Assessment of gonadal function in boys and adolescents at the diagnosis of neoplastic disease.

OBJECTIVE: We assessed the gonadal function in boys with a newly diagnosed neoplastic disease prior to chemotherapy. Eighty-four boys (48 prepubertal and 36 pubertal) were evaluated, including 50 with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL), 10 with Hodgkin lymphoma (HL), and 24 with solid tumors. The control group consisted of 24 healthy prepubertal and 24 pubertal boys. The levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, and testosterone were determined, and testicular volumes were measured. RESULTS: Patients in prepuberty and early puberty (Tanner stages 1-3) diagnosed with ALL/NHL or solid tumor presented normal serum reproductive hormone levels, whereas in ALL/NHL patients in Tanner stages 4-5, the mean values of inhibin B were significantly lower (45.18 +/- 33.85 vs. 153.57 +/- 71.44 ng/L, p = 0.0027). In patients with HL in Tanner stages 4-5, a statistically significant lower mean inhibin B level (100.44 +/- 67.45 versus 153.57 +/-71.44 ng/L, p = 0.0027), higher mean FSH level (6.3 +/- 3.6 versus 4.6 +/- 2.2 mIU/mL, p = 0.05), and higher mean LH level (5.9 +/- 4.0 versus 3.6 +/- 1.8 mIU/mL, p = 0.05) were observed. No statistically significant differences were noted in assessed hormones in patients with solid tumors, independently of Tanner stage. CONCLUSION: Our analysis indicates that adolescents with ALL/NHL and HL prior to treatment, exhibit reduced levels of inhibin B, which indirectly suggests the possibility of spermatogenesis dysfunction.

[The morphological assessment of bone marrow infiltration in neuroblastoma]. / Valutazione morfologica dell'infiltrazione midollare nel neuroblastoma.

Bone marrow biopsy is very important in diagnosis and follow-up of children affected by neuroblastoma (NB). Between June 1995 and May 1997 we studied 55 patients with NB stage 4. Specimens were obtained at the diagnosis (in 8 patients) and after chemotherapy (in 55 patients) in order to evaluate the effects of treatment on bone marrow disease. 88% of 343 biopsies were representative versus 99% of 639 aspirates. Of 8 stage 4 patients evaluated at diagnosis, 15/16 biopsies versus 9/15 aspirates were positive. Following chemotherapy, out of 298 evaluable sites examined, 111 biopsies versus 30 aspirates (37 versus 10%) were positive. Of 111 positive biopsies 53 showed a focal pattern (35 differentiated, 18 undifferentiated), while 51 showed a diffuse pattern (18 differentiated, 40 undifferentiated). Our results confirm previous literature data indicating a better efficacy of histology versus morphology in detecting residual bone marrow disease (especially in case of focal differentiated pattern). The recent introduction of a specific monoclonal antibody, called anti-GD2, has improved our capacity to detect minimal residual disease in patients' bone marrow. The inclusion of anti-GD2 immunohistochemistry in our evaluation will possibly increase our overall sensitivity to detect minimal residual disease and may provide information capable to direct the physician's decision into a more rational patient's treatment.

Paragangliomas: assessment of prognosis by histologic, immunohistochemical, and ultrastructural techniques.

To predict clinical outcome, we studied 42 paragangliomas from 37 patients by routine histology, immunohistochemistry, and electron microscopy. A panel of antisera to neuron-specific enolase (NSE), chromogranin, and met-enkephalin was used to identify chief (type I) cells, and S-100 protein and glial fibrillary acid protein (GFAP) sustentacular (type II) cells. The intensity of staining of type I cells and the density of type II cells were assessed semiquantitatively (0 to 4+) in a total of 38 tumors. A total of 23 of 24 low-grade tumors (solitary, multiple, or associated with other neoplasms; 95.8%) contained type II cells immunoreactive with either S-100 protein or GFAP, and all were positive when S-100 protein and GFAP were used in combination. Five of the nine intermediate-grade (recurrent and/or locally aggressive) tumors were identified as glomus jugulare tumors (GJT). Three intermediate-grade GJTs were devoid of GFAP-reactive type II cells and four GJTs were negative for S-100 protein. Type II cells were identified in only one of five high-grade (malignant) paragangliomas and that tumor contained vanishingly rare cells that were weakly S-100 protein positive but GFAP negative. Sustentacular cell density and chief cell staining intensity were both inversely related to tumor grade. The most sensitive chief cell marker was NSE (92.1%), followed by chromogranin (84.2%). The least sensitive (73.0%) and specific marker was met-enkephalin. Combinations of NSE or chromogranin with met-enkephalin identified chief cells in all cases. Electron microscopy identified neurosecretory granule-containing chief cells, but was of less value in delineating sustentacular cells because of their scarcity and the absence of specific features. By comparison, immunohistochemistry was superior in identifying sustentacular cells. The use of an immunohistochemical panel, in addition to routine histology, can confirm the diagnosis of a paraganglioma and can give an indication of the likely prognosis for a patient.