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Background. Cathepsin D is an estrogen-regulated lysosomal protease that may be overexpressed in breast cancer. Several studies based on biochemical analysis of tumor cytosol have shown that high levels of cathepsin D are associated with poor outcome in patients with breast cancer. In contrast, a few immunohistochemical studies have shown that cathepsin D positivity in breast cancer cells indicates a favorable prognostic outcome or is of no prognostic significance. Methods. Because of the current controversy, the authors studied, using immunohistochemistry, the distribution (0 to 3) and intensity (0 to 3) of cathepsin D in Stage I and II infiltrating ductal carcinoma of the breast from 245 patients treated at the City of Hope National Medical Center, Duarte, California, from 1970 to 1986. A commercially available rabbit antiserum to purified human cathepsin D and the standard avidin-biotin complex method were used. Statistical analysis was based on a combined low (0 or 2) or high (3 to 6) score. Results. A high cathepsin D score was associated with Stage II disease (P = 0.007), positive lymph nodes (P = 0.019), high nuclear grade (P = 0.005), and c-erbB-2 oncogene amplification (P = 0.013). Cathepsin D positivity was not an independent prognostic indicator of disease-free survival (DFS) or overall survival (OS). In a subgroup analysis, the presence of cathepsin D had only a modest association with predicting a shorter DFS in patients with negative lymph nodes (P = 0.072) or positive progesterone receptors (PR) (P = 0.086). Conclusions. Immunohistochemical analysis of cathepsin D, with the antiserum used in this study, is not an independent predictor of outcome in patients with breast cancer because of its strong associations with several well-established prognostic indicators. Cancer 1993; 71:2756-63.

It is very unusual for tumors growing in the lungs to form cavities. Consequently, there is a risk of failing to properly identify cystic tumors in the chest. This problem is illustrated by two case histories of patients with cystic metastatic sarcoma in the lungs. The cancers could not be identified by chest X-ray. The lesions could be seen on computed tomography (CT) of the chest, but they had the appearance of benign bullous disease, which involves the formation of large vesicles or bullae. Upon removal of the cysts, the lack of any solid cancerous tissue for examination, and the variability of the tissue comprising the cyst wall, made histopathological analysis difficult. The definitive diagnosis was made on the basis of specific immunochemical staining of the tumors, which were identified as a smooth muscle tumor, or leiomyosarcoma, in one patient and a sarcoma of the synovium in the other. It is clear that thin-walled bullae, which appear benign on CT scan, must be considered potentially malignant and removed surgically when appropriate. (Consumer Summary produced by Reliance Medical Information, Inc.)

Symptomatic involvement of the small bowel by isolated metastasis from an extra-abdominal primary malignancy is rare, most commonly resulting from malignant melanoma and lung cancer. A few other extra-abdominal tumors, not including thyroid cancer, have been documented on rare occasions to present with small-bowel involvement as the first evidence of metastasis. We report a case of anaplastic thyroid carcinoma with isolated symptomatic metastasis to the small intestine. We review the literature regarding the frequency and origin of extra-abdominal malignancies developing small-bowel metastases and the spectrum of clinical manifestations resulting from this syndrome.

Rearrangement of the BCL-2gene is the molecular consequence of the t(14;18) chromosomal translocation, which is found in ∼60–90 of follicular lymphomas. To investigate the ability of the polymerase chain reaction (PCR) to detect this rearrangement in fixed-tissue samples. we studied 48 cases of follicular lymphoma using DNA extracted from paired samples of fresh-frozen tissue and formalin-fixed, paraffin-embedded tissue. A standard phenol-chloroform DNA extraction method was used for both types of tissue. Rearrangements of the major breakpoint region (MBR) and minor cluster sequence (MCS) were examined. Three segments of the human β-globin gene were also amplified to estimate the degree of DNA degradation in the fixed-tissue samples. PCR of fresh-tissue (intact) DNA revealed amplifiable products in 29 of the 48 follicular lymphomas (60), whereas the fixed-tissue (degraded) DNA studies were positive in 24 (50). MBR products were detected in 24 fresh-tissue samples, and varied from 80 bp to >1.5 kb. Twenty of these cases yielded MBR products in the corresponding fixed-tissue DNA. ranging from 80 to 276 bp. Five fresh-tissue and four fixed-tissue samples produced MCS segments that ranged from 340 bp to 1.2 kb. Four of the five samples with no detectable MBR or MCS translocations using degraded DNA had products greater than 1.0 kb in the fresh-tissue studies. A 175-bp segment of the (3-globin gene was amplified in all 29 fixed-tissue samples; a 324 bp fragment was produced in 20 samples (69), and a 676 bp segment was detected in 13 (45). These studies show that PCR performed with DNA extracted from formalin-fixed tissue can detect and accurately size approximately 80 of the BCL-2gene rearrangements evident with intact high-molecular-weight DNA, and that the majority of falsely negative fixed-tissue samples have translocation products above 1.0 kb. Furthermore, by amplifying three successively larger segments of the human β-globin gene, we have shown that the degradative effect of formalin fixation on DNA extracted from clinical samples is gradual and progressive, at least up to a size of 676 nucleotides.

Acute leukemias containing >3 myeloperoxidase (MPO)-positive blast cells, as detected cytochemically, are considered to be myelogenous in origin, regardless of the immunophenotypic markers expressed. Conversely, acute leukemias that express only myeloid antigens are also considered to be acute myelogenous leukemia (AMD, even in the absence of MPO. These MPO-negative AMLs, designated AML-M0 in the FAB classification, currently require either immunophenotypic or electron microscopic studies for identification. To examine the association of MPO and myeloid antigen expression in AML, particularly at the early stages of myeloid cell differentiation, we have used in situ hybridization (ISH) to evaluate MPO gene expression in myeloid leukemia cell lines and a variety of well-characterized acute leukemias, including six cases of AML-MO. Strong positivity for MPO mRNA was detected in the myeloid leukemia cell line HL-60 and in 22 of 27 AMLs (three AML-MO, four AML-M1, eight AML-M2, five AML-M4, two AML-M5a). No MPO gene expression was detected in three AML-MO, one AML-M5a, one AML-M7, 5 acute lymphoblastic leukemia, the lymphoid cell lines Molt-4 and Namalwa, or in the early myeloid cell lines KG-1 and KG-la. Ultrastructural studies for MPO activity were performed on four AML-M0; one leukemia showed both gene expression and cytochemical activity, whereas two others contained neither MPO transcripts nor enzyme. Weak MPO gene expression was evident in one AML-M0 that was negative for enzymatic activity by electron microscopy. These studies show that MPO gene expression can be detected by ISH in about half of AML-M0, supporting their presumed myelocytic derivation. However, the blasts in some AML-M0 fail to express MPO, even at the molecular level, suggesting that these cells are at a very early stage of myeloid commitment or that differentiation along some other nonlymphoid cell line may be present.

Blast cells from 100 cases of acute leukemia were evaluated for the presence of methylthioadenosine phosphorylase (MTAase), an enzyme important in polyamine metabolism. Ten cases (10%) had undetectable levels of MTAase activity. Of the 10, 5 had acute lymphoblastic leukemia (ALL), 3 had acute myeloblastic leukemia (AML) and 2 expressed mixed lineage markers as determined by immu-nophenotyping. A relatively high frequency (38%) of MTAase deficiency was seen in ALL of T-cell origin. Nonmalignant hematopoietic cells from three patients with MTAase-deficient leukemias had readily detectable enzyme activity. Chromosomal abnormalities were detected in four of the seven MTAase-deficient cases in which karyotypic analysis was performed. No consistent karyotypic defect was apparent, and only one case displayed changes in chromosome 9, the putative location of the MTAase structural gene. The clinical findings among the enzyme-deficient cases were unremarkable except that all patients were male (P < .01). Only one patient had “lymphomatous” features. We conclude that MTAase deficiency occurs in a wide variety of acute leukemias, that the lack of enzyme activity is specific to the malignant cells, and that an increased incidence occurs in ALL of T-cell origin. Furthermore, no specific gross chromosomal abnormality is associated with the enzyme deficiency. The marked male predominance in patients with MTAase-deficient acute leukemias suggests involvement of the X chromosome in the loss of enzyme activity. The absence of MTAase in some leukemias may be therapeutically exploitable. © 1988 by Grune & Stratton, Inc. 0006-4971/88/7106-0004$ 3.00/0

Monocytoid B-cell lymphoma (MBCL) is a newly recognized B-cell neoplasm of uncertain histogenesis. The cytologic features of the neoplastic monocytoid B lymphocytes are virtually identical to those of hairy cell leukemia (HCL). As with HCL, progression of MBCL to a higher histologic grade is very unusual. However, whereas circulating leukemic cells are a characteristic feature of HCL, peripheral blood involvement has not been reported in MBCL. We recently studied a patient with MBCL of the spleen and axillary lymph nodes who developed peripheral blood involvement by MBCL cells. Unlike the cells of HCL, the circulating MBCL cells exhibited strong acid phosphatase activity that was tartrate sensitive. The leukemic cells had the antigenic phenotype IgMλ, CD20+, CD11c+, CD5-, CD25(TAC)-, and PCA-1-. Immunogenetic studies of both lymph node and peripheral blood cells revealed identical immunoglobulin heavy-chain gene rearrangements. When compared with a series of HCL, the immunophenotype was similar except for the absence of PCA-1 and TAC. Progression of the MBCL to a large cell lymphoma, also expressing IgMλ, was documented in an abdominal lymph node of this patient. Therefore, although rare, peripheral blood involvement by lymphoma cells may occur during the course of MBCL and should be distinguished from HCL with cytochemical and immunophenotypic studies. In addition, comparison of the clinical, pathologic, and immunologic features of MBCL with those of other low-grade B-cell neoplasms suggests that a close lineage relationship exists between MBCL and HCL.