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Pleomorphic reticulum cell sarcoma, monoclonal gammopathy and amyloidosis: an immunoperoxidase study.

Pleomorphic reticulum cell sarcoma, a histologic variant of the histiocytic lymphomas, presented as an abdominal mass in a 52-year-old woman. Extensive amyloid deposition was present within the tumor mass and an M-component (IgG Lambda) was identified in the serum. Direct immunoperoxidase staining of tissue sections demonstrated the same monoclonal immunoglobulin to be present within the neoplastic cells, presumptive evidence of their ability to both synthesize and secrete immunoglobulin. The presence of amyloid within this patient was probably the direct result of the tissue deposition of this monoclonal immunoglobulin and may be related to the amyloidogenic nature of Lambda light chains. Immunoglobulin production is a specific property of the B lymphocyte series. Transforming B lymphocytes and their differentiating progeny are engaged in active immunoglobulin synthesis and thus may be distinguished from morphologically identical but functionally distinct cells. The demonstration of cytoplasmic monoclonal immunoglobulin within these "malignant reticulum cells" strongly supports the assertion that at least some "histiocytic lymphomas" are neoplastic analogues of transformed B lymphocytes, and are not derived from phagocytic histiocytes, as previously believed.

Amyloidosis↗

Spindle-cell and pleomorphic neoplasms of the skin. A clinicopathologic and immunohistochemical study of 30 cases, with emphasis on "atypical fibroxanthomas".

Atypical fibroxanthoma belongs to the family of spindle-cell and pleomorphic neoplasms of the skin. The lineage of differentiation of this tumor and the means whereby it can be diagnostically separated from other similar morphologic entities have been controversial. In order to address these issues, the authors studied 30 spindle-cell and/or pleomorphic cutaneous tumors, including atypical fibroxanthomas (AFXs), superficial malignant fibrous histiocytomas (MFHs), dermatofibrosarcoma protuberans (DFSPs), sarcomatoid squamous-cell carcinomas (SCCs), spindle-cell malignant melanomas (MMs), and leiomyosarcomas, (LMSs). These cases were analyzed using a panel of eight antibodies and the immunoperoxidase technique. AFXs were reactive for vimentin, alpha-1-antichymotrypsin (AACT), alpha-1-antitrypsin (AAT), and cathepsin-B (CB) but failed to display cytokeratin (CK), epithelial membrane antigen (EMA), S-100 protein, and desmin. MFHs and DFSPs exhibited immunophenotypic profiles that were nearly identical to that just described. In contrast, SCCs were typified by positivity for CK and EMA; MMs exhibited uniform reactivity for S-100 protein; and LMSs contained desmin in four of five cases. A surprising result was the expression of S-100 by LMSs. Also, all tumors displayed at least one of the three proteolytic enzymes assessed in this study (AAT, AACT, and CB), demonstrating the relative diagnostic nonspecificity of these determinants. It is concluded that AFXs are "fibrohistiocytic" neoplasms, with substantial morphologic and immunohistochemical similarity to MFHs. The immunohistochemical classification of spindle-cell and pleomorphic tumors of the skin necessitates the use of antibody panels to assess the presence of markers that are characteristic of each diagnostic group.

Adolescent↗

High-grade pleomorphic T cell lymphoma with restricted involvement of skin and bone marrow.

Pleomorphic T cell lymphoma of the medium to large cell type expressing CD30 antigen is a most aggressive peripheral T cell lymphoma. Currently, there is no satisfactory treatment available for this neoplasm. We report the case of a woman with prominent skin and bone marrow involvement without detectable lymph node localization. This unusual presentation of disease responded well to polychemotherapy combined with autologous bone marrow transplantation.

Antineoplastic Combined Chemotherapy Protocols↗

Quantitation and localization of cycling tumor cells in pleomorphic adenomas and myoepitheliomas: an immunohistochemical analysis.

Previous investigations have suggested that in certain salivary gland tumors only nonluminal (myoepithelial-like) tumor cells proliferate and that this may have histogenetic implications; however, no quantitative assessment of the cycling component is available. We decided, therefore, to enumerate the cycling luminal and nonluminal cells in 15 pleomorphic adenomas and six myoepitheliomas by using an antibody to proliferating cell nuclear antigen. The mean percentages of cycling luminal and nonluminal cells in pleomorphic adenomas were 2.3 +/- 1.4 and 2.4 +/- 2.3, respectively, and 2.1 +/- 0.7 of the tumor cells in myoepitheliomas. Even though duct-like structures in pleomorphic adenomas are considerably separated by more numerous nonluminal cells and, therefore, cycling cells may seem fewer, both cell types proliferate at similar rates. The results indicate that nonluminal cells are not the sole proliferative component in salivary gland tumors.

3,3'-Diaminobenzidine↗

The relative endogenous expression levels of the IFNAR2 isoforms influence the cytostatic and pro-apoptotic effect of IFNalpha on pleomorphic sarcoma cells.

Based on our previous studies where we found that IFNAR2-1, the short IFNalpha/beta receptor variant, was expressed in pleomorphic sarcoma cells, we decided to determine the relative levels of expression of IFNAR2.1 versus the longer form, named IFNAR2.2, in different pleomorphic sarcoma cells in relation to their response to interferon alpha treatment. When examining a panel of PS cells isolated from surgical specimens, we found that IFNAR2.1 prevailed in 6 out 7 lines analysed and that these generally showed cell cycle arrest and low levels of apoptosis upon IFNalpha treatment. The reverse ratio, i.e. higher constitutive levels of IFNAR2.2 than IFNAR2.1, was associated with an irreversible inhibition of cell growth and pronounced apoptosis. Impairment of tumour growth by low- and high-dose IFNalpha treatment of nude mice inoculated with PS cells expressing predominantly IFNAR2.1 further asserted the effect of the cytokine also in vivo. A proteomic analysis of 120 signalling components in growth arrested, apoptotic PS cells harbouring higher levels of IFNAR2.2 revealed engagement of the canonical Jak/Stat/ISGF3-pathway, the activation of the mitochodrial apoptotic pathway and a potentially novel mechanism of cell cycle blockade unrelated to down-regulation of cyclin A/B and their interacting/regulating kinases. Our results confirm the dominant negative role of IFNAR2.1, but also suggest that the relative endogenous levels of the two IFNalpha/beta receptor isoforms may dictate the signalling pathways triggered by the ligand, such as to cause exclusively cell cycle arrest or induce programmed cell death. This parameter may be of importance for the clinical outcome of IFNalpha treatment of PS.

Animals↗

Cytologic findings with histologic correlation in 43 cases of mammary intraductal adenocarcinoma diagnosed by aspiration biopsy.

OBJECTIVE: To review the cytologic and subsequent histologic findings in intraductal mammary adenocarcinoma (ductal adenocarcinoma in situ) (DCIS) to evaluate the role of aspiration biopsy (AB) in identifying and grading the disease. STUDY DESIGN: AB smears and tissue sections from 43 women with pure DCIS who underwent preoperative AB were reviewed. Smears were assessed for cellularity, cellular arrangement (including dissociation, nuclear size and pleomorphism), and presence of nucleoli and necrosis. RESULTS: Of the 43 cases, 22 were high grade (HG) DCIS, 7 cases were intermediate grade (IG), and 14 cases were low grade (LG). Cytologic findings of HG DCIS was as follows: high cellularity (22/22), clusters of pleomorphic cells with large nuclei and increased nuclear/cytoplasmic ratios (22/22), single cells (20/22), prominent nucleoli (22/22) and necrosis (diffuse in 15/22, focal in 7/22). All LG cases had moderately to highly cellular smears with cohesive, 3-dimensional sheets of uniform, small cells with inconspicuous nucleoli arranged around a central lumen, forming "punched-out" spaces. Single cells were prominent in 2 of 14 cases. IG DCIS showed intermediate features between LG and HG DCIS: 3-dimensional sheets with punched-out spaces, abundant single cells, moderate pleomorphism and focal necrosis. CONCLUSION: HG DCIS is easily identifiable on AB smears; however, distinction from invasive carcinoma may not be possible. The cytologic diagnosis of LG DCIS is difficult, and 50% of our cases were called atypical on AB. Recognition of cohesive cellular arrangements with crowding and punched-out spaces is crucial as single cells and prominent atypia are often lacking.

Adult↗

In vitro induction of osteosarcomalike lesion by transformation of differentiating skeletal precursor cells with FBR murine osteosarcoma virus.

This study analyzed the transforming potential of murine viruses in organ cultures of mouse fetal condylar cartilage: Finkel-Biskis-Jinkins-Murine sarcoma virus (FBJ-MuSV) and Finkel-Biskis-Reilly-Murine sarcoma virus (FBR-MuSV). It was only the FBR-MuSV isolated from a radiation-induced osteosarcoma, that induced morphological changes as early as 24 hours following the infection. The latter manifested itself by a marked enlargement of the number of progenitor cells concomitant with an accumulation of spindle-like cells, giant cells, and pleomorphic cells along with large bone spicules and heavy mineralization of the remaining cartilage. The newly formed tissue synthesized type I collagen and revealed profound invasive characteristics. By day 7, FBR-MuSV-infected cultures acquired the appearance of an osteosarcomatouslike lesion. Electron microscopy examinations revealed that both the matrix and the osteogenic cells in the induced tumors differed markedly from that encountered in normal mammalian osseous tissue. To determine which cells within the condylar tissue served as the target for the FBR-MuSV, we used antibodies against viral P30 protein for an indirect immunoperoxidase reaction. The chondroprogenitor cells were the only ones that reacted positively for the virus-specific protein. Further, the in vitro-induced tumor was tumorigenic in syngeneic mice, hence, brought about the development of osteo-fibrosarcoma subcutaneously. By contrast to FBR-MuSV, the FBJ-MuSV did not elicit similar transformative effects in vitro. Since both viruses possess the fos oncogene, it has been suggested that the unique tumorigenic potential of the FBR-MuSV may be linked to structural alterations in the fos oncogene product.

Animals↗

Effects of leukemogenic retroviruses on condylar cartilage in vitro: an ultrastructural study.

Mandibular condyles of late embryonic NMRI mice were used in an in vitro organ culture system to study the effect of bone tumor-derived murine leukemia viruses OS-5 MuLV and OA MuLV known to induce osteopetrosis and osteomas. Skeletal precursor cells present in the condylar tissue normally undergo rapid differentiation in vitro which results in new bone formation. The infection of condyles with either OS-5 MuLV or OA MuLV markedly interfered with the normal developmental pattern of the organ leading to the formation of an atypical, heavily mineralized tissue. Many spindlelike cells and pleomorphic cells were encountered, whereas fibroblastlike cells were found to penetrate an underlying collagen substratum. These observations indicate that bone tumor-inducing leukemogenic retroviruses directly affect cartilage and/or bone precursor cells resulting in pathologic developments in the skeleton.

Animals↗

Soft tissue telangiectatic osteosarcoma in a young patient: imaging and immunostains.

Telangiectatic osteosarcoma of the soft tissue is rare and generally affects adults older than 50 years of age. We present the case of a 17-year-old male who developed a mass in the right thigh. The CT and MRI findings suggested a malignant hemorrhagic tumor without discernable osteoid matrix. Differential diagnosis included various hemorrhagic mesenchymal tumors. Histology revealed large multiple cysts lined with septae and filled with numerous giant cells, pleomorphic spindle cells, and occasionally an osteoid-like substance. Immunostaining for osteocalcin was positive in the cytoplasm of both stromal mononucleate and multinucleate giant cells. Surgery and adjuvant chemotherapy were applied and the patient survives to the time of writing after 30 months of follow-up without recurrence or metastasis.

Adolescent↗

Metastasis to the orbit from transitional cell carcinoma of the bladder.

PURPOSE: To demonstrate the pathological features of the extremely rare metastatic transitional cell carcinoma (TCC) from the bladder to the orbit, and to review the literature on metastatic TCC to the orbit. METHODS: A 74-year-old man experienced 2 weeks of red eye, proptosis, diplopia, pain, and visual loss in the right eye. Three years previous to the current presentation, the patient had undergone a transurethral resection for superficial and moderately differentiated TCC of the bladder. A transseptal anterior orbitotomy was performed. RESULTS: Histopathological examination of the orbital lesion revealed nests of carcinomatous cells. Atypical pleomorphic cells with vacuolated cytoplasm were evident. The cellular morphology of the orbital lesion was identical to that of the primary TCC. There have been 12 previously reported cases of metastases to the orbit from TCC of the bladder, with the time from onset of primary TCC to observation of ocular symptoms ranging from 3 weeks to 11 years. Mean survival after orbital metastasis developed from TCC was 3.0 months. CONCLUSION: This study presents a detailed description of the pathological features of metastatic TCC in the orbit. In cases of orbital metastasis from TCC, patient prognosis is very poor.

Aged↗

Phenotypic and functional characterization of HTLV positive neoplastic T cells cultured with interleukin-2--I. Retention of morphology, phenotype and selective cytotoxic properties in long term culture.

T cells from the peripheral blood of a T-cell chronic lymphocytic leukemia (T-CLL) patient, cultured in the presence of interleukin-2 (IL-2), were found to express the p19 structural core protein of the human T-cell leukemia/lymphoma virus (HTLV) and to release type C virus particles. Comparison of the T-CLL cell line with the original leukemic T cells revealed that both the fresh and the proliferating T-CLL cells were pleomorphic cells that showed a convoluted nucleus and formed rosettes with sheep erythrocytes (E-rosettes). They were reactive with the monoclonal antibodies OKT1, OKT4 and OKT11, but not with OKT3, OKT6 or OKT8, indicating that they were mature T cells but that they differed from normal T cells in their lack of reactivity with OKT3. In addition they did not bind peanut agglutinin or OKM-1, and were negative for Epstein-Barr nuclear antigen, surface immunoglobulin, non-specific esterase activity of Fc- or complement receptors. Part of the fresh T-CLL cells reacted with a monoclonal antibody recognizing HLA-DR antigens (p29, 34) (36%) and with anti-Tac (62%), a monoclonal antibody directed at the IL-2 receptor, indicating that the T-CLL cells were partially activated already in vivo. After culture in vitro all proliferating T-CLL cells expressed HLA-DR and Tac antigens. The fresh T-CLL cells were found to be defective in cell-mediated lympholysis (CML) generated in mixed lymphocyte culture (MLC), antibody-dependent cellular cytotoxicity (ADCC) and lectin-dependent cellular cytotoxicity (LDCC). In addition they failed to exhibit natural killer (NK) cell activity against targets that are usually very susceptible to lysis, such as K562, but were able to kill two tumor-derived cell lines, the melanoma NKI-4 and the neuroblastoma CHP-100. The same pattern of selective killing was observed using the proliferating T-CLL cells as effectors, or cloned T-CLL cultures obtained from them by limiting dilution procedures. Therefore, it was concluded that the T-CLL cells represented a clonal expansion of neoplastic T cells that retained their phenotype and cytotoxic properties after culture in vitro.

Antibody-Dependent Cell Cytotoxicity↗

Immunohistochemical and genetic analysis of osteoclastic giant cell tumor of the pancreas.

Clinical, histopathologic, immunohistochemical, and genetic analyses of 2 osteoclastic giant cell tumors of the pancreas are presented. The neoplasms were composed of osteoclastic giant cells and pleomorphic cells (PCs). The tissue-specific markers gave evidence of mesenchymal nature of the osteoclastic giant cells, as well as other components of the tumor, and lacked any signs of epithelial differentiation in both patients. The nonepithelial nature of both components in the osteoclastic giant cell tumors presented may be associated with a better prognosis, which corresponds to the previous reports of similar neoplasms. A positive immunoreactivity to neuron-specific enolase was recorded in patient 2. The presence of CD68 in osteoclastic giant cells proved their histiocytic nature. Both components of the tumors showed a negative immunoreactivity to desmin and only a scattered reactivity to smooth muscle cell actin, typical markers of myofibroblastic differentiation. Mutation analysis of the tumor revealed the wild state of both p53 and K-ras oncogenes in both patients. A positive immunoreactivity for p53 in PCs of both osteoclastic giant cell tumors was recorded, whereas osteoclastic giant cells did not express this protein. The expression of p21 was recorded in osteoclastic giant cells in patient 1. The absence of Ki-67 in the osteoclastic giant cells and its expression in PCs gave evidence of a different proliferation rate of both cell populations. Different tissue-specific markers, a different proliferation rate, and a different state of oncogene activation in the osteoclastic giant cell tumors contribute to the idea that the tumor derives from a pluripotent cell that may differentiate into an array of phenotypes.

Adult↗

Cytopathological expression of different types of urothelial carcinoma in situ in urinary bladder washings.

OBJECTIVE: To evaluate and compare the cytopathological expression of the five major histological types of carcinoma in situ (CIS) in urinary bladder washings from patients with flat urothelial lesions. MATERIALS AND METHODS: Seventy-five cases of primary and secondary urothelial CIS with no concomitant tumours, and having tissue and cytological samples, were identified. Biopsies were evaluated based on the consensus classification as: large-cell pleomorphic; large-cell non-pleomorphic; small-cell; clinging; and cancerization of the urothelium. In the cytological classification the 'clinging' category was excluded, as its definition depends on the histological appearance. kappa statistics were used to evaluate the correlation between histopathology and cytology. RESULTS: More than one subtype of CIS could often be identified in both the histological and cytological specimens. Cytology often showed more subtypes than did histopathology. Statistically, there was only a moderate correlation between histopathology and cytology for recognising different patterns. CONCLUSION: Different patterns of CIS can be identified by cytology; it is important for cytologists to be aware of the cytological spectrum of CIS and not to under-diagnose monomorphic, pagetoid (cancerization) and small-cell forms. Studies on treatments for CIS and of the clinical significance of different subtypes of CIS should include both cytopathology and histopathology.

Aged↗

Cytopathologic and clinicopathologic features of ovarian hepatoid carcinoma. A case report.

BACKGROUND: Hepatoid carcinoma is a rare ovarian tumor and is thought to be a different histopathologic subtype from hepatoid-type yolk sac tumor based upon its pathologic features. However, the cytopathologic characteristics of ovarian hepatoid carcinoma (OHC) have not been reported previously. We report the clinicopathologic and cytopathologic features and immunoreactivity of a case of OHC. CASE: A 36-year-old woman presented to our department with lower abdominal pain. A left ovarian tumor was found on pelvic examination, magnetic resonance imaging and computed tomography. The tumor was diagnosed as a hepatoid carcinoma of the left ovary based upon the histopathology of the surgically resected specimen. Cytopathologic specimens from a tumor touch preparation of the tumor exhibited pleomorphic tumor cells with abundant cytoplasm. The nuclei contained rough, granular chromatin and large, prominent nucleoli. Several tumor cells were multinucleated. Tumor cells were immunoreactive for alpha-fetoprotein (AFP). Hematoxylin and eosin staining revealed that the tumor cells were in a sinusoidal pattern resembling hepatocellular carcinoma without any glandular formation. The tumor cells were negative for human chorionic gonadotropin while positive for AFP, alpha-1-antitripsin, CA-125 and carcinoembryonic antigen. CONCLUSION: Cytopathologic examination is of considerable aid in the diagnosis of OHC since cytopathologic preparations highlight the characteristic cell pleomorphism.

Adult↗

Soft tissue giant cell tumor of low malignant potential: a proposal for the reclassification of malignant giant cell tumor of soft parts.

Although "giant cell tumor of soft parts" has traditionally been considered a single entity as reflected in the original term "malignant giant cell tumor of soft parts (MGCT)" and later by the term "malignant fibrous histiocytoma, giant cell type" the degree of atypia and mitotic activity varies in this group, suggesting biologic heterogeneity. The clinicopathologic features of 31 tumors meeting the traditional criteria of MGCT but having only mild to moderate nuclear atypia are presented. Patients with these tumors (19 females; 12 males) ranged in age from 14 to 84 years (mean, 40 years) and presented with masses of involving either superficial (n = 16) or deep (n = 13) soft tissue. Most occurred on the arm or hand (n = 16) and ranged in size from 0.7 to 6.5 cm (mean, 2.1 cm). The tumors consisted of sheets and nodules of rounded mononuclear cells that blended with spindled cells and benign osteoclastic giant cells. Pleomorphic giant cells were absent. Osteoid was noted in 10 cases, but features typically associated with tenosynovial giant cell tumors (such as dense stromal hyaline, siderophages, and xanthoma cells) were nearly always absent. Mitotic figures ranged from 1-10/10 HPF (mean, 2-3/10 high-powered field), and angiolymphatic invasion was present in 10 cases. Necrosis was absent, however. The mononuclear cells expressed CD68, tartrate-resistant acid phosphatase, and smooth muscle actin, but lacked CD45, S100 protein, desmin, and lysozyme, an immunophenotypic profile identical to that of giant cell tumor of bone. Follow-up information in 19 patients (mean, 3 yrs; median, 1-7 yrs) indicated recurrences in four patients, but none developed metastasis. This behavior contrasts significantly with the high-grade behavior traditionally associated with MGCT of soft parts. These giant cell tumors can be consistently recognized by the lack of cytologic atypia even in the face of mitotic activity and vascular invasion. Although their long term metastatic risk is not fully defined, we propose they be termed "giant cell tumors of low malignant potential" and regarded as the soft tissue analogue of giant cell tumor of bone. The term "malignant giant cell tumor of soft parts" or giant cell malignant fibrous histiocytoma should be restricted to histologically high-grade lesions.

Acid Phosphatase↗

Morphology and in vivo growth characteristics of an atypical murine proliferative osseous lesion induced in vitro.

Mandibular condyles of late embryonic NMRI mice were used to study the effect of the FBR murine osteosarcoma virus in an in vitro tissue culture system. Chondroprogenitor cells and chondroblastic cells present in the condylar tissue normally undergo rapid differentiation in vitro which results in an advanced stage of bone formation. The infection of condyles with FBR murine osteosarcoma virus induced the transformation of bone progenitor cells and the formation of an atypical proliferative osseous lesion. In markedly disorganized tissue many spindle-like cells, giant cells, and pleomorphic cells were seen together with the formation of large bone spicules and the heavy mineralization of osteoid-like material and of the remaining cartilage. Fibroblast-like cells were found to penetrate from the perichondrial zone into the condylar mass and also into the underlying collagen sponge. The in vivo growth characteristics of FBR murine osteosarcoma virus-infected condyles after 3 days in culture were studied via s.c. transplantation into syngeneic mice. Control condyles developed normal trabecular bone, whereas the infected condyles induced a strong cellular response with the presence of atypical cells and newly formed connective tissue and bone in situ. These observations raise the possibility of a novel approach for further investigations related to numerous aspects of virus-induced osteosarcomagenesis.

Animals↗

Metastatic malignant fibrous histiocytoma in lung examined by fine needle aspiration: case report and literature review.

Malignant fibrous histiocytoma appears to be emerging as one of the most common soft tissue sarcomas of late adult life. Cytologic features of a metastatic malignant fibrous histiocytoma in the lung, examined by fine needle aspiration, are reported. Essentially, four cell types in various proportions were observed: spindled cells, pleomorphic giant cells, undifferentiated mesenchymal-type cells and rare signet ring "lipoblast-like" cells. There also were several huge hyperchromatic and often bizarre naked nuclei.

Aged↗

[Granular cell tumor of the rectum: description of a case with unusual histological features].

The localization of granular cell tumor to the rectum is rare. We describe a case characterized by areas with spindle cell pattern, pleomorphic cells with acidophilic granular cytoplasm, nuclear variations and absence of mitoses. Diagnosis has been confirmed by immunohistochemical study. After 22-month follow-up the patient does not show evidence of recurrence or metastases.

Biomarkers, Tumor↗