplasm of the jaw bones was performed. METHODS: The Mayo Clinic's pathology files through 1995 were reviewed for cases of plasma cell neoplasia involving the jaw bones. Clinical data, radiologic features, and follow-up data were obtained from the hospitals of origin, referring physicians, and Mayo Clinic files. The histopathologic features of the 33 tumors were studied. RESULTS: There were 21 (64%) male and 12 (36%) female patients, ranging in age from 25 to 81 years (mean, 57.7 years). Twenty-one tumors (64%) were classified as solitary plasmacytoma of bone (SPB) and 12 (36%) as multiple myeloma (MM). Among the SPB cases, 15 (71%) involved the maxilla, and 14 patients were men, with a mean age of 57.1 years. Abnormal serum protein was found in 22% of patients, and in nine patients (43%) the SPB converted to MM after a median of 20.7 months. Among the MM cases, seven (58%) affected the maxilla, seven patients were men with mean age of 58.3 years, and abnormal serum protein and Bence-Jones protein were found in 42% and 73% of the patients, respectively. Anaplastic histology was identified in seven (33%) SPB and six (50%) MM tumors, and amyloid was present in eight (38%) SPB and three (25%) MM tumors. Twelve (57%) SPB patients died of the disease after a median disease-free survival of 6.75 years, and the overall and disease-free survival rates at 5 and 10 years were 52%, 33%, 33%, and 24%, respectively. All MM patients died of the disease after a median survival of 17.6 months, and the 5-year and 10-year survival rates were 8% and zero. Eighty-six percent of the SPB patients with anaplastic histologic findings died of the disease (average survival, 3.8 years), whereas only 43% of those with classic histologic findings died of the disease (average survival, 11.75 years). Among MM patients, anaplastic histologic findings were associated with a 9-month average survival (26-month average survival for MM patients with classic histologic findings). CONCLUSIONS: SPB patients seem to have a better prognosis than MM patients, and 43% of SPB tumors convert to MM after an average of 20.7 months. Anaplastic histologic findings seem to be associated with lower survival rates and periods for SPB patients and lower survival periods for MM patients.