Malignant fibrous histiocytoma,giant cell type,of the breast mimicking metaplastic carcinoma. A case report

BACKGROUND: We report a case of malignant fibrous histiocytoma, giant cell type (MFHGC), of the breast. A review of the literature failed to reveal cytology-based reports on this entity. The cytologic similarity of breast MFHGC on fine needle aspiration biopsy (FNAB) to other malignant breast neoplasms, including carcinoma with osteoclastlike giant cells, metaplastic carcinoma and breast sarcomas, as well as benign reactive processes, makes the recognition of this tumor challenging. CASE: A 72-year-old woman presented with a 5-month history of an enlarging breast mass. FNAB of the mass showed a hypercellular smear composed of cohesive, branching clusters of spindle cells with ovoid, focally hyperchromatic nuclei and inconspicuous nucleoli. Interspersed osteoclastlike giant cells, some associated with clusters of spindle cells, were uniformly seen throughout the smear. The background was hemorrhagic, with cellular debris and occasional spindle cells and lymphocytes. No ductal epithelial or myoepithelial cells were seen. An incisional biopsy was performed, followed by radical mastectomy. The histologic examination was diagnostic of MFHGC. The diagnosis was supported by immunohistochemical and electron microscopic studies. CONCLUSION: MFHGC, also called primary giant cell tumor of soft tissues, is composed of a mixture of histiocytes, fibroblasts and bland-appearing osteoclastlike giant cells with a multinodular growth pattern. Although MFHGC rarely occurs in the breast and the definitive diagnosis is difficult based on cytology alone, the diagnosis can be considered when a cytologic examination reveals a hypercellular, spindle cell smear with osteoclastlike giant cells in the absence of ductal epithelial or myoepithelial cells.     

Spindle cell and cartilaginous metaplasia in a breast carcinoma with osteoclastlike stromal cells. A difficult fine needle aspiration diagnosis

The cytologic picture in fine needle aspirates from a unique type of breast tumor, with stromal proliferation of osteoclastlike giant cells, cartilaginous metaplasia and metaplastic spindle-shaped carcinomatous cells, is described. In this case, an erroneous cytologic diagnosis of fat necrosis associated with a rich component of reactive fibroblasts was made. This false-negative report, which was mainly due to lack of an obvious carcinomatous component in the aspirated material, is discussed with emphasis placed on the need to exclude spindle cell metaplasia in a breast carcinoma whose aspirates are characterized by a rich component of spindle-shaped cells.     

Osteoclastomalike giant cell tumor of the parotid gland: report of a case with fine needle aspiration diagnosis

BACKGROUND: Osteoclastomalike giant cell tumor of the parotid gland has been reported rarely. The tumor has occurred rarely at many sites, such as thyroid, pancreas, soft tissue, breast, skin, heart, colon, lung, kidney, ovary and bladder. The exact origin of the tumor is unclear. However, osteoclastlike giant cells have been considered either part of a stromal process reactive to a neoplasm or a component of a primary neoplasm. CASE: A 35-year-old female presented with a mass in the left parotid gland clinically diagnosed as a pleomorphic adenoma. Fine needle aspiration (FNA) was advised before surgical excision. FNA smears revealed numerous osteoclastlike, multinucleated giant cells and many malignant-looking mononuclear cells. The smears were diagnosed as positive for malignancy, suggestive of osteoclastomalike giant cell tumor. The tumor was excised, and histopathologic study confirmed the cytologic diagnosis. CONCLUSION: The cytologic findings of osteoclastomalike giant cell tumor of the parotid gland have not been previously reported. FNA aided the diagnosis and planning of treatment. FNA is important in the diagnosis of parotid tumors.     

Fine needle aspiration cytology of invasive cribriform carcinoma of the breast with osteoclastlike giant cells: a case report

BACKGROUND: Nonneoplastic osteoclastlike giant cells are occasionally associated with carcinoma of the breast, pancreatobiliary and gastrointestinal systems. In the breast, this uncommon stromal response is seen mainly in invasive carcinoma with low grade cytology, among which invasive cribriform carcinoma is the classic example. Details of the fine needle aspiration cytology of this phenomenon, especially in thin-layer preparations, have been described rarely. CASE: The fine needle aspiration cytology of an invasive cribriform carcinoma of the breast occurred in a 66-year-old woman. Cytology showed cohesive sheets and three-dimensional cribriform clusters of bland-looking and mitotically inactive ductal cells in a blood-stained background. Scattered multinucleated, osteoclastlike giant cells, some containing hemosiderin granules, were also seen. Myoepithelial cells and naked nuclei were not obvious. The cellular composition was more discernible in liquid-based cytologic preparations. Histologic examination of the excisional biopsy showed an invasive cribriform carcinoma associated with many osteoclastlike giant cells in a hypervascular stroma. CONCLUSION: In view of the extremely low grade cytology of the malignant ductal cells, invasive cribriform carcinoma may closely mimic benign proliferative breast diseases on fine needle aspiration biopsy. Recognition of this special relationship with osteoclastlike giant cells, which are rarely present in certain subtypes of breast cancer but not benign lesions, can help to arrive at a correct cytologic diagnosis.     

Bronchoscopic cytology of metastatic breast carcinoma with osteoclastlike giant cells

The cytologic appearance of bronchoscopic washings and brushings is reported in a rare case of pulmonary metastasis from breast carcinoma with osteoclastlike giant cells.     

Immunocytochemical and ultrastructural study of the rare osteoclast-type carcinoma of the breast in a fine needle aspirate

The cytologic findings in a fine needle aspirate from a case of the rare osteoclastlike carcinoma of the breast are described along with the immunocytochemical and ultrastructural findings. The ultrastructural and immunocytochemical findings suggest that the osteoclastlike giant cells in this type of carcinoma are not of epithelial origin, but rather are reactive and of a histiocytic-stromal origin.     

Mixed osteoclastic/pleomorphic giant cell tumor of the pancreas: a case report

BACKGROUND: Mixed giant cell tumor (MGCT) of the pancreas is a rare malignant neoplasm. The tumor contains pleomorphic giant cells (PGC), pleomorphic mononuclear cells (PMC) and osteoclastic giant cells (OGC). We describe the first fine needle aspiration biopsy (FNAB) diagnosis of this tumor. CASE: A 76-year-old woman was discovered (on imaging studies) to have an apparently inoperable mass in the head of the pancreas. Computed tomography-guided FNAB showed a malignant neoplasm with features of an MGCT. PGC/PMC, OGC and spindle cells were present. The PGC/PMC expressed epithelial antigens, pancytokeratin, CAM 5.2, AE1/AE3 and epithelial membrane antigen (EMA). The spindle cells focally stained for EMA. OGC were negative for the epithelial antigens. OGC, PGC/PMC and the spindle cells were positive for the mesenchymal marker vimentin. CONCLUSION: FNAB was instrumental in making the diagnosis of a rare pancreatic tumor, MGCT. Immunocytochemistry was helpful in making a definitive diagnosis and suggested that MGCT is a carcinosarcoma like neoplasm. The morphology and immunocytochemical profile raise the possibility that osteoclastic giant cell tumor and pleomorphic giant cell tumor may be different morphologic and biologic expressions of the same tumor.     

Primary giant cell tumor of soft tissue. Report of a case with fine needle aspiration cytologic and histologic findings

BACKGROUND: So-called primary giant cell tumor of soft tissue of low malignant potential is the rare soft tissue analogue of giant cell tumor of bone, occurring primarily in superficial soft tissue. To our knowledge, the cytologic findings in bulky giant cell tumor of deep soft tissue were described only once, and no further report on the subcutaneous giant cell tumor could be retrieved from the literature. CASE: A 58-year-old woman presented with a well-demarcated, 1.5-cm-diameter dermal tumor. Fine needle aspiration smears contained numerous osteoclastlike giant cells and mononuclear cells showing bland and vesicular nuclei. A small fragment of branching vasculature and 1 mitosis were found. Those cytologic findings were enough to suggest a diagnosis of giant cell tumor of soft tissue, confirmed as a deep dermal giant cell on surgical resection. CONCLUSION: Primary giant cell tumor of soft tissue of low malignant potential should be considered in the differential diagnosis of bland-looking giant cell-rich lesions. Awareness of its existence and knowledge of its cytologic features are important for a correct preoperative cytologic diagnosis.     

Fine needle aspiration of pleomorphic giant-cell carcinoma of the pancreas. Case report with ultrastructural observations

The fine needle aspirate in a case of pleomorphic giant-cell carcinoma of the pancreas, an unusual but highly malignant variant of ductal carcinoma of the pancreas, was characterized by bizarre tumor giant cells, "osteoclastlike" giant cells and abundant mitoses. The differential diagnostic possibilities include sarcoma (rhabdomyosarcoma, malignant fibrous histiocytoma and liposarcoma), melanoma, choriocarcinoma, metastatic giant-cell carcinoma of the lung and giant-cell tumor of the pancreas. A combination of clinical history, imaging findings and fine needle aspiration biopsy with transmission electron microscopy could lead to the appropriate diagnosis and help differentiate this entity from the other possible considerations.     

Stage specific effects of carbendazim (MBC) on meiotic cell cycle progression in mouse oocytes

The effects of the pesticide carbendazim (MBC) on the in vitro meiotic maturation of mouse oocytes were evaluated using conventional and confocal fluorescence microscopy. The response of oocytes exposed to 0, 3, 10, or 30 μM MBC during meiotic maturation was analyzed with respect to chromosome organization, meiotic spindle microtubules, and cortical actin using fluorescent labels for each of these structures. Continuous exposure to MBC during the resumption of meiosis resulted in a dose-dependent inhibition of meiotic cell cycle progression at metaphase of meiosis-1. Drug exposure at the metaphase-anaphase transition of meiosis-1 did not interfere with cell cycle progression to metaphase-2 except at high concentrations (30 μM). At the level of spindle microtubule organization, MBC caused a loss of nonacetylated microtubules and a decrease in spindle size at 3 or 10 μM concentrations. Thirty μM MBC prevented spindle assembly when added at the beginning of meiotic maturation or caused spindle pole disruption and fragmentation when added to preformed spindles. Spindle disruption involved a loss of phosphoprotein epitopes, as monitored by MPM-2 staining, and resulted in the appearance of dispersed chromosomes that retained a metaphase-plate location on spindle fragments associated with the oocyte cortex. Polar body extrusion was impaired by MBC, and abnormal polar bodies were observed in most treated oocytes. The results suggest that MBC disrupts cell cycle progression in mouse oocytes by altering meiotic spindle microtubule stability and spindle pole integrity. Mol. Reprod. Dev. 46:351–362, 1997. © 1997 Wiley-Liss, Inc.     

Leiomyosarcoma of the breast: report of a case with fine needle aspiration cytologic, histologic and immunohistochemical features

BACKGROUND: Leiomyosarcoma of the breast is a rare neoplasm. We present a case of primary leiomyosarcoma of the breast in a middle-aged female in whom fine needle aspiration cytologic features suggested sarcoma. CASE: A 55-year-old female presented with a rapidly growing breast lump of 1 month's duration. On examination, an ulcerating, 12 x 10 cm tumor was seen involving the lower medial and lateral quadrants of the right breast. Fine needle aspiration cytology showed variably sized, dissociated and loosely clustered polygonal, plump and spindle cells with pale blue cytoplasm and vesicular nuclei that were round, oval or irregular. Occasional giant forms and nucleolated and mitotic cells were present. A single cluster of benign ductal cells was seen. The tumor cells did not express immunocytologic reactivity to estrogen receptor protein. A cytologic diagnosis of sarcoma was given with differential diagnoses of metaplastic carcinoma and malignant phyllodes tumor. Histologic study established the diagnosis of leiomyosarcoma. Leiomyosarcoma of the breast shows fine needle aspiration cytologic features of sarcoma, but specific tumor typing may not be possible, especially when the cytologic material is inadequate for ancillary staining required to distinguish leiomyosarcoma from metaplastic carcinoma and malignant phyllodes tumor.     

Fine needle aspiration cytology of mammary carcinoma with choriocarcinomatous features: a report of 2 cases

BACKGROUND: Neoplasms of the breast containing multinucleated giant cells (MGCs) include both benign and malignant entities, such as benign soft tissue giant cell tumors, atypical fibrous histiocytoma, sarcomas, metaplastic carcinomas and the uncommon carcinomas containing osteoclast-like giant cells (OGC). Breast carcinoma with choriocarcinomatous features (BCCF) is a distinct variant of breast cancer. CASES: We report the cytologic features, pathologic findings and immunohistochemical profile in 2 cases of this unusual variant of breast carcinoma. Two women aged 53 and 50 years women presented with a history of left and right breast lump but no local lymphadenopathy, respectively. Fine needle aspiration cytology (FNAC) of both cases revealed abundant MGC with highly pleomorphic tumor cells in the hemorrhagic necrotic background. Both of the cases were histopathologically diagnosed as BCCF. CONCLUSION: Choriocarcinomatous differentiation with multinucleated syncytiotrophoblast-like giant cells is extremely rare in breast tumors. Although rare, FNAC of breast cancer with pleomorphic MGC requires careful search for differential diagnosis; breast carcinoma with giant cell features (choriocarcinomatous features, OGC features) must be differentiated from metastatic tumors and other breast lesions containing giant cells.     

Cytoplasmic microtubules and fungal morphogenesis: ultrastructural effects of methyl benzimidazole-2-ylcarbamate determined by freeze- substitution of hyphal tip cells

The effects of methyl benzimidazole-2-ylcarbamate (MBC), one of only a few agents that are active against microtubules of fungi, were analyzed at the ultrastructural level in freeze-substituted hyphal tip cells of Fusarium acuminatum. Nontreated and control cells had numerous microtubules throughout. After just 10 min of exposure to MBC, almost no cytoplasmic microtubules were present, except near spindle pole bodies. After 45 min of exposure to MBC, no microtubules were present in hyphal tip cells, but they were present in the relatively quiescent subapical cells. These observations suggested that there are different rates of turnover for cytoplasmic microtubules in apical and subapical cells and for microtubules near spindle pole bodies and that MBC acts by inhibiting microtubules assembly. A statistical analysis of the distribution of intracytoplasmic vesicles in thick sections of cells treated with MBC, D2O or MBC + D2O was obtained by use of a high- voltage electron microscope. More than 50% of the vesicles in the apical 30 micrometers of control cells were found to lie within 2 micrometers of the tip cell apex. MBC treatment caused this vesicle distribution to become uniform, resulting in a substantial increase in the number of vesicles in subapical regions. The reduction in the number of cytoplasmic microtubules, induced by MBC, apparently inhibited intracellular transport of these vesicles and rendered random the longitudinal orientation of mitochondria. In most cases, D2O appeared capable of preventing these MBC-effects through stabilization of microtubules. These observations support the "vesicle hypothesis" of tip growth and establish a transport role for cytoplasmic microtubules in fungal morphogenesis.     

Logistic regression analysis of high grade spindle cell neoplasms. A fine needle aspiration cytologic study.

OBJECTIVE: To identify primary diagnostic cytologic criteria for various high grade spindle cell neoplasms. STUDY DESIGN: We reviewed 30 osteosarcomas, 29 malignant fibrous histiocytomas (MFH), 26 malignant melanomas, 13 chondrosarcomas, 12 leiomyosarcomas, 7 angiosarcomas and 5 liposarcomas. All specimens were coded as to the presence or absence of the following variables: high or low cellularity, tissuelike fragments, glandlike fragments, single cells, binucleated cells, multinucleated cells, lipoblastlike cells, histiocytelike cells, fibroblastlike cells, signet-ring cells, short spindle cells, long filamentous cells, stellate cells, osteoclastic giant cells, malignant giant cells, background cells, pointed nuclei, cigar-shaped nuclei, fishhook-shaped nuclei, round or ovoid nuclei, intranuclear vacuoles, macronucleoli, small nucleoli, mitotic figures, abnormal mitotic figures, pleomorphism, nuclear/cytoplasmic ratio (mild, moderate, marked increase), amount of cytoplasm (scant, moderate, abundant), fine or coarse granular cytoplasm, intracytoplasmic hemosiderin deposits, melanin, cytoplasmic vacuoles, fat, capillary vessel fragments, storiform pattern, necrosis, large or small amount of myxoid material, filamentous stroma, dense collagenous stroma, osteoid, chondroid and cells in lacunae. A logistic regression analysis was performed to identify the variables predictive of each diagnostic category. RESULTS: The statistical analysis selected positive expression of osteoid, osteoclastic giant cells and low cellularity as the primary criteria associated with osteosarcomas. Positive expression of fibroblastlike cells, large amount of myxoid material and multinucleated cells were identified to be the key criteria for MFH. The analysis selected the presence of melanin as the major criterion for malignant melanomas, cells lying in lacunae for chondrosarcomas, fishhook nuclei for leiomyosarcomas, intracytoplasmic iron deposits for angiosarcomas and lipoblastlike cells for liposarcomas. CONCLUSION: From the previously described cytologic criteria, statistical analysis helped identify several key features that are significant in the evaluation of pleomorphic spindle cell neoplasms.     

Chondroblastoma of the rib presenting as an intrathoracic mass. Report of a case with fine needle aspiration biopsy, immunocytochemistry and electron microscopy.

We describe an unusual case of chondroblastoma of the rib, initially presenting as a mediastinal mass eroding a vertebra, in which the preoperative diagnosis was made by fine needle aspiration (FNA) cytology and confirmed by histology and electron microscopy of the surgical specimen. Cytologic study of the smears revealed osteoclastlike giant cells and dishesive, mononucleate tumor cells; sections of the paraffin-embedded, aspirated material showed the chondroid matrix and typical chicken wire calcific deposits. Supporting diagnostic evidence was provided by immunohistochemical demonstration of S-100 protein. Unusual features were the presence of intranuclear pseudoinclusions and cytoplasmic granular deposits, which proved to contain iron on histochemical staining, ultrastructural morphology and x-ray analysis. This case emphasizes the value of FNA cytology in providing a correct diagnosis of chondroblastoma as well as the utility of embedding the aspirated material for histologic, immunohistochemical and ultrastructural studies.     

Malignant melanoma of mediastinum misdiagnosed as a spindle cell thymoma in a fine needle aspirate: a case report

BACKGROUND: Malignant melanomas in the medastinum are extremely rare. Both primary melanomas and metastatic lesions from a primary elsewhere can occur in the mediastinum. Aspiration biopsy of a melanoma at this unusual site may pose problems in diagnosis. CASE: A 35-year-old woman presented with an anterior mediastinal mass. Cytologic smears were hemorrhaghic and revealed a loosely dispersed population of spindle cells with prominent nucleoli. In view of the location, the possibility of spindle cell thymoma was suggested on cytology. Subsequent histology revealed a malignant melanoma. CONCLUSION: This case stresses that the cytopathologist should keep in mind the remote differential diagnosis of a malignant melanoma while evaluating spindle cell neoplasms of the mediastinum, especially in tumors with prominent cell dispersal and with cells that have prominent nucleoli even without melanin pigment. Accurate diagnosis helps in evaluating patients and avoids unnecessary surgery when the lesion represents a metastasis to the mediastinum from a primary elsewhere.     

Paratesticular spindle cell rhabdomyosarcoma diagnosed by fine needle aspiration cytology: a case report

BACKGROUND: Spindle cell rhabdomyosarcoma is a rare, newly identified subtype ofembryonal rhabdomyosarcoma with improved behavior and a predilection for the paratesticular area. Fine needle aspiration (FNA) cytology findings of embryonal rhabdomyosarcoma have been described. However, there is no previous report on the cytologic findings of spindle cell rhabdomyosarcoma at testicular or extratesticular sites. CASE: A 13-year-old boy presented with a large, right sided scrotal mass. Fine needle aspiration (FNA) was performed for rapid diagnosis. The smears revealed numerous spindle cells and large fragments of cytoplasmic processes with cross-striations and were diagnosed as spindle cell rhabdomyosarcoma. The histologic sections were also diagnosed as spindle cell rhabdomyosarcoma. CONCLUSION: The cytologic findings of this rare tumor have not been reported before. The cross-striations were easily identified in FNA smears, so the diagnosis of spindle cell rhabdomyosarcoma was made confidently. The histologic sections showed only spindle cells with different patterns of arrangement, resembling leiomyosarcoma. The cross-striations were not identified in the histologic sections. In this case cytologic diagnosis aided the histologic diagnosis.     

Insulin-like growth factor-I mediates osteoclast-like cell formation stimulated by parathyroid hormone

There have been several lines of evidence that parathyroid hormone (PTH) stimulates production of insulinlike growth factor I (IGF-I) in bone and that IGF-I stimulates osteoclast formation. Thus, the present study was performed to clarify the possible role of IGF-I in PTH-stimulated osteoclastlike cell formation and the role of PTH-responsive dual signal transduction systems (cyclic [c] AMP-dependent protein kinase [PKA] and calcium/protein kinase C [PKC]) in its mechanism. Treatment with anti-IGF-I antibody (1–10 μg/ml) partially but significantly blocked hPTH-(1-34)-stimulated osteoclastlike cell formation in unfractionated mouse bone cell cultures, although it did not affect osteoclastlike cell formation stimulated by 1,25-dihydroxyvitamin D₃. Rp-cAMPS (10^-4 M), a direct PKA inhibitor, as well as two types of PKC inhibitors, H-7 (10 μM) and staurosporine (3 nM), and dantrolene (10^-5 M), an inhibitor of calcium mobilization from intracellular calcium stores, all significantly blocked PTH-stimulated osteoclastlike cell formation. Anti-IGF-I antibody (3 μg/ml) significantly blocked osteoclastlike cell formation stimulated by 10^-4 M dbcAMP, 10^-4 M Sp-cAMPS, a direct PKA activator, and 10^-5 M forskolin in mouse bone cell cultures. Dibutyryl cAMP, forskolin, and hPTH-(1-34) significantly stimulated mRNA expression of both IGF-I and IGF-binding protein 5 (IGFBP-5) in these cultures, but neither 10^-7 M PMA, a PKC activator, nor 10^-7 M A23187 did. Moreover, anti-IGF-I antibody significantly blocked osteoclastlike cell formation stimulated by the conditioned medium from MC3T3-E1 cells pretreated with 10^-8 PTH-(1-34), which induced IGF-I and IGFBP-5 mRNA expression in these cells. In conclusion, the present study indicates that IGF-I mediates osteoclastlike cell formation stimulated by PTH and that the PKA pathway is involved in its mechanism. However, IGF-I does not seem to be the sole effector molecule to be active in this system. J. Cell. Physiol. 172:55–62, 1997. © 1997 Wiley-Liss, Inc.     

Chromosomes initiate spindle assembly upon experimental dissolution of the nuclear envelope in grasshopper spermatocytes

Chromosomes are known to enhance spindle microtubule assembly in grasshopper spermatocytes, which suggested to us that chromosomes might play an essential role in the initiation of spindle formation. Chromosomes might, for example, activate other spindle components such as centrosomes and tubulin subunits upon the breakdown of the nuclear envelope. We tested this possibility in living grasshopper spermatocytes. We ruptured the nuclear envelope during prophase, which prematurely exposed the centrosomes to chromosomes and nuclear sap. Spindle assembly was promptly initiated. In contrast, assembly of the spindle was completely inhibited if the nucleus was mechanically removed from a late prophase cell. Other experiments showed that the trigger for spindle assembly is associated with the chromosomes; other constituents of the nucleus cannot initiate spindle assembly in the absence of the chromosomes. The initiation of spindle assembly required centrosomes as well as chromosomes. Extracting centrosomes from late prophase cells completely inhibited spindle assembly after dissolution of the nuclear envelope. We conclude that the normal formation of a bipolar spindle in grasshopper spermatocytes is regulated by chromosomes. A possible explanation is an activator, perhaps a chromosomal protein (Yeo, J.-P., F. Alderuccio, and B.-H. Toh. 1994a. Nature (Lond.). 367: 288-291), that promotes and stabilizes the assembly of astral microtubules and thus promotes assembly of the spindle.