Polypoid Carcinoma of the Oropharynx with Stromal Ossifying Myofibroblastic Proliferation: A Case Report and Literature Review

A 76-year-old man reported a worsening difficulty in swallowing, leading to the inability to eat. Physical examination and CT scan revealed a polypoid mass on the posterior oropharynx and obstructing the oropharyngeal space. Histologically, the surface was ulcerated. In the underlying necrotic rim, there was active granulation tissue, and a proliferation of voluminous, globoid elements with hyperchromatic and irregular nucleus, sometimes arranged in a alveolar aggregate. The core of the lesion contained spindle-like myoid elements in interwoven bundles, with trabeculae of osteoid matrix maturing into calcified bone. Immunohistochemistry documented positivity for cytokeratins, epithelial membrane antigen, and P63 in the globoid elements beneath the necrotic rim; strong and diffuse expression of vimentin, smooth muscle actin, and CD99 and BCL2 in the spindle elements; and complete negativity for cytokeratin 5/6, high molecular weight cytokeratin (clone 34βE12), S100, muscle-specific actin, desmin, CD117, and anaplastic lymphoma kinase. The lesion was morphologically and immunophenotypically classified as a polypoid oropharyngeal carcinoma with ossifying myofibroblastic stromal proliferation.

Morphology of Bone Marrow Plasma Cells (BMPC) and Its Relationship with Interphase Cytogenetics and Prognosis in Multiple Myeloma (MM).

Abstract 1822 Poster Board I-848 Background BMPC number is important for diagnostic purposes in monoclonal gammopathies whereas BMPC morphology may be used as a prognostic factor in MM. So far, presence of plasmablasts or of BMPC displaying irregular nuclear outline have been related to adverse prognosis in MM. Interphase FISH demonstrates several cytogenetic changes (CG) in MM, and 17p deletion (del17p) and t(4;14) translocation have been recently shown as both major adverse prognostic factors. Up to 70% pts, however, lack both these CG changes, and prognostic parameters, easy-to-perform in routine practice, are needed for these patients. Our aim in this study was to ascertain whether BMPC morphology displayed prognosis in pts who did not demonstrate both adverse CG changes. Methods. We performed a retrospective analysis of BMPC morphology from 245 patients with MM, uniformly treated within the IFM 99 trials based on presence or absence of high serum beta-2 microglobulin level and 13q- deletion, including IFM 99-02, 99-03, and 99-04. Interphase FISH was performed using previously published methods on sorted BMPC to look for del13q, t(11;14), del17p, and t(4;14) (one to four sets of probes tested in each pt, according to the number of PC sorted in each instance). BM smears were analyzed by at least two out of a group of five morphologists (from different University centers): in each case 100 BMPC were observed, analyzed, and computerized. Comparison between results from observers was performed next: in all instances, if discordance occurred, computerized images were observed by all five morphologists (meeting sessions and Email sessions) leading to consensus. Results Median age was 55, and 38% of patients had ISS 2 and 3 in the overall cohort. 72.3%, 6.8% and 20.9% patients came from the 99-02, 99-03, and 99-04 trials, respectively. Pts were classified according to five morphological subgroups: Mature (>66% of PC displaying mature morphology) [n=74 (30.2%)], Small Plasmacytic (>15% of PC displaying mature morphology but high N/C ratio) [n=14 pts (5.7%)], Plasmablastic (>=1% plasmablasts) [n=48 (19.6%)], Irregular Nucleus (>5% PC displaying irregular nuclear outline, PCIN) [n=32 pts (30.2%)], Activated (one nucleolus in >33% PC and/or immature chromatin network in >10% PC) [n=76 (31%)]. Del13 was found in 125 pts (51%), t(11;14) in 43pts (17.6%), del17p in 16 pts (7.0%), and t(4;14) in 52 pts (21.2%). Del17p and t(4;14) were both absent in 181 pts (73.9%). This group had no clinic-biological difference with the overall population of the trials. The median follow up was 49 months (+/-se 0.74). Median Progression Free Survival (PFS) and Overall Survival (OS) were lower in the adverse CG group [displaying either del17p or t(4;14)] as compared to other pts: 21 vs 43 months (p<0.0001) and 42 months vs median not reached (p<0.0001), respectively. 33 pts (51.5%) with adverse CG changes displayed also adverse morphology [either plasmablastic or irregular nucleus]. Combination of adverse CG and adverse morphology led to dismal prognosis: median PFS were 20 months for pts with both adverse CG and morphology prognostic factors, and 36 months for pts with adverse morphology solely (p=0.0001), and median OS were 37 months and not reached (p=0.002), respectively. For pts without adverse CG changes, presence of plasmablasts or/and of irregular nucleus was related to adverse prognosis [median PFS and OS for both subgroups were 36 months (p=0.034) and 49 months (p=0.039)]. In contrast, mature and activated MM groups both showed better prognosis (median PFS were 45 and 49 months and median OS were not reached). Small plasmacytic MM group was peculiar, displaying t(11;14) in 85% cases but almost never del17p or t(4;14) (1.6% cases). This subgroup demonstrated here lower PFS and OS [34 months and 45 months, respectively] as compared to the Mature group, but also as compared to the whole t(11;14) population tested [43 months and median not reached, respectively]. Conclusion Adverse morphological changes and adverse CG changes together lead to dismal prognosis. For pts who do not display del17p and t(4;14) we show here that plasmablasts and irregular nucleus are morphological changes which remain of adverse prognosis. T(11;14) is associated with high number of small PC and is related to intermediate prognosis, whereas quite good prognosis is associated with mature or activated BMPC. Modulation of therapy according to CG but also to BMPC morphology is stressed. Disclosures No relevant conflicts of interest to declare.

Transgenic Mice for MTCP1 Develop T-Cell Prolymphocytic Leukemia

T-cell prolymphocytic leukemia (T-PLL) is a rare form of mature T-cell leukemia associated with chromosomal rearrangements implicatingMTCP1 or TCL1 genes. These genes encode two homologous proteins, p13MTCP1 and p14TCL1, which share no similarity with other known protein. To determine the oncogenic role of MTCP1, mice transgenic for MTCP1under the control of CD2 regulatory regions (CD2-p13 mice) were generated. No abnormality was detected during the first year after birth. A late effect of the transgene was searched for in a cohort of 48 CD2-p13 mice aged 15 to 20 months, issued from 3 independent founders. Lymphoid hemopathies, occurring in the three transgenic lines, were characterized by lymphoid cells with an irregular nucleus, a unique and prominent nucleolus, condensed chromatin, a basophilic cytoplasm devoid of granules, and an immunophenotype of mature T cells. The molecular characterization of Tcrb rearrangements demonstrated the monoclonal origin of these populations. Histopathological analysis of the cohort demonstrated early splenic and hepatic infiltrations, whereas lymphocytosis and medullar infiltrations were found infrequently. The engraftment of these proliferations in H2-matched animals demonstrated their malignant nature. Cumulative incidence of the disease at 20 months was 100%, 50%, and 21% in F3, F4, and F7 lines, respectively, and null in the control group. The level of expression of the transgene, as estimated by Western blotting in the transgenic lines correlated with the tumoral incidence, with the highest expression of p13MTCP1 being found in F3 mice. CD2-p13 transgenic mice developed an hemopathy similar to human T-PLL. These data demonstrate that p13MTCP1 is an oncoprotein and that CD2-p13 transgenic mice represent the first animal model for mature T-PLL.

Transgenic Mice for MTCP1 Develop T-Cell Prolymphocytic Leukemia

T-cell prolymphocytic leukemia (T-PLL) is a rare form of mature T-cell leukemia associated with chromosomal rearrangements implicatingMTCP1 or TCL1 genes. These genes encode two homologous proteins, p13MTCP1 and p14TCL1, which share no similarity with other known protein. To determine the oncogenic role of MTCP1, mice transgenic for MTCP1under the control of CD2 regulatory regions (CD2-p13 mice) were generated. No abnormality was detected during the first year after birth. A late effect of the transgene was searched for in a cohort of 48 CD2-p13 mice aged 15 to 20 months, issued from 3 independent founders. Lymphoid hemopathies, occurring in the three transgenic lines, were characterized by lymphoid cells with an irregular nucleus, a unique and prominent nucleolus, condensed chromatin, a basophilic cytoplasm devoid of granules, and an immunophenotype of mature T cells. The molecular characterization of Tcrb rearrangements demonstrated the monoclonal origin of these populations. Histopathological analysis of the cohort demonstrated early splenic and hepatic infiltrations, whereas lymphocytosis and medullar infiltrations were found infrequently. The engraftment of these proliferations in H2-matched animals demonstrated their malignant nature. Cumulative incidence of the disease at 20 months was 100%, 50%, and 21% in F3, F4, and F7 lines, respectively, and null in the control group. The level of expression of the transgene, as estimated by Western blotting in the transgenic lines correlated with the tumoral incidence, with the highest expression of p13MTCP1 being found in F3 mice. CD2-p13 transgenic mice developed an hemopathy similar to human T-PLL. These data demonstrate that p13MTCP1 is an oncoprotein and that CD2-p13 transgenic mice represent the first animal model for mature T-PLL.

SOME LIGHT- AND ELECTRON-MICROSCOPICAL OBSERVATIONS ON THE PARS TUBERALIS OF THE PITUITARY GLAND OF THE RABBIT

SUMMARY The cytological appearance of the pars tuberalis both at the light- and the electron-microscopical levels is described. Two main types of cell, one, which is designated the tuberalis cell, having a rounded contour, pale cytoplasm with a few small secretory granules of about 100 nm in diameter, many polyribosomes and a relatively large ovoid nucleus; and the other, the interstitial cell, with long processes often encircling tuberalis cells, an irregular nucleus and cytoplasm with abundant microfilaments about 10 nm in diameter were seen. Beaded nerve fibres and neurosecretory material were demonstrated in the pars tuberalis with chrome alum—haematoxylin, a finding confirmed at the electron-microscopical level where nerve fibres which appeared to be making contact with tuberalis cells and containing numerous microvesicles of about 50 nm in diameter were observed.

Muscle proteins in the chick myotome examined by the immunofluorescent method

In previous studies on the development of the somite (Langman & Nelson, 1968), the majority of the cells of the myotome appeared to arise from the dermatome and not, as previously suggested, from the cells of the so-called dorso-medial somite lip (Williams, 1910; Hamilton, 1952; Boyd, 1960). Once the myotome cells, characterized by a pale, round to irregular, nucleus and darkly stained nucleolus, are formed, they fail to synthesize DNA. During subsequent development, the myotome appears to extend in ventro-lateral direction by the addition of new cells originating primarily from the dermatome. After the dermatome has lost its epithelial structure, the myotome, in transverse section, consists of a tissue band with an abundance of cytoplasm and a large number of round to spindle-shaped nuclei. Though DNA synthesis was rarely observed among the cells of the extended myotome, considerable proliferative activity was observed in the adjacent tissues.