Analysis of genomic breakpoints in p190 and p210 BCR-ABL indicate distinct mechanisms of formation.

We sought to understand the genesis of the t(9;22) by characterizing genomic breakpoints in chronic myeloid leukemia (CML) and BCR-ABL-positive acute lymphoblastic leukemia (ALL). BCR-ABL breakpoints were identified in p190 ALL (n=25), p210 ALL (n=25) and p210 CML (n=32); reciprocal breakpoints were identified in 54 cases. No evidence for significant clustering and no association with sequence motifs was found except for a breakpoint deficit in repeat regions within BCR for p210 cases. Comparison of reciprocal breakpoints, however, showed differences in the patterns of deletion/insertions between p190 and p210. To explore the possibility that recombinase-activating gene (RAG) activity might be involved in ALL, we performed extra-chromosomal recombination assays for cases with breakpoints close to potential cryptic recombination signal sequence (cRSS) sites. Of 13 ALL cases tested, 1/10 with p190 and 1/3 with p210 precisely recapitulated the forward BCR-ABL breakpoint and 1/10 with p190 precisely recapitulated the reciprocal breakpoint. In contrast, neither of the p210 CMLs tested showed functional cRSSs. Thus, although the t(9;22) does not arise from aberrant variable (V), joining (J) and diversity (D) (V(D)J) recombination, our data suggest that in a subset of ALL cases RAG might create one of the initiating double-strand breaks.

Prognosis in colorectal carcinoma. A reassessment of the pathologist's role.

The prognostic significance of some pathologic features was evaluated in a series of 177 patients with colorectal carcinoma consecutively treated by curative resection in a department of Surgery from 1960 to 1981. There were 90 men and 87 women with a mean age of 59.2 +/- 12.8 and a range from 23 to 88 years. Current follow-up information was obtained in 92.7% of the patients. Pathologic staging as classified according to a modification of Dukes' original scheme was found to be the most important prognostic factor. Evaluation of lymphatic and venous invasion, histologic differentiation, and site of tumors also provided valuable prognostic information. Size, configuration, mucin-producing ability and the morphologic evaluation of the so-called "host immunologic response" were found to be irrelevant for the prognosis when the influence of the other indices was controlled.

Prognostic significance of some pathologic factors in breast carcinoma.

The prognostic significance of several pathologic factors was analysed in a series of 221 cases of breast carcinoma consecutively and primarily treated in a department of surgery. It was found that the outcome of patients could be fairly well outlined in routine practice using the axillary nodal involvement (absence or presence of metastases and number of "positive" nodes), tumor size as measured in surgical specimens and histopathologic evaluation. It was also found that the predictive value of tumor grading is clearly enhanced when it is used in combination with the histological classification. The histological pattern and sinus histiocytosis of regional lymph nodes, as well as the lymphoid infiltration of the tumors, were also found to have some prognostic importance. The presence of vascular invasion in primary tumors of patients with nodal metastases as well as the finding of extranodal extension did not provides additional prognostic information.

Hürthle-cell lesions of the thyroid: a combined study using transmission electron microscopy, scanning electron microscopy, and immunocytochemistry.

Hürthle cell transformation found in 2 nodular goiters, 2 cases of Hashimoto's thyroiditis, 4 follicular adenomas, 3 follicular carcinomas, 2 papillary carcinomas and 1 anaplastic carcinoma were studied by transmission electron microscopy, scanning electron microscopy and immunocytochemistry. Ultrastructural features of Hürthle cells were identical in non-neoplastic and neoplastic lesions. Cells crammed with mitochondria, showing abnormalities in size, shape and content were prominent in most cases. The presence of distinct smooth-surfaced cells interspersed with cells with many microvilli is almost a pathognomonic scanning electron microscopic feature of benign and malignant Hürthle cell lesions. Most Hürthle cells stained positively for thyroglobulin in all cases, but no immunoreactivity for CEA and calcitonin was found.

Hürthle cell and mitochondrion-rich papillary carcinomas of the thyroid gland: an ultrastructural and immunocytochemical study.

Of 52 consecutive papillary carcinomas of the thyroid, the following cases were included in this study: one Hürthle cell papillary carcinoma, one papillary carcinoma with foci of Hürthle cells, and 10 cases of papillary carcinoma with abundant mitochondria (volumetric density of mitochondria greater than or equal to 20%). All cases were studied by light microscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and immunocytochemistry. Our results showed that papillary carcinomas mainly or exclusively composed of Hürthle cells are very rare; that Hürthle cell papillary carcinomas of the thyroid share the biologic characteristics and blend insidiously with the so-called mitochondrion-rich papillary carcinomas; that TEM and SEM can provide useful evidence for achieving the differential diagnosis between Hürthle cell and so-called mitochondrion-rich papillary carcinomas; and that immunocytochemical studies are useless in the aforementioned differential diagnosis.

High relative frequency of thyroid papillary carcinoma in northern Portugal.

Two hundred and twelve papillary and 40 follicular carcinomas were found in 3002 thyroid glands examined from 1931 to 1975 in four Laboratories of Pathology that fairly cover northern Portugal. There was a striking preponderance of women both in papillary (female:male = 6.9:1) and follicular carcinoma (5.7:1). Sex-specific frequency of malignancy was significantly greater in men (13.3%) than in women (8.8%). The overall papillary/follicular ratio was 5.3:1 and did not significantly change throughout the study period. Papillary/follicular ratio was not significantly greater in litoral (5.5:1) than in regions with a low iodine intake and a relatively high prevalence of goiter (3.5:1). It is advanced that this high relative frequency of papillary carcinoma in northern Portugal, even in goiter areas, may reflect the existence of a racial factor since there is not enough evidence to support the influence of dietary iodine, previous irradiation and concurrent thyroiditis.

Hughes-Stovin syndrome with pulmonary angiitis and focal glomerulonephritis: a case report with necropsy study.

A clinicopathologic case of Hughes-Stovin syndrome with pulmonary eosinophilic angiitis and focal proliferative extracapillary glomerulonephritis is reported.

Prognostic significance of Lauren and Ming classifications and other pathologic parameters in gastric carcinoma.

One hundred seventy-two patients with gastric carcinoma were studied (111 men and 61 women). Mean age was 54.0 +/- 11.2 years, and the overall five-year survival rate was 37.5%. There were four carcinomas in situ and one double carcinoma; the remaining 167 were classified as intestinal (112), diffuse (48), and atypical (7), according to Lauren; and as expanding (96) and infiltrative (71), according to Ming. Both classifications had prognostic significance; that of Lauren's could not be ascribed to sex and age of patients, to location of tumors, or to extent of disease, but appeared to be associated with the histologic pattern of regional lymph nodes. The prognostic significance of Ming's classification did not seem to depend upon sex and age of patients, location of tumors, or lymphoid response, but appeared to be partially related with extent of disease. The concurrent use of both classification did not provide further prognostic information.

Mediastinal and hilar fibrosis.

A case is described of mediastinal and hilar fibrosis in a woman aged 22 years. The fibrotic mass compressed the lobar arteries as well as the veins of various lobes of both lungs. These large vessels as well as numerous smaller arteries and veins were to a large extent obstructed by organized thrombi. It seems likely that 3 years after the beginning of symptoms the fibrosing process was still active. The case provides some support for an immunopathological aetiology of this condition.

Comparative morphometric study of cerebellar neurons. I. Granule cells.

Several differences concerning granule cell characteristics have been reported in phylogenetic studies. In this work, the granule cell features of 4 frogs, 4 pigeons, 4 rats, 4 cats and 6 human subjects were determined using morphometric methods. Frog granule cells showed a significantly greater volume and a significantly lower numerical density in comparison with the other species; nevertheless no significant differences were found concerning their organelles. The volume of granule cells was significantly smaller in man than in the other two mammal species but no significant differences were observed in their numerical densities. A significant negative correlation was found between the mean cellular volume and the numerical density of granule cells in every species. These results support the assumption that the biological development of the human cerebellar granular layer is accompanied by a miniaturization of the granule cells, in a way similar to that previously suggested for cerebral neurons.

Comparative morphometric study of cerebellar neurons. II. Purkinje cells.

The morphometric characteristics of Purkinje cell perikarya and dendritic trees were evaluated in 4 men, 4 cats and 4 rats. Purkinje cell perikaryon size, as well as the number of synapses and the synaptic surface per Purkinje cell, are significantly greater in man than in the cat and the rat. No significant differences were found as concerns the volumetric densities of nuclei and nucleoli. It is advanced that the higher number of synaptic afferences per Purkinje cell in man may represent the morphological counterpart for the increased resolution of the human mossy fiber-granule cell afferent system.