Six cases of malignant fibrous histiocytoma of the canine spleen.
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Actins↗
Biomedical subjects
J J Brooks
Publications and source records attributed to J J Brooks.
Platelet-derived growth factor receptor (beta-subunit) immunoreactivity in soft tissue tumors.
Using a well characterized monoclonal antibody (PR7212) to the beta-subunit of the platelet-derived growth factor receptor (PDGF-R(beta) and the avidin-biotin peroxidase method on frozen sections, we analyzed PDGF-R(beta) expression in 71 nonepithelial lesions as well as normal mesenchymal tissues. PDGF-R(beta) reactivity was observed in normal salivary gland, normal cutaneous and visceral fibroblasts, muscularis mucosa of bowel, and endothelial cells; squamous carcinoma was negative. Interestingly, hepatocytes and lymph node histiocytes were also positive. Positive tumors included malignant fibrous histiocytoma (6/6), benign and malignant smooth muscle tumors (5/6 leiomyoma, 8/9 leiomyosarcoma), liposarcoma (4/4), synovial sarcoma (6/7), angiosarcoma (2/2), and sarcoma NOS (2/2). Fibromatosis cases were also positive (2/2). In many tumors, the reactive fibroblasts and vascular components were also reactive. The characteristic pattern of reactivity in fibroblastic lesions highlighted thin cytoplasmic extensions or strands not visible in normal hematoxylin and eosin-stained sections. Expression of PDGF-R(beta) was not necessarily correlated with the presence of PDGF. We conclude that PDGF-R(beta) expression can be identified in a wide variety of mesenchymal lesions and postulate that its presence may be important in the mechanism of growth of these tumors.
Adenocarcinoma↗
Signet cell melanocytic lesions.
Malignant melanoma can produce diagnostic problems for the histopathologist because of its protean histologic patterns. The recently recognized signet cell pattern can be particularly confusing and must be distinguished from adenocarcinoma, tumors of vascular endothelium or adipose tissue, lymphoma, and epithelioid smooth muscle lesions. We report four new cases of signet cell melanoma and illustrate this pattern in primary as well as metastatic sites. In addition, we document the signet cell pattern in benign nevi for the first time, expanding the concept of this pattern to melanocytic cells in general. The differential diagnosis of signet cell melanoma and its mimics is discussed and the utility of immunohistochemical stains in this diagnosis is stressed.
Adult↗
Cytokeratin immunoreactivity in malignant fibrous histiocytoma and spindle cell tumors: comparison between frozen and paraffin-embedded tissues.
Cytokeratin (CK) immunoreactivity in malignant fibrous histiocytoma (MFH) and other selected cases of spindle cell tumors were assessed using two cytokeratin monoclonal antibodies, AE1/AE3 and CAM 5.2. Frozen tissue was used to minimize the effects of fixation on keratin antigenicity; in addition, one block of fixed, paraffin-embedded tissue was tested for comparison. CK immunoreactivity was noted in nine frozen tissue samples (7/20 [35%] MFH, 1/3 schwannomas, 1/3 leiomyosarcomas). In the majority of cases, only rare individual positive cells were seen. Of 19 MFH cases in paraffin-embedded tissue, CK immunoreactivity was noted in three (16%). All 32 cases examined showed vimentin immunoreactivity. MFH must be added to the growing list of mesenchymal tumors exhibiting sporadic CK immunoreactivity. Such reactivity is less frequent in paraffin-embedded tissues. This finding has important implications for tumor diagnosis, particularly in the differential diagnosis of pseudosarcomatous carcinoma. Caution is recommended in the interpretation of CK immunoreactivity, particularly as it relates to speculations regarding histogenesis.
Adult↗
Primary intestinal lymphoma in Crohn's disease: minute tumor with a fatal outcome.
A 54-yr-old man with a 22-yr history of Crohn's disease was found to have a microscopic focus of immunoblastic lymphoma within a segment of small bowel resected to relieve intestinal obstruction. There was no other clinically evident disease. Thirty months later, he developed axillary adenopathy with recurrent lymphoma of the same immunophenotype (IgA lambda) and was given combination chemotherapy, with complete clinical response. Lymphoma recurred 6 months later in the axilla and progressed rapidly over the next 3 months, despite chemotherapy. He developed extensive mediastinal, mesenteric, and retroperitoneal disease with malignant ascites and died 39 months after diagnosis of the incidentally discovered bowel mucosal primary tumor.
Axilla↗
Benign glandular schwannoma.
The vast majority of reported glandular schwannomas, the rarest type of divergent differentiation in nerve sheath neoplasms, have been malignant tumors. We describe a benign glandular schwannoma, less than 1 cm in diameter, that developed in the deep subcutaneous region of the left flank of a 36-year-old woman. The glandular component occurred as a single large cyst with an undulating lining occupying the central one third of the lesion and was lined in large part by a well-oriented, flattened, single cell layer of cuboidal to low columnar cells with a basement membrane. This extremely unusual lesion, apparently the fourth benign instance reported, is important for several reasons: (1) it does not appear to be a result of inclusion of previously postulated dermal adnexal glands; (2) it further establishes the existence of a true benign counterpart of the glandular schwannoma, of which pathologists should be aware; (3) it can be distinguished from the recently reported pseudoglandular schwannoma; and (4) it lends additional support to the concept of a direct metaplastic origin of the epithelial element from the schwannian component because of the focal presence of a maloriented pseudoglandular element.
Adult↗
Lymphomas of the breast. A clinicopathologic and immunohistochemical study of primary and secondary cases.
Primary mammary lymphoma is rare, and little is known about the immunophenotype of such cases. The authors studied both primary and secondary breast lymphomas with a broad panel of T- and B-cell markers using paraffin-embedded tissue and the avidin-biotin immunoperoxidase method. Cases of primary B-cell lymphoma were further tested to determine light and heavy chain type. Thirty-five cases were analyzed, including 16 primary lymphomas. Diffuse large cell lymphoma was present in ten of 16 primary and 14 of 18 secondary cases. Lymphoepithelial lesions in ducts and lobules and frequent vascular involvement were found in both primary and secondary cases. Immunohistochemistry studies on 13 tumors revealed all of the primary tumors to be B-cell in origin, except for one case of primary T-cell lymphoma; to the authors' knowledge, this represents the first description of this entity. Fifteen of 17 secondary tumors exhibited B-cell markers and one of 17 exhibited T-cell markers; in only one case could lineage not be determined. Among primary B-cell cases, IgM was found to be the most frequent heavy chain type; IgA reactivity was found in only one case. Survival was related to stage and histologic characteristics; patients with Stage II disease and higher grade histologic lesions had a worse prognosis. Half of the patients with primary lymphoma have had recurrent disease. Although local recurrences were observed, the authors also saw a tendency for recurrence in other extranodal sites. The authors conclude that, although primary lymphoma of the breast is compatible with long-term survival, a significant number of patients eventually die of their disease. As with other extranodal lymphomas, survival rate appears most related to stage of disease. Also, the vast majority of primary tumors are B-cell in origin, express IgM heavy chain, and can be considered tumors of mucosa-associated lymphoid tissue.
Adult↗
Esophageal sarcomas.
The clinical and pathologic characteristics of five patients with esophageal sarcomas are presented, including the only recorded esophageal Triton tumor (malignant schwannoma), the third recorded synovial sarcoma, two patients with carcinosarcoma, and one with leiomyosarcoma. All five patients were males who presented with dysphagia. Three tumors were in the cervical esophagus, and the remaining two were in the distal esophagus. On endoscopic examination, three of the tumors were noted to be polypoid, while the other two were sessile. Two patients presented with disseminated disease, and a third was locally unresectable. These three patients were treated with palliative intent. The remaining two patients underwent surgical excision and postoperative radiation therapy, and are alive and well 6 and 7 years following treatment. This experience suggests that combined modality therapy employing postoperative radiation may be effective in managing these rare lesions.
Adolescent↗
Pathological and radiographical features of multicentric malignant fibrous histiocytoma in two dogs.
Widespread organ distribution of malignant fibrous histiocytoma, including osseous involvement, was demonstrated in two dogs. Both cases had a storiform-pleomorphic pattern histologically and immunohistochemical stains were used to differentiate this from other types of neoplasms with the same histological pattern. Radiographically the lesions were predominantly lytic in the metaphysis of long bones, although periosteal proliferation and axial skeletal involvement were seen in one dog.
Animals↗
Absence of t(14;18) major and minor breakpoints and of Bcl-2 protein overproduction in Reed-Sternberg cells of Hodgkin's disease.
The t(14;18) translocation, found in most human follicular non-Hodgkin's lymphomas (NHLs), juxtaposes the Bcl-2 oncogene at 18q21 with the immunoglobulin heavy chain locus at 14q32. As a result, the Bcl-2 protein is markedly overproduced. Most of the breakpoints on chromosome 18 cluster at one of two sites, the major breakpoint region (mbr) and the minor cluster region (mcr). Recently, others used the polymerase chain reaction (PCR) to detect the t(14;18) mbr in 32% of specimens diagnosed as Hodgkin's disease (HD). In an attempt to confirm and extend those observations the authors used PCR to assay for both the mbr and mcr in HD specimens diagnosed at their institution and examined the specimens for Bcl-2 overproduction. The authors subjected the DNAs from 28 well-characterized HD tumors of 26 patients to PCR analyses using primers specific for the t(14;18) mbr and mcr breakpoints. Based on various PCR controls, the authors ascertained that 26 of the 28 specimens contained amplifiable template DNA. Southern blotting of the amplification products showed that none of the 26 HD DNAs had detectable t(14;18) mbr or mcr breakpoints. By admixing small amounts of t(14;18)-bearing NHL DNA with HD DNA samples, the authors directly demonstrated that the sensitivity of the PCR assays was adequate for the molecular detection of t(14;18)-bearing cells at a frequency comparable to that of Reed-Sternberg cells and their variants in HD. Immunohistochemical studies employing a highly specific anti-Bcl-2 antiserum under conditions optimized to detect t(14;18)-mediated overexpression of the Bcl-2 gene showed that the Reed-Sternberg cells and variants in all 19 HD tumors examined were negative for Bcl-2 immunostaining. In conclusion, the PCR and immunohistochemical data provided evidence that the t(14;18) translocation was not involved in the pathogenesis of the HD cases.
Chromosomes, Human, Pair 18↗
Carcinosarcoma of bladder following long-term cyclophosphamide therapy.
Since the advent of long-term cyclophosphamide therapy, an association between this agent and the subsequent development of bladder neoplasms has been documented. Only six sarcomas have been reported, to our knowledge. This report describes the first case in which a leiomyosarcoma and an invasive transitional cell carcinoma (ie, carcinosarcoma) developed in a patient with non-Hodgkin's lymphoma treated with 240 g of cyclophosphamide over a 6.5-year period.
Carcinosarcoma↗
Proliferation markers Ki-67 and p105 in soft-tissue lesions. Correlation with DNA flow cytometric characteristics.
Frozen tissue immunoreactivity with Ki-67, a monoclonal antibody that recognizes a nuclear antigen in nonresting or proliferating cells, was compared to DNA flow cytometry results (from fresh tissue) in a diverse group of 60 soft-tissue lesions. Both DNA index and Ki-67 score were independently reported to be associated with grade and prognosis in sarcomas, but no direct comparison of these two variables was made. It was attempted to measure proliferative activity in fixed paraffin-embedded tissues immunohistochemically in a subset of lesions using an antibody to another nuclear proliferation antigen, p105. Lesions were given a grade according to lesion category (reactive, 1; benign, 2; low-grade malignant, 3; and high-grade malignant, 4). Ki-67 reactivity correlated relatively well with this grading system (r = 0.59); benign lesions usually exhibited a low Ki-67 score and malignant lesions usually but not always exhibited a high score. For example, some malignant fibrous histiocytomas contained only rare positive cells. Some disparity between Ki-67 score and grade and within histologic types indicates some independence from these features, a fact that may be important when correlation with prognosis is performed. However Ki-67 did not correlate well with flow data such as percentage S phase (r = 0.30), percentage S + G2M phases (r = 0.37), or DNA index (r = 0.39). This probably is due to the fact that Ki-67 also marks cells in the G1 phase, whereas these are excluded in flow data analyses. Anti-p105 highlighted almost all nuclei in all cases tested, including fibromatosis, and did not correlate with Ki-67 score, histologic grade or DNA flow cytometric data. Results with p105 could not be favorably affected by titration experiments. It is reasonable to conclude that the Ki-67 score is a variable related to but independent of histologic grade, histologic type, and DNA flow values. Whether it is prognostically important in human sarcomas, as has been suggested, awaits further clinicopathologic study.
Antigens, Surface↗
Pathologic analysis of advanced adult soft tissue sarcomas, bone sarcomas, and mesotheliomas. The Eastern Cooperative Oncology Group (ECOG) experience.
A total of 488 tumors entered in the Eastern Cooperative Oncology Group (ECOG) Study EST 3377 were evaluated histologically by a panel of pathologists from member institutions for quality control purposes. The overall agreement rate between the eligible submitting diagnosis and the pathology review panel's diagnosis was 74% (312/424). In 10% (44/424), the case was excluded because it was deemed to be nonsarcoma. In the other 16%, the disagreement concerned the type of sarcoma. The histologic type with the lowest agreement rate was rhabdomyosarcoma (17%), followed by sarcoma not otherwise specified (NOS) (27%), angiosarcoma (33%), and fibrosarcoma (48%). These figures reflect the significant degree of difficulty in the diagnosis of these tumor types. The treatment response rate of soft tissue sarcomas in the randomized study of Adriamycin (Adria Laboratories, Columbus, OH) regimens was slightly higher for those with lower grade sarcomas, i.e., 25% (four of 16) response rate for Grade 1 lesions; 22% (17/77) for Grade 2, and 21% (35/170) for Grade 3. When adjusted for type of sarcoma, there was no noticeable difference between Grade 1-2 versus 3 in response rate. A statistically significant difference in the percentage of complete responders was noted between Group A tumors (synovial sarcoma, hemangiopericytoma, sarcoma NOS, and Ewing's; 12.2%) versus Group B tumors (all other types--mostly spindle cell sarcomas; 3.5%) (P = 0.02).
Adolescent↗
Chondroid chordoma: a low-grade chondrosarcoma and its differential diagnosis.
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Bone Neoplasms↗
Gastric small lymphocytic proliferation with immunoglobulin gene rearrangement in pseudolymphoma versus lymphoma.
The nature of gastric infiltrates consisting primarily of benign-appearing small lymphocytes is at present a controversial issue. Earlier reports of gastric lymphoma developing in gastric pseudolymphoma and more recent immunohistochemical studies demonstrating monoclonal B-cell populations in pseudolymphoma suggest that at least some cases represent low-grade lymphomas or clonal precursor lesions that may develop into lymphoma. Observations of a small lymphocytic infiltrate arising in the region of a gastric ulcer that lacked definitive morphologic evidence of malignancy (lymphoma) but was clearly a monoclonal B-cell proliferation by immunohistochemical and gene rearrangement studies support the notion that some gastric lymphoproliferative lesions that histologically have been called pseudolymphomas may include one or more clonal lymphoid expansions. A histopathologic/molecular model suggesting a potential pathway for the development of morphologically recognizable lymphoma from benign-appearing small lymphocytic infiltrates is presented, and the concept that for a variety of lymphoid proliferations clonality and malignancy may not be synonymous is discussed.
Aged↗
A detailed immunohistochemical analysis of cerebellar hemangioblastoma: an undifferentiated mesenchymal tumor.
We studied 23 cases of capillary hemangioblastoma (CHB) of the cerebellum with 17 immunohistochemical cell markers in an attempt to define the nature of the so-called "stromal" cells. These cases were compared to four cases of intracranial metastatic renal cell carcinoma (RCC), which may mimic CHB histologically. The 17 markers studied included vimentin (VIM), Factor VIII-related antigen (FVIIIR:Ag), blood group antigens A, B, and H, Ulex I lectin (Ulex), Alkaline Phosphatase (Alk P), neurofilament protein (NF), glial fibrillary acidic protein (GFAP), S-100 protein (S-100), nerve growth factor receptor (NGFR), muscle-specific actin (MSA), desmin (Des), monoclonal keratin (MKER, including Cam 5.2 and AE1/3), epithelial membrane antigen (EMA), and chromogranin (Chrom). No significant stromal cell staining was seen by markers for endothelial, epithelial, chromaffin, or smooth muscle origin. In some cases individual cells demonstrated positivity for GFAP (4/22) and S-100 protein (13/23); these cells were generally stellate and located near the periphery, and we conclude that these were the result of entrapment of surrounding cerebellum. No case demonstrated NF in stromal cells. However, nearly all cases of CHB showed stromal cell staining with VIM (19/22). In contrast, all of the cases of RCC showed significant staining for at least one marker of epithelial origin (3/4 for MKER and 4/4 for EMA). We conclude that the stromal cell of CHB is neither endothelial, neural, epithelial, pericytic, nor neuroendocrine in origin, and is instead of undifferentiated mesenchymal origin. The designation of this tumor as an "hemangioblastoma," although a misnomer, is firmly established in the literature and should probably be retained.
Actins↗
Expression of growth factors and growth factor receptors in soft tissue tumors. Implications for the autocrine hypothesis.
According to the autocrine hypothesis of cell growth, tumors, in contrast to normal tissue, might simultaneously express both a growth factor and its receptor, resulting in autoregulation and autostimulation of growth. In a related hypothesis, expression of either a growth factor or receptor might allow a tumor to escape exogenous controls on growth, and thereby correlate with malignant potential. Using immunohistochemistry, we investigated these hypotheses in 69 human soft tissue tumors (STT) by assaying for the expression of nerve growth factor and receptor, epidermal growth factor and receptor and platelet-derived growth factor. Both benign (B) and malignant (M) STT expressed a variety of factors and receptors. However, the frequency of any growth factor expression (90% M versus 55% B, p = 0.002) and of multiple factors (59% M versus 24% B, p = 0.006) was significantly greater in malignant tumors. Similarly, expression of any growth factor receptor (73% M versus 31% B, p = 0.001) and of multiple receptors (35% M versus 3% B, p = 0.002) was significantly more frequent in malignant STT. In terms of the autocrine hypothesis, growth factor/receptor co-expression was significantly more common in malignant STT (63% M versus 17% B, p = 0.0002). We conclude that (a) expression of both single and multiple growth factors and receptors was significantly more frequent in malignant STT; (b) support for an autocrine growth mechanism through simultaneous factor/receptor co-expression can be found in both benign and malignant STT; (c) co-expression, however, was more frequent in the malignant tumors; and (d) overall, growth factor and receptor expression, as well as co-expression, was related to biologic potential among human soft tissue tumors.
Epidermal Growth Factor↗
Cortical versus medullary thymomas: a useful morphologic distinction?
We have tested the hypothesis that thymomas can be classified solely on the basis of epithelial cell morphology and that this distinction is prognostically useful. One hundred thymic epithelial tumors were classified according to the morphologic resemblance to cortical or medullary thymic epithelium and to the traditional classification (lymphocytic, epithelial, mixed, and spindled). Follow-up data was obtained on 78 patients. Fifty-eight percent of the tumors were invasive. Nineteen of the invasive tumors relapsed and none of the non-invasive tumors relapsed (P less than .0001). Four of nine tumors with microscopic invasion through the capsule recurred. Statistical analysis showed no significant differences in relapse-free survival for any of the histologic categories. Ninety-four percent of the tumors studied were keratin positive and all were chromogranin negative. Carcinoembryonic antigen was negative for all but one cytologically malignant tumor; of the tumors 75% were epithelial membrane antigen positive, 80% were Leu-7 positive, and 11% were neuron specific enolase positive. Seven of 12 tumors tested expressed HLA-DR. There was no correlation between immunoreactivity and classification. The morphologic cortical/medullary distinction is conceptually attractive but appears clinically to be no more advantageous than the traditional classification.
Adult↗