Diffuse low-grade oligodendrogliomas extend beyond MRI-defined abnormalities.

BACKGROUND: Imaging determinations of the spatial extent of diffuse low-grade gliomas (DLGGs) are of paramount importance in evaluating the risk-to-benefit ratio of surgical resection. However, it is not clear how accurately preoperative conventional MRI can delineate DLGGs. METHODS: We report a retrospective histologic and imaging correlation study in 16 adult patients who underwent serial stereotactic biopsies for the diagnosis of untreated supratentorial well-defined and non-contrast-enhanced DLGG, in whom biopsy samples were taken within and beyond (OutBSs) MRI-defined abnormalities. RESULTS: Thirty-seven OutBSs that extended from 10 to 26 mm beyond MRI-defined abnormalities were studied. Immunostaining revealed MIB-1-positive cells (i.e., cycling cells) in all but 2 of the OutBSs. None of the MIB-1-positive cells coexpressed glial fibrillary acidic protein, and all of them coexpressed OLIG2. MIB-1-positive cells were cycling isolated tumor cells, because 1) their morphologic characteristics reflected those of tumor cells, 2) the number of MIB-1-positive cells per square centimeter was significantly higher than that of controls, 3) the number of MIB-1-positive cells per square centimeter was positively correlated with the tumor growth fraction (p = 0.012), and 4) the number of MIB-1-positive cells per square centimeter in OutBSs decreased with distance from the tumor (p = 0.003). CONCLUSIONS: This study demonstrates, using a multiscale correlative approach, that conventional MRI underestimates the actual spatial extent of diffuse low-grade gliomas (DLGGs), even when they are well delineated. These results suggest that an extended resection of a margin beyond MRI-defined abnormalities, whenever feasible in noneloquent brain areas, might improve the outcome of DLGGs.

Modulation of ER phosphorylation on serine 118 by endocrine therapy: a new surrogate marker for efficacy.

BACKGROUND: Phosphorylation of serine 118 (ser118) has been reported to be involved in the activation of estrogen receptor (ER). In the present study, we evaluated whether endocrine therapy modulated ER phosphorylation on ser118. PATIENTS AND METHODS: We carried out a tissue microarray that included 80 primary breast tumors obtained before the administration of endocrine therapy. A second tissue microarray included 52 tumors obtained after endocrine therapy from the same patients. Immunostainings were carried out for ER, Pser118ER, Her2, insulin growth factor receptor (IGFR), p21-activated kinase 1 (PAK1), pMAPK, bcl2 and progesterone receptor. RESULTS: Pser118ER staining was higher in Her2- (P = 0.06), IGFR- (P = 0.0002) and pMAPK-expressing tumors (P = 0.001). The level of ER phosphorylation was not different according to the occurrence of clinical tumor response (P = 0.16). Pser118ER expression was significantly reduced by endocrine therapy. The mean Pser118ER score was 163 [standard deviation (SD) 81] before endocrine therapy and 80 (SD 90) after endocrine therapy (P = 0.0001, paired t-test). The magnitude of Pser118ER decrease was higher in tumors that responded to endocrine therapy (mean decrease 128, SD 86) as compared with refractory tumors (mean decrease 38, SD 130) (P = 0.017, t-test). CONCLUSION: These findings suggest that endocrine therapy modulates ER on ser118. Pser118ER immunostaining could be used as surrogate marker to monitor treatment efficacy.

Primary small intestinal lymphoma in adults. A comparative study of IPSID versus non-IPSID in the Middle East.

Seventy-five cases of primary small intestinal lymphoma (PSIL) were diagnosed in adults at the American University of Beirut Medical Center (AUBMC) during the period from 1961 to 1980. Two additional cases of immunoproliferative small intestinal disease (IPSID) in the premalignant phase also were studied. Thirty-two patients had IPSID; 27 non-IPSID; and in 18 patients it was difficult to distinguish IPSID from non-IPSID. While the former was shown to be a distinct disease entity with characteristic clinical, pathologic, and immunologic features, the latter was found to have no particular features in this part of the world. In addition to alpha heavy chain protein (AHCP) which is the biological marker of IPSID, the most important finding that distinguished the two diseases was that IPSID was always associated with a dense, compact mucosal cellular infiltrate (MCI) that was continuous and uninterrupted all along the length of the small intestine. In non-IPSID, MCI was lacking and the pathology was confined to sites of gross abnormalities. Sites distant to the primary lesion were free of disease. It was reported previously that the MCI in IPSID is characteristically diffuse plasmacytic or lymphoplasmacytic (DLP). Our study indicates that in addition to this infiltrate, the disease may be associated with another type of infiltrate which is follicular lymphoid (FL). Sixteen patients had DLP; ten, FL; and three, mixed infiltrate. The relationship of AHC disease and IPSID is discussed. AHCP may be found in intestinal fluid, serum, within the abnormal cell, or at its surface. Immunofluorescence and immunoperoxidase studies must be done on all intestinal and nodal tissue specimens in all patients with PSIL for the detection of AHCP, particularly in those where serum and intestinal fluid are negative for this protein. The hypothesis that the DLP infiltrate represents the secretory form of IPSID, while the FL the nonsecretory form, is introduced. IPSID is an ideal model for the study of the etiology and pathogenesis of lymphoma in man.

Non-Hodgkin's lymphomas in the Middle East. A study of 417 patients with emphasis on special features.

A total of 417 evaluable patients with non-Hodgkin's lymphomas were diagnosed between January 1974 and December 1983 at the American University of Beirut Medical Center in Beirut, Lebanon. Of these, 179 (43%) patients had nodal lymphomas, and 183 (44%) had extranodal lymphomas. The commonest lymphoma was diffuse large cell (27%), followed by large cell immunoblastic (21%). The histopathologic pattern was follicular in 18% of the nodal lymphomas and in 5.3% of the extranodal forms. The most common site of extranodal lymphoma was the gastrointestinal tract (46.5%), followed by Waldeyer's ring (19%). Small intestinal lymphomas were three times more common than gastric lymphomas. Immunoproliferative small intestinal disease (IPSID) was diagnosed in 20 of 59 patients who had primary small intestinal lymphoma. Of the 34 patients who had Waldeyer's ring lymphoma, 7 had gastrointestinal involvement at some time during the course of the disease. Nodal lymphomas were associated with poor prognostic factors: 82% were diffuse; 77% had advanced disease at presentation; 77% had intermediate- or high-grade malignancy lymphoma; 40% had marrow involvement; and 46% had B symptoms. In children, the most common lymphoma was Burkitt's, and 80% of pediatric lymphomas were high-grade malignancy. In conclusion, this study delineates the special features of non-Hodgkin's lymphomas in the Middle East: The presence of IPSID; the high incidence of extranodal forms, in particular the intestinal ones; and the rarity of follicular lymphomas.

Burkitt's lymphoma in the Middle East. A study of 34 cases.

The clinical features of 34 patients with Burkitt's lymphoma diagnosed at the American University Medical Center (AUMC) are described. Ages ranged between 3 and 20 years (median, 7 years). Seventy-three percent of the patients were younger than 8 years. Three cases occurred among siblings. The primary site of disease at presentation was the abdomen, 23 patients; jaw, 6; jaw and abdomen, 2; Waldeyer's ring, 2; and mediastinum, 1. Of those who had abdominal disease, the involvement was diffuse and extensive in abdomen and pelvis in 9, apparently confined to the ileocecal region in 5, mesenteric nodes and small intestine in 5, large intestine in 1, and ovary in 3. One patient presented with paraplegia. The bone marrow was studied in 19 patients; it was positive in 5 and suspicious in 2. None had frank leukemia. CSF was studied in 4 patients at presentation and was negative. Eight patients developed meningeal lymphoma during the course of the disease. Liver involvement was documented in 3 patients. Peripheral lymphadenopathy was observed at presentation in 11 patients (9, neck; 2, inguinal + axillary). In contrast to African Burkitt's, the majority of our patients presented with abdominal disease, and in contrast to the American form, our patients were younger with a median age similar to that of African Burkitt's. Thirty percent of the patients had jaw tumor at presentation--a figure intermediate between the African and the American Burkitt's.

Burkitt's lymphoma in the Middle East.

The clinical features of 30 retrospectively diagnosed cases of Burkitt's lymphoma (BL) at the American University Medical Center (AUMC) in Beirut differed from those of African Burkitt's in that the majority of the AUMC patients presented with abdominal disease, and from the American form, in that the AUMC patients were younger, with a median age similar to that of African BL patients.