Prognostic significance of PU.1 in follicular lymphoma.

Very few prognostic factors are known in follicular lymphoma (FL), a common malignancy of germinal centre (GC) B-cells. The Follicular Lymphoma International Prognostic Index (FLIPI) thus far appears to be the most important predictor of clinical outcome. This study explores the predictive power of the degree of GC differentiation for outcome in FL. Samples from 73 patients with FL were evaluated by immunohistochemistry for expression of GC markers. Strong PU.1, CD20, and CD75 expression were significantly associated with longer progression-free survival (PFS) and overall survival (OS). Results for PFS were independent of the International Prognostic Index or the Italian Lymphoma Intergroup prognostic index for CD75 and PU.1, but only PU.1 expression was independent of FLIPI for PFS and OS. Oct-2 was weakly expressed overall, but more strongly in higher grades of FL; it had a trend for negative linear association with PU.1 and strong positive linear association with CD27, which possibly reflects its role in terminal B-cell differentiation. We show that the level of GC differentiation, as determined by the levels of PU.1, CD75, CD20, Bcl-6, and CD10 expression, has an association with outcome in patients with FL. While this is determined qualitatively in most studies of diffuse large B-cell lymphoma, in FL there is a quantitative positive association between a high level of expression of GC antigens and longer OS and PFS even when data are stratified by the FLIPI score.

Prognostic significance of DNA ploidy determined by high-resolution flow cytometry in breast carcinoma.

OBJECTIVE: To assess the prognostic value of DNA ploidy in breast carcinoma and its relation to other established prognostic factors. STUDY DESIGN: We evaluated DNA ploidy in 303 breast carcinoma patients with a median follow-up of 63 months. Flow cytometry was performed on frozen tumor material, yielding histograms with narrow peaks (median coefficient of variation of 2.08). DNA ploidy pattern was classified as either diploid versus nondiploid, euploid (diploid and tetraploid) versus aneuploid or diploid/near-diploid (DNA index < 1.2) versus other, and correlated with relapse-free (RFS) and cancer-specific survival (CSS) along with tumor size, histologic grade and type, axillary lymph node involvement, menopausal and steroid receptor status, age and type of treatment. RESULTS: Seventy-one percent of tumors were DNA nondiploid (14% tetraploid and 57% aneuploid). There was a strong association between DNA ploidy and histologic grade. Histologic grade, lymph node status, tumor size and DNA ploidy (regardless of the classification used) were all significantly associated with RFS and CSS in multivariate analysis. CONCLUSION: These results suggest that DNA ploidy, at least when determined from frozen tumor tissue, is an independent prognostic factor in breast carcinoma; however, its prognostic power seems to be inferior to that of histologic grade, with which it strongly correlates.

Small cell carcinoma of the liver: a hitherto unreported variant of hepatocellular carcinoma.

We report three cases of an unusual primary carcinoma of the liver composed of small cells. The patients were adult males (56 to 89 years) who presented with jaundice, weight loss and abdominal discomfort. Surgery was attempted in one case. Clinical evolution was rapid, with death ensuing between 1 and 5 months after diagnosis. Surgical (1 case) and autopsy (2) tissues were available for review. All three tumours arose in non-cirrhotic livers. They were composed of broad nests of small epithelial cells with little supporting tissue. They were positive for low-molecular weight keratins and alpha-fetoprotein. One case was immunoreactive for erythropoietin antigen. Expression of neuroendocrine markers was focal and erratic. No immunostaining was observed for carcinoembryonic antigen or S-100 protein. In one case ultrastructural investigation disclosed canaliculi surrounded by microvilli and junctional complexes. In the light of these features, it appears that small cell carcinoma represents a rare, but definite variant of hepatocellular carcinoma. Although it does not segregate in a peculiar clinical setting, it should be distinguished from metastatic pulmonary small cell carcinoma as well as from other malignancies featuring small cells.

Acinic cell-like carcinoma of the breast.

A case of infiltrating carcinoma of the breast with features similar to those seen in acinic cell carcinoma of the parotid gland is described in a 42-year-old woman. The neoplastic cells were immunoreactive with anti-lysozyme- and anti-salivary-type amylase antisera and contained electron-dense cytoplasmic globules similar to those seen in acinic cell carcinoma of salivary glands. One lymph node out of 18 was found to contain a metastatic deposit. The patient is alive and well 1 year after mastectomy. This appears to be the first case of carcinoma with acinic cell-like features reported in the breast.

Epithelioid sarcoma in FNAB smears.

FNAB smears of eleven epithelioid sarcomas were reviewed and analysed. Ten cases had a very similar cytomorphologic picture composed predominantly of dissociated epithelioid-like cells with eccentrically placed nuclei. These tumors were clearly malignant but difficult to differentiate morphologically from melanoma, epithelioid leiomiosarcoma, and Schwannoma or adenocarcinoma. One case was composed of spindle cells and was reminiscent of a fibrohistiocytic tumor. Immunocytochemical reactions to vimentin and cytokeratin were performed in six cases on the Papanicolaou stained smears. The reactions to both antigens were positive in all six cases. Ultrastructural characteristics of eight of the tumors are also described. It seems that epithelioid sarcoma has a rather distinct cytomorphologic picture. Taking into consideration clinical data and using also immunocytochemistry, a definitive diagnosis of epithelioid sarcoma can probably be given from FNAB smears.

Epithelioid angiosarcoma of the thyroid gland. Report of two cases.

We present two cases of epithelioid angiosarcoma of the thyroid gland from two patients in Slovenia. In both cases, the tumor appeared as a dominant nodule in a multinodular goiter. Histological appearance of the tumor was similar in both cases and characterized by large epithelioid tumor cells with numerous intracytoplasmic lumina, large nuclei, and very prominent nucleoli. Such cells formed vascular structures as well. Neoplastic cells were positive for factor VIII-associated antigen in both cases. Reaction to Ulex europaeus lectin was positive in one case, and characteristic ultrastructural features were seen in another case. In both cases, some neoplastic cells also showed keratin positivity. Angiosarcoma is a rare but definite possibility in a differential diagnosis of anaplastic thyroid tumors in Slovenia.

Primary bone sarcoma with rhabdomyosarcomatous component.

We present three cases of primary bone sarcoma with rhabdomyosarcomatous component which in one case appeared in a pure form, i.e., as rhabdomyosarcoma; in the other two cases it presented as one of multiple components of the tumor. The first patient was a 70-year-old man with a tumor of the left femur involving surrounding soft tissue of the thigh. Histologically, this was a case of so-called dedifferentiated chondrosarcoma with pleomorphic rhabdomyosarcoma representing high grade malignant component. The second patient, a 31-year-old man, developed a tumor in the left tibia which was a rare, fibrosarcoma-like type of rhabdomyosarcoma. The third patient was a 43-year-old woman with a tumor in the left tenth rib which was shown to be osteo- and chondrosarcoma with a minor rhabdomyosarcomatous component and was classified as malignant mesenchymoma. All patients were treated by surgery and chemotherapy. The first two of them died of metastatic disease 3 months, and 3 years and 4 months following surgery, respectively. Light microscopical diagnosis of rhabdomyosarcoma of hematoxylin-eosin sections was confirmed immunohistochemically in each case using reactions to desmin, muscle specific actin and myoglobin, and ultrastructurally in two cases. Rhabdomyosarcomatous component in primary bone tumors appears to be rarely present but more cases may be diagnosed in the future, if immunohistochemical and ultrastructural examinations are to be employed.

Sclerosing inflammatory pseudotumor of the urinary bladder in a child.

A case of inflammatory pseudotumor of the urinary bladder in a 2-year-old child is presented. It was characterized by nodular intravesical growth and massive infiltration of the bladder wall. Microscopically, the lesion showed in its largest part a relatively paucicellular spindle cell growth and a sclerotic appearance with a thin superficial cellular zone resembling granulation tissue. Another morphological characteristic was a marked capillary proliferation revealed by immunohistochemical reactions to factor VIII-associated protein, laminin, and collagen IV. The last feature appears to be an integral part of the process, which most closely resembled fibromatosis of the adult type, a rare pattern of growth in inflammatory pseudotumor.

Association of leptomeningeal carcinomatosis in carcinoma of the breast with infiltrating lobular carcinoma. An autopsy study.

We analyzed the autopsy records of 261 patients with breast carcinoma, who died at The Institute of Oncology, Ljubljana, Yugoslavia, for the presence of metastases to the central nervous system, particularly for the presence of leptomeningeal carcinomatosis. Metastases to the central nervous system were found in 41 (18.1%) of 226 patients who had metastatic cancer. In 24 cases (10.6%), metastases were seen in brain parenchyma; in 11 cases (4.9%), only dura mater was involved, and in six cases (2.6%), leptomeningeal carcinomatosis was found. All patients with leptomeningeal carcinomatosis showed some symptoms of central nervous system involvement while alive. The patients died between 2 weeks and 2 months after the onset of central nervous system symptoms. Four of six patients with such a complication presented with locally advanced or disseminated carcinoma on the first admission. With regard to histologic findings, three patients had infiltrating lobular carcinoma, two had infiltrating ductal carcinoma, and one had mixed infiltrating lobular and ductal carcinoma, with a metastasizing lobular component. Metastases to the brain parenchyma were found exclusively in infiltrating ductal carcinoma. We stress that infiltrating lobular carcinoma represents a distinctive type of breast cancer with an unusual propensity to disseminate into leptomeninges, as this occurred in almost 14% of all cases of infiltrating lobular carcinoma in our series in contrast to a 1% incidence in cases of infiltrating ductal carcinoma.

Epithelioid hemangioendothelioma of the anterior mediastinum with osteoclast-like giant cells. Light microscopic, immunohistochemical, and electron microscopic study.

A case of epithelioid hemangioendothelioma of the anterior mediastinum in a 40-year-old woman is presented. It showed typical features described in such tumors, but in addition there were foci of osteoclast-like giant cells that were not previously reported in this lesion.

Adenoid cystic carcinoma of the breast: a histologic, cytologic, and immunohistochemical study.

Six cases of adenoid cystic carcinoma (ACC) of the breast were reviewed. Immunohistochemical studies were carried out for actin, S-100 protein, EMA, keratin, CEA, vimentin, NSE, alpha-lactalbumin, and lysozyme. Fine needle aspiration biopsy smears of five patients were also reexamined. Patients were treated by tumorectomy, quadrantectomy, or modified radical mastectomy. Axillary dissection was carried out in five cases, with negative lymph nodes in all. Five patients are alive without evidence of disease from 1 year 10 months to 13 years 4 months following surgery. One patient died 7 1/4 years after mastectomy, without evidence of disease. Histologically, a diagnostic biphasic cellular pattern was seen in all cases. In addition, several unusual features were encountered in some cases: squamous metaplasia, stromal myxoid pseudocartilaginous foci, and well-formed neoplastic ducts. Actin and/or S-100 protein were variably positive in all cases. The reaction was usually present in occasional basaloid cells predominantly at the periphery of neoplastic structures. Keratin, EMA, and CEA immunostaining disclosed ductal type cells in all cases. Vimentin was positive in four cases, usually in many basaloid cells. Aspiration cytology was suspicious in two cases and yielded a definitive diagnosis of ACC in three cases. Cytologic diagnosis was based on cellular morphology and on the presence of characteristic globoid structures. Immunohistochemical results show that in ACC dual myoepithelial-ductal differentiation occurs but is relatively limited. Most of the tumor cells are not differentiated ("indifferent" cells) and often express strong vimentin positivity. Such cells are regarded as precursor cells for either differentiated element. Unusual metaplastic changes in breast ACC suggest a possible relation with pleomorphic adenoma-type tumors, and this might be of prognostic significance.