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Lipid rich rhabdomyosarcoma.

A lipid rich rhabdomyosarcoma of the paratesticular region was studied by light microscopy, histochemistry, immunohistochemistry and electron microscopy. The tumour was composed of primitive looking, vacuolated, and pleomorphic cells. Lipid was present in varying amounts in all cells but was especially abundant in the vacuolated and pleomorphic cells. Some cells showed eosinophilic fibrillary cytoplasm but cross-striations were not seen. Tumour cells were positive for desmin, muscle specific actin, and vimentin. A few cells were myoglobin positive. At electron microscopy, the presence of lipid was confirmed, while thick and thin filaments, Z disks, lamina and glycogen were observed, thereby confirming striated muscle differentiation. Although moderate amounts of lipid can be expected in almost any tumour, lipid rich rhabdomyosarcomas have received little attention. The present report provides a comprehensively examined case of such a tumour initially presenting diagnostic difficulty because of its possible confusion with liposarcoma.

Adult↗

Unscheduled DNA synthesis in cells of different shape in fibroblast cultures from donors of various ages.

Human fibroblast cultures derived from normal donors of different ages were examined for the proportion of spindle-shaped, sail-shaped, and large pleomorphic cells which constitute the cultures, and the capacities of these cells for unscheduled DNA synthesis (UDS). The large pleomorphic cells were most abundant in all cultures, followed in abundance by the sail-shaped and spindle-shaped cells. Major changes in the occurrence of the cells of different shape with increased donor age were not apparent, although the abundance of spindle-shaped cells decreased slightly with donor age. The large pleomorphic and sail-shaped cells exhibited similar UDS which was consistently greater than that of the spindle-shaped cells. No major changes in UDS were observed for either type of cell with increased donor age.

Adult↗

Interleukin-6/soluble interleukin-6 receptor signaling attenuates proliferation and invasion, and induces morphological changes of a newly established pleomorphic malignant fibrous histiocytoma cell line.

Pleomorphic malignant fibrous histiocytoma (MFH) is occasionally associated with inflammatory paraneoplastic syndrome (PNS). Recently, we reported that interleukin (IL)-6, one of the candidate cytokines, which induces such systemic inflammatory reaction, may be a tumor-associated factor involved in the pathogenesis and its clinical manifestations of MFH. In the local microenvironment, tumor-induced inflammatory reaction may play a role favoring tumor progression. To clarify the biological relevance of IL-6 in MFH, we established a human MFH cell line, named MIPS-2, derived from a resected specimen of a patient presenting with PNS. In this patient, the serum IL-6 level ran parallel to the disease course: elevated serum IL-6 concentration normalized immediately after radical surgery, and re-elevation occurred on tumor recurrence. MIPS-2 presented pleomorphic appearance, severe nuclear abnormalities with prominent nucleoli, and tumorigenesis in nude mice. MIPS-2 expressed IL-6, IL-6 receptor (IL-6R), and glycoprotein 130 (gp130) but lacked the soluble form of IL-6R (sIL-6R), as determined by flow cytometry and reverse transcriptase-polymerase chain reaction analyses. Stimulation of MIPS-2 with IL-6 combined with exogenous sIL-6R induced phosphorylation of both signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK), decreased cell proliferation, attenuated invasion, and induced morphological changes. Collectively, these data suggested that the IL-6/sIL-6R signaling pathway plays a pivotal role for proliferation, invasion, and morphology of MFH via STAT3 and MAPK pathway as autocrine and/or paracrine manner, and proposed the therapeutic potential for the use of both anti-growth factor and proinflammatory cytokine-targeting strategies to combat devastating MFH.

Adult↗

Usefulness of argyrophilic nucleolar organizer staining for histologic grading of soft-tissue sarcomas.

Accurate histologic grading is essential for making a proper therapy decision in soft-tissue sarcomas (STS). The usefulness of the argyrophilic stain for nucleolar organizer region (AgNOR) in assessing the histologic grade of STS has been examined. One hundred and forty-two patients with STS confined to the extremity and trunk were selected. Tumors were classified based on the criteria of Enzinger and Weiss ["Soft-Tissue Tumors." St. Louis: C. V. Mosby, 1983]. In addition, non-specific classification was made based on the shape of proliferating cells occupying more than 50% of the field in the sections such as pleomorphic cell, small round cell, spindle cell, epithelioid cell, myxoid, and unclassified tumors. The mean number of AgNOR dots per nucleus of tumor cells was calculated in 200 cells (AgNOR count). Each category of non-specific classification was divided into a high-count group (< 8 AgNOR count) and a low-count group (> 8 NOR). The low-count group showed a significantly better prognosis than the high-count group in small round cell and spindle cell tumors (P < 0.007 and P < 0.0005, respectively). Similar results were obtained in pleomorphic cell tumors, though they were statistically not significant because of the relatively small number of examined cases. Most patients with epithelioid cell and myxoid tumors were in the low-count group. These findings suggest that the assessment of histologic grading of STS could be made effectively by the non-specific classification and the aid of AgNOR staining.

Actuarial Analysis↗

Sjögren's syndrome with specific cutaneous manifestations and multifocal clonal T-cell populations progressing to a cutaneous pleomorphic T-cell lymphoma.

A case is presented of primary Sjögren's syndrome of the parotid gland with specific skin manifestations, consisting of diffuse lymphoid infiltrates with proliferative and metaplastic changes of sweat glands, a histologic picture similar to that seen in the parotid gland. Material of the parotid gland, a submandibular lymph node showing expanded T-cell areas, and several skin biopsies were studied immunohistologically for the presence of clonal B-cell populations. Because of a polyclonal kappa/lambda pattern of the B-lymphocytes, the possibility of a B-cell non-Hodgkin's lymphoma (NHL) was excluded. The initially morphologically benign lymphocytic skin infiltrates (1985) changed into a pleomorphic T-cell lymphoma (1987). Southern blot analysis of the atypical skin infiltrates and of the original material of the parotid gland and submandibular lymph node revealed identical clonal rearrangements of the T-cell receptor B-chain. Rearrangement of Ig genes was not found.

Aged↗

Fine-needle aspiration cytology of pleomorphic hyalinized angiectatic tumor: A case report.

Pleomorphic hyalinized angiectatic tumor (PHAT) of soft parts is a neoplasm characterized by spindle and pleomorphic cells associated with an angiectatic vasculature. We describe the cytological findings of a fine-needle aspiration biopsy (FNAB) from the right medial knee of a 45-yr-old woman. The aspirate material was entirely submitted in Cytolit solution. The specimen was moderately cellular and was comprised of spindle cells in a background of fibrinous material. The cells varied from small, bland spindle cells with a fine chromatin pattern and inconspicuous nucleoli to larger pleomorphic cells with coarser chromatin and occasional intranuclear inclusions. Most of the cells were arranged singly with sporadic small cluster formation with indistinct cell borders. Rare mononuclear inflammatory cells morphologically compatible with mast cells were identified. The differential diagnosis include solitary fibrous tumor (SFT) and ancient schwannoma, which also shows fibrous-like material and spindle cells that may have intranuclear inclusions.

Biopsy, Fine-Needle↗

"Hyaline cells" in pleomorphic adenoma of salivary gland origin.

Fifty-two cases of pleomorphic adenoma of minor salivary gland origin and seventy-two cases of pleomorphic adenoma of major salivary gland origin were examined for the presence of hyaline cells (plasmacytoid cells). Hyaline cells were found in 38 percent of the minor salivary gland cases and 21 percent of the major salivary gland cases. When stained with hematoxylin and eosin, the hyaline cells exhibited an eccentric nucleus and a striking homogenous, ground-glass, eosinophilic cytoplasm. At the ultrastructural level, the cytoplasm of the hyaline cells was closely packed with intermediate-sized filaments having no apparent orientation. It is suggested that the hyaline cells are modified myoepithelial cells.

Adenoma, Pleomorphic↗

Killer cell immunoglobulin-like receptor expression delineates in situ Sézary syndrome lymphocytes.

p140/KIR3DL2 has been identified in malignant cell lines isolated from the skin and blood of patients with transformed mycosis fungoides (MF) and Sézary's syndrome (SS). For the first time, the expression of a cell membrane structure appeared to be able to distinguish CD4+ tumour lymphocytes from reactive lymphocytes in these small cutaneous T-cell lymphomas (CTCLs). This study has examined the in vivo expression of this receptor in various CTCL subtypes, which constituted a heterogeneous group. Tumour cells diffusely expressed KIR in SS, in lymphomatoid papulosis (LyP) and in CD4+CD30+ as well as CD8+ large cell pleomorphic CTCL. In contrast, the infiltrating lymphocytes did not express KIR in MF at the patch/plaque stage or in CD4+CD30- large cell pleomorphic CTCL, except for scattered small cells. One quarter of the transformed MF tested exhibited KIR+ tumour cells, suggesting heterogeneity in this subtype. KIR expression was also examined in inflammatory lesions characterized by a dense infiltrate of T cells, such as lupus erythematosus and lichen planus. Only scattered CD8+ cells in lichen planus expressed a significant amount of KIR3DL2. Taken together, these results show for the first time that KIR molecules are expressed in distinct subtypes of malignant CTCL. It is also shown for the first time that SS and MF, which are frequent variants of CTCL with similar histological features, can be distinguished by their KIR3DL2 expression analysis. The identification of this KIR also differentiates between lupus erythematosus and lichen planus, which are both diseases with dense benign lymphocytic infiltrates.

Antibodies, Monoclonal↗

Cytological diagnosis of primary leiomyosarcoma of bone: case report.

We report on a case of primary leiomyosarcoma of the bone in a 77-yr-old man. The patient presented with a painful, enlarging mass in the left shoulder of 6 mo duration. Radiography and computed tomography (CT) revealed a large destructive intramedullary lesion of the proximal humerus, with massive extension into the surrounding soft tissues. CT-guided fine-needle aspiration biopsies (FNAB) of both the bony and soft-tissue lesions were performed. Cytological examination showed a neoplastic process composed of spindle cells mixed with pleomorphic cells. The smooth muscle origin of the neoplastic cells was confirmed by immunocytochemical analysis. We describe the cytological features of this rare primary tumor of bone, and consider the differential diagnosis of spindle-cell neoplasms.

Aged↗

Establishment and characterization of cell lines derived from a transplantable rat malignant meningioma: morphological heterogeneity and production of nerve growth factor.

A cell line (KMY-J) was established from a transplantable tumor (MM-KMY) derived from a spontaneous malignant meningioma arising in an aged F344 rat, and three cloned cell lines (KMY-1, KMY-2 and KMY-3) were induced from the parent KMY-J. Morphologically, KMY-J and tumors induced in syngeneic rats by KMY-J showed cell pleomorphism. All neoplastic cells in KMY-J and its tumors were immunoreactive to vimentin; occasional cells reacted to ED1 (rat macrophage/histiocyte-specific antibody) and alpha-smooth muscle actin (alpha-SMA), indicating expression of histiocytic or myofibroblastic immunophenotypes of meningioma cells. In contrast, KMY-1, KMY-2 and KMY-3 consisted of a uniform cell population differing from each other. KMY-1-induced tumors were similar histologically to meningeal fibrosarcomas. Dendritic cells seen in KMY-2 cultures gave an appearance of arachnoid trabecular cells. In KMY-3 and its tumors, large round cells and multinucleated giant cells were predominant. Cells of these cloned cell lines also reacted to vimentin, but were negative for ED1 and alpha-SMA. By the bioassay using PC12 cells and reverse transcription-polymerase chain reaction for nerve growth factor (NGF) mRNA, production of NGF was demonstrated in the parent and cloned cell lines. The present cell lines may prove useful for studying the histological features of meningeal tumors and the bioactive factors produced by meningeal cells.

Animals↗

Immunohistochemical markers for prognosis of cerebral glioblastomas.

Glioblastoma is the commonest neuroectodermal tumor and the most malignant in the range of cerebral astrocytic gliomas. The prognostic utility of various biological markers for glioblastomas has been broadly tested but the results obtained are regarded as controversial. In the present study, 302 glioblastoma specimens were studied to evaluate a possible association between clinical outcome and expression of some immunohistochemical variables. Furthermore, tumors examined were subdivided on the three cytological subsets--small-cell (SGB), pleomorphic-cell (PGB) and gemistocytic (GGB). Immunohistochemical variables differed between various subsets: the number of p53-positive tumors was found to be prevailed among the PGB, whereas the number of tumors with EGFR and mdm2 positivity was significantly greater in SGB. GGB contained significantly lowest mean proliferating cell nuclear antigen (PCNA) labeling index (LI), greater number of p21ras positive cases, and higher mean apoptotic index (AI). Survival time in patients with SGB, EGFR and mdm2-positivity and PCNA LI >40% was found to be significantly shorter, whereas presence of p21ras and AI >0.5% were associated with prolonged survival. Multivariate analysis revealed that survival time is associated with SGB, EGFR-positivity, and AI (p = 0.0023, p = 0.0035 and p = 0.0029 respectively). We conclude that although some immunohistochemical variables were found to be significant for glioblastoma outcome, they appear to be closely related to biology of single cytological subsets. Furthermore, these variables exhibited no prognostic value when they were analyzed within each cytological subset separately. Therefore, the glioblastoma subdivision on three cytological subsets proposed by us is carrying some element of rationality but, undoubtedly, requires further prospective studies.

Adult↗

Detection of circulating MN/CA9 positive renal cell carcinoma cells during operation.

Our previous study demonstrated the clear detection of MN/CA9 mRNA in peripheral blood samples from RCC patients. However, approximately 30 % of control blood samples from healthy volunteers showed MN/CA9 expression. We have developed a new primer set and optimized the PCR conditions, now resulting in a specificity of 100 %. In tissue samples, all clear cell type carcinomas but none of the spindle cell type and pleomorphic cell type tumors expressed the MN/CA9 message. Analysis of MN/CA9 messages in peripheral blood samples from RCC patients gave positive results for 0/2, 1/9, 0/4 and 4/12 of stage I, II, III and IV cases, respectively. RT-PCR analysis using preoperative renal venous blood samples resulted in clear detection of MN/CA9 positive cells in 2/4, 3/13, 2/6 and 1/1 of stage I, II, III and IV cases, respectively. Our results suggest that assessment of MN/CA9 expression by RT-PCR is a promising method for detecting cancer cells in the circulation of patients with RCC.

Adult↗

[Space-occupying lesion of the pancreas--how frequently not due to a suspected ductal adenocarcinoma?].

In patients with a space-occupying lesion of the pancreas at first a primary ductal adenocarcinoma is considered as the cause. Other tumours or metastases are assumed to occur very rarely. Therapy and prognosis of other pancreas tumours differ from therapy and prognosis of a primary ductal adenocarcinoma. We therefore examined the question of how frequently a space-occupying lesion of the pancreas was not due to a ductal adenocarcinoma in our case materials. Retrospectively 70 patients who had undergone a percutaneous puncture of a space-occupying mass of the pancreas under ultrasonographic control were included in the study (34 women, 36 men). In 62 patients a clear histological diagnosis was possible on the basis of the biopsy. In 53 cases (76 %) a primary adenocarcinoma of the pancreas could be diagnosed. In 5 patients (7 %) these masses turned out to be metastases of a previously known malignant tumour disease (2 x mammary carcinoma, 2 x gastric carcinoma, 1 x sigmoid carcinoma). Other tumours could be detected in 4 cases (6 %) including a tuberculoma, an endocrine tumour, a fusocellular sarcoma with partial neurogenic differentiation and a large-cell and pleomorphic-cell anaplastic, partly sarcomatoid carcinoma. In patients with a space-occupying lesion of the pancreas, tumours other than a ductal adenocarcinoma are not rare. In particular, in cases of a previously known malignant tumour disease a space-occupying lesion of the pancreas can also turn out to be a metastasis. Every other individual tumour entity is rare. Other tumour entities at large, however, are found in daily routine. The preoperative biopsy of space-occupying lesions of the pancreas, therefore, still has a clinical importance for the further therapy planning.

Aged↗

Fine-needle aspiration biopsy of soft tissue sarcomas. A cytomorphologic analysis with emphasis on histologic subtyping, grading, and therapeutic significance.

Because therapy for sarcoma often incorporates histologic subtype, grade, stage, and anatomic location, establishing a specific histologic subtype often is essential. To evaluate the effectiveness of fine-needle aspiration biopsy (FNAB) in histologic subtyping of soft tissue sarcomas, we retrospectively reviewed 73 consecutive aspirates from 67 patients, none of whom had a previously established sarcoma diagnosis. Sarcoma cases were subgrouped according to predominant cytomorphologic features: pleomorphic cell, 19; small round cell, 18; spindle cell, 18; myxoid, 10; epithelioid/polygonal cell, 7; 1 case of well-differentiated liposarcoma was analyzed separately. Ancillary studies were used for 25 cases. Among adequate specimens, 61 tumors were recognized as sarcoma. A specific and accurate histologic subtype was determined in 34 cases. Ancillary studies were most useful for histologic subtyping of small round cell and spindle cell sarcomas. Myxoid sarcomas were subtyped easily based solely on histomorphologic features. Pleomorphic cell and epithelioid/polygonal cell sarcomas were recognized easily as malignant but difficult to subtype by FNAB. With the exception of small round cell sarcomas, histologic subtyping of a sarcoma usually did not directly influence therapy. With meticulous attention to clinicopathologic features and ancillary techniques, many sarcomas, especially small round cell, spindle cell, and myxoid types, may be subtyped successfully by FNAB, within limitations.

Adolescent↗

Primary mucosal melanomas of the nasal cavity and paranasal sinuses. A clinicopathological analysis of 14 cases.

We present 14 patients with primary sinonasal melanomas (SM) identified from 1984-1997 in our archives (11/14 lateral nose, 1/14 nasal septum, 2/14 paranasal sinuses; 8M/6F, mean age 67.7 years, range 39-88 years). Survival was poor (median 9 months) with death related to extensive local disease and/or widespread hematogenous metastases. The following histological subtypes were identified in descending order: amelanotic small blue cell, pleomorphic, epithelioid, spindle cell and myxoid. High mitotic rate and vascular invasion, absence of tumor-infiltrating lymphocytes and regression were features shared by all SM. Negative staining of B- and T-cell markers, LCA, neuroendocrine markers such as NSE, chromogranin and synaptophysin, and CK-negativity excluded olfactory neuroblastoma, small cell undifferentiated carcinoma, and lymphoma. S-100 protein was expressed in all SM, but demonstrated variable staining intensity with areas of complete negativity. HMB45 was strongly and uniformly (>80%) expressed in all undifferentiated small blue cell SM. The pigmented SM were predominantly HMB45-negative. The strong HMB45 staining in amelanotic small blue cell SM is explained by the reaction of HMB45 antibody with an oncofetal antigen found in immature melanosomes. In these poorly differentiated amelanotic malignant melanomas, antibody to HMB45 proved to be a superb diagnostic marker. We therefore strongly advocate the inclusion of HMB45 antibody in the panel of antibodies for initial work-up of undifferentiated mucosal neoplasms, since a negative S-100 stain in small biopsy material may result in incorrect classification of these neoplasms.

Adult↗

Anaplastic thyroid carcinoma in fine needle aspirates.

OBJECTIVE: To analyze the diagnostic problems with fine needle aspiration biopsy in anaplastic thyroid carcinoma (ATC) and to describe the cytomorphologic characteristics in 113 cases. STUDY DESIGN: A retrospective analysis of 113 fine needle aspirates and 67 surgical specimens from 113 patients with ATC admitted to the Institute of Oncology, Ljubljana, in 1972-1992. RESULTS: In a series of 113 fine needle aspirates of ATC, 3 (2.7%) were inadequate, 3 (2.7%) suboptimal and 107 (94.7%) diagnostic of malignancy. On reexamination, 96/107 (89.7%) were diagnosed as ATC, 6 (5.6%) as differentiated thyroid carcinoma, and 5 (4.6%) as a malignant tumor not otherwise specified. As to the predominant cell population, fine needle aspirates showed three different cell patterns: (1) pleomorphic cell (43 cases), (2) round cell (33 cases), and (3) spindle cell pattern (7 cases). In the present retrospective analysis we identified three main reasons for inadequate or nonrepresentative fine needle aspiration biopsy sampling: (1) tumor regressive changes (necrosis, hemorrhage, leukocytic infiltration), (2) extensive tumor fibrosis, and (3) distinct differentiated and anaplastic patterns in the same tumor. CONCLUSIONS: The major diagnostic problem with fine needle aspiration biopsy (FNAB) of ATC is related to sample quality. Cytomorphologic features of ATC are highly specific and easy to recognize. Due to the simple technique and high diagnostic accuracy, FNAB is the method of choice in patients with ATC.

Adult↗

Giant cell tumor of soft parts. A report of an equine and a feline case.

Masses removed from the superficial fascia of the jugular groove of a 12-year-old Arabian mare and from the femoral canal of a 7 1/2-year-old female cat appeared to be counterparts of the human malignant giant cell tumor of soft parts, even recapitulating the clinical behavior of the respective subgroups. Histologically, both neoplasms contained the characteristic features of the malignant giant cell tumor of soft parts: large multinucleate giant cells, pleomorphic mononuclear giant cells, histiocytes, fibroblasts and fibrocytes that were sometimes sarcomatous, and foci of hemorrhage and necrosis. Ultrastructural characteristics of the giant cells suggest mesenchymal origin with osteoblastic or chondroblastic differentiation.

Animals↗

Pure choriocarcinoma of testis with tumor-infiltrating lymphocytes and granulomas.

Pure choriocarcinoma is very rare in the testes, and host immune responses including tumor infiltrating lymphocytes are unusual in choriocarcinoma. This study reports a case of pure testicular choriocarcinoma with extensive lymphocytic infiltrate and granulomatous inflammation. Scrotal ultrasonography revealed a heterogeneous, hyperechoic intratesticular mass. -human chorionic gonadotropin levels were elevated in a radioimmunoassay. The hemorrhagic and necrotic solid mass was composed of two cell populations - mononuclear pleomorphic cells and intimately admixed multinucleated smudged cells. The tumor cells were positive for cytokeratin 7, epidermal growth factor receptors, human placental lactogen and p57. Many inflammatory cells were present within the tumor. The majority of infiltrating cells were CD8-positive cytotoxic cells, which also expressed granzyme-B and TIA-1. The tumor cells were positive for FasL, but negative for Fas. Therefore, this case seemed to escape the host defense response to the tumor due to the loss of Fas, although the cellular host immune response was still active.

Adult↗