Giant cell tumor of bone: Frequent actin immunoreactivity in stromal tumor cells

Although giant cell tumor (GCT) of bone is a well-recognized neoplasm with distinctive clinical and histopathological features, the origin of tumor cells, particularly of mononuclear cells, has not yet been established. An immunohistochemicai study was carried out on 11 cases of GCT of bone to examine the cellular natures of stromal mononuclear cells. In all cases, stromal cells were positive for muscle actin (HHF35) or α-smooth muscle actin, and in eight of 11 cases, positivist was intense and extensive. The cell margin of osteoclast-like giant cells (OGC) was stained positively by muscle actin, In addition to Intense and diffuse positive staining of the cytoplasm for KP1 (CD68), whereas α-smooth muscle acting exhibited a negative reaction on the OGC. In conclusion, the tumor cells with muscle actin and α-smooth muscle actin proclivities are not rare but frequently numerous In the GCT of bone; whereas further observation Is necessary to elucidate whether the stromal cells exhibit myoflbroblastlc cell differentiation exactly.     

Granular cell tumor expressing myogenic markers in the prostate

A granular cell tumor in the prostate of a 72 year old male is reported. The tumor nest was composed of large polygonal tumor cells, possessing cytoplasmlc eoslnophlllc granules which were positive with PAS stain and resistant to diastase digestion. Immunohistochemically, most tumor cells were strongly positive with anti-α-smooth muscle actin and -neuron specific enolase antibodies. Only a few scattered tumor cells were reacted with antt-S-100 protein antibody. These find-Ings might suggest smooth muscle differentiation of this case, and provide an additional Insight into the histogenesis of granular cell tumors, especially In their heterogeneity.     

Actin expression in neural crest cell-derived tumors including schwannomas, malignant peripheral nerve sheath tumors, neurofibromas and melanocytic tumors

Tumors that originate from neural crest-derived cells represent a heterogeneous group of neoplasms including benign and malignant tumors with melanocytic and schwannian differentiation. The immunophenotype of these tumors is well known but little is known about the expression of smooth muscle/myofibroblastic markers in these tumors. A total of 590 neural crest-derived tumors (50 benign schwannomas, five malignant peripheral nerve sheath tumors, 80 neurofibromas, 240 nevocytic nevi, 115 primary melanomas, and 100 melanoma metastases) were studied with respect to α-smooth muscle actin and muscle-specific actin expression. α-Smooth muscle actin and muscle-specific actin-positive tumor cells with a co-expression of S-100 protein were found in one benign schwannoma, one primary cutaneous melanoma, and four melanoma metastases. Four of these cases were examined ultrastructurally, but typical actin filaments with focal densities were not found in any of the four. Other immunohistochemical markers examined including desmin, h-caldesmon and smooth muscle myosin heavy chain were negative in the tumor cells. The present results suggest that neural crest-derived tumors could show expression of α-smooth muscle actin on rare occasion.     

Ossifying fibromyxoid tumor of soft parts: A morphological and immunohistochemical study

A case is presented of ossifying fibromyxoid tumor of soft parts (OFMTSP) which occurred in the left cheek of a 59 year old Chinese woman. Histologically, the tumor was located in the subcutis with a fibrous pseudocapsule that contained discontinuous rims of mature trabecular bone. The tumor cells were small, round to ovoid with a uniform, round nucleus and a pale or slightly eosinophilic cytoplasm. Most of the cells were arranged In a random manner, some in a vague lace-like pattern. Mitotic figures were extremely rare. The stroma appeared fibromyxoid with scattered foci of mucinous lakes. Immunohistochemically, most of the neoplastic cells displayed immunoreactivities for S-100 protein, S-100 protein α, vimentin and α-smooth muscle actin; many tumor cells were positive for desmin. The tumor also showed stromal immunoreactivity for type IV collagen and was negative for cytokeratlns, epithelial membrane antigen, glial fibrillary acidic protein, neurofilaments, muscle-specific actin, Leu-7, myelin-basic protein, osteocalcin and melanoma-specific antigen. The immunophenotypes expressed by the present OFMTSP seem to reflect two lineages of neoplastic cell differentiation, that is of nerve sheath and of smooth muscle; at the present stage, it is premature to diagnose this lesion as either nerve sheath or smooth muscle tumor.     

Extrauterine low-grade endometrial stromal sarcoma: Report of three cases

Three cases of rare low-grade endometrial stromal sarcoma of the extrauterine tissue are presented. Each one occurred In the ovary, pelvic and abdominal cavities. Two were associated with endometriosls. Histologically, the tumors were characterized by an infiltrative and diffuse proliferation of uniform round or oval cells, abundant small vessels, low mitotic activity, the presence of foam cells and vascular Invasion. lmmunohistochemically, all tumors expressed vimentin, muscle markers (desmin, muscle-specific actin and α-smooth muscle actin) and progesterone receptors. Two tumors were diploid and one was aneuploid by flow cytometry. All patients were well with no evidence of disease 16–39 months after surgery. It Is suggested that this neoplasm may arise with or without endometriosis under hormonal Influence. This rare variant of Müllerian tumors should not be confused with adenosarcoma and soft tissue tumors, such as smooth muscle tumors and solitary fibrous tumor.     

Salivary duct carcinoma: A clinicopathologic study of three cases with a review of the literature

Three cases of salivary duct carcinoma are presented. They occurred in a 60 year old man, a 66 year old man and a 57 year old woman. All of the lesions were located In the parotid gland. The tumor size ranged from 3 to 5 cm across the largest diameter. Facial paralysis was observed in two cases. Histologically, intreductal and invasive adenocarcinoma showing papillary, cribriform, and solid patterns with comede like necrosis was observed. lmmunohistochemically, the tumor cells were positive for keratin and epithelial membrane antigen. No myoepithelial cells were demonstrated within the tumor by staining for S-100 protein, α-smooth muscle actin or muscle specific actin. Ultrastncturally, intracytoplasmic lumina with microvilli, a moderate number of mltochrondria, lysosomes, and tight junctions were found. Regional lymph node metastasis was observed in one case, and distant metastasis developed in two cases. All of me patients were treated with adjuvant postoperative irradiation. One patient died of disease at 11 months after the initial diagnosis, another was alive with disease at 8 months, and the third patient was alive without disease at 2 years and 3 months. Salivary duct carcinoma should be ditterentiated from low-grade salivary gland carcinomas using morphologic and clinical criteria because of its poor prognosis even with aggressive therapy.     

Uterine leiomyosarcoma with osteoclast-like giant cells: Histopathological and cytological observations

A 56 year old woman presented with abnormal uterine bleeding. Except for a myomatous uterus, no other abnormalities were noted on physical examination and in radiographic and serologic studies. The hysterectomy specimen revealed an 8 cm uterine fundic tumor composed of two histologically different patterns that merged with one another; one was a well differentiated leiomyosarcoma and the other a mixture of osteoclast-like giant cells (OGC) and plump spindle cells whose cell borders blended, resembling the histology of giant cell tumor of bone. lmmunohistochemical studies showed positive staining for muscle actin, α-smooth muscle actin, and KP-1 (CD68) in both the spindle cells and OGC. The latter also stained for α-1-antitrypsin and α-1-antichy-motrypsln. These findings suggested that OGC may be formed by the fusion of spindle cells of leiomyosarcoma and also express histiocytic markers.     

Ossifying fibromyxoid tumor: Report of a case with cytomorphologic description

Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm with uncertain histogenesis. Most cases behave in a clinically benign fashion; however, a small percentage of tumors may locally recur or metastasize. Herein we present a case of a 56‐year‐old man who presented with an enlarging left groin mass, left inner thigh numbness, burning paresthesia and discomfort in his left groin. The mass sampled by fine‐ needle aspiration and needle core biopsy. Cytology showed bland‐appearing epithelioid cells with round nuclei and fine chromatin, with fragments of fibromyxoid stroma in the background. Immunohistochemical stains performed on the core biopsy showed that the lesional cells were focally positive for S100 protein and negative for desmin, smooth muscle actin, CD34 and cytokeratin AE1/AE3. A benign neoplasm was favored with ossifying fibromyxoid tumor as the main entity in the differential diagnosis. A subsequent resection showed a well‐circumscribed 5 cm mass with firm consistency and focal areas of calcifications. Histologically, the tumor had a nodular growth pattern with relatively bland spindle cells containing round to oval nuclei suspended in a variably collagenous to myxoid stroma. Significant ossification and bone formation was also noted. There was no significant atypia, necrosis or increased mitoses. Ossifying fibromyxoid tumors have distinct cytologic features and should be considered in the differential diagnosis of soft tissue tumors with prominent ossification. Diagn. Cytopathol. 2015;43:646–649. © 2015 Wiley Periodicals, Inc.     

Spindle cell lipoma of the breast.

Spindle cell lesions, which commonly arise in the soft tissues, may present in the breast and be difficult to distinguish from primary mammary spindle cell tumors. We present the case of a 28 year old woman with a 1.5 cm circumscribed spindle cell lipoma lying deep within the tissue of the right breast. Thin, uniform spindle cells were associated with collagen bundles, mature adipocytes and entrapped normal mammary ducts, lobules, vessels and nerves, appearances which simulated an aggressively infiltrating tumor. The spindle cells proved immunoreactive to CD34 and vimentin but non-reactive for cytokeratin, S100, desmin, smooth muscle actin and Factor VIII. Although surgical resection was incomplete, the patient is alive and without evidence of tumor recurrence 12 months postoperatively. In our case, a conservative approach to management was justified and supported by the patient's subsequent clinical course. This case exemplifies the diagnostic challenge of spindle cell lesions arising in breast tissue and the value of immunoperoxidase stains.     

h-Caldesmon as a specific marker for smooth muscle tumors. Comparison with other smooth muscle markers in bone tumors

Caldesmon is a protein widely distributed in smooth and non-smooth muscle cells and is thought to regulate cellular contraction. Its isoform, high-molecular-weight caldesmon (h-CD), was demonstrated to be specific for smooth muscle cells and smooth muscle tumors of the soft tissue and to never be expressed in myofibroblasts. We performed an immunohistochemical study to examine h-CD expression in the following bone tumors: conventional and non-conventional osteosarcoma, 13; malignant fibrous histiocytoma of bone, 5; giant cell tumors of bone, 5; chondroblastoma, 3; metastatic leiomyosarcoma, 2; and rhabdomyosarcoma, 1. Frequent immunoreactivity for muscle actin (alpha-smooth muscle actin or muscle-specific actin) was seen in 11 of 13 osteosarcomas and all other tumors, whereas h-CD was expressed intensely only in 2 leiomyosarcomas. h-CD is considered a specific and useful marker to distinguish smooth muscle tumor from bone tumors with myoid differentiation.     

Ossifying Fibromyxoid Tumor: Modified Myoepithelial Cell Tumor? Report of Three Cases with Immunohistochemical and Electron Microscopic Studies

Ossifying fibromyxoid tumors (OFMT) are rare soft tissue tumors of uncertain histogenesis and clinical behavior. Since Enzinger, Weiss, and Liang first described 59 examples in 1989 (Am Surg Pathol. 13:817–827), approximately 150 cases have been reported. Their clinicopathologic features are fairly well characterized and their histogenesis remains unknown. Three examples of soft tissue tumors with typical histopathologic characteristics of OFMT were studied: case 1, a 43-year-old female with a 2.5-cm tumor of the back; case 2, a 56-year-old man with an 8-cm thigh mass; and case 3, an 81-year-old female with a 13.5-cm buttock tumor. For immunohistochemistry, formalin-fixed, paraffin-embedded tissue sections were stained with antibodies against cytokeratin, smooth muscle actin, desmin, vimentin, S-100 protein, EMA, and collagen type IV using standard ABC-peroxidase methods. For electron microscopy, tissue samples fixed in EM-grade buffered formalin were processed according to routine methods. Immunohistochemistry showed that the tumor cells were positive for vimentin and S-100 protein in all 3 cases. Stains for collagen type IV revealed diffusely positive staining in the stroma with a tendency for stronger staining around the cell borders in 2 out of 3 cases. Desmin was positive in one and actin was positive in one other case. By electron microscopy, tumor cells were characterized by centrally located round to oval nuclei with varying amounts of cytoplasm containing scanty cytoplasmic organelles. There were rare profiles of rough-surfaced endoplasmic reticulum (RER) and rare mitochondria with areas of condensed intermediate filaments. No tonofilaments or actin filaments were present. There were multiple short web-like processes, some of which were attached to that of neighboring cells by primitive cell junctions. In all 3 cases, lesional cells showed external lamina (EL), which was abundant in case 1, forming redundant scrolls frequently. In case 2, EL was less prominent and incomplete, and interrupted portions of EL were present only along the periphery of cell columns or nests bordering the stroma. In case 3, which behaved as a malignant tumor, the tumor cells were less differentiated spindle cells with primitive cellular features, and EL was rarely found along the short span of tumor cell borders. In this study, tumor cells in OFMT were polygonal to stellate often with multiple short cytoplasmic processes. The tumor cells were found to form cell clusters attached by primitive intercellular junctions between cytoplasmic processes forming intercellular bridges. The cell borders facing the stroma around cell clusters tended to be flat and had incomplete EL, while no EL was present along the cell borders facing the inner aspect of cell clusters. These ultrastructural findings together with immunophenotypic expression of S-100 protein presented closer resemblance to those of modified myoepithelial cells in pleomorphic adenomas of salivary glands and skin appendages rather than peripheral nerve sheath tumors. The authors conclude that these findings render more support to the hypothesis of myoepithelial histogenesis of OFMT. They also conclude that ultrastructural study not only helps accurate diagnosis, but also may aid in predicting malignant behavior by the degree of deviation from the typical examples of OFMT.     

A case of a pleomorphic hyalinizing angiectatic tumor of soft parts with intracytoplasmic hemosiderin pigment apparent upon fine‐needle aspiration cytology

Pleomorphic hyalinizing angiectatic tumors of soft parts are extremely rare low‐grade mesenchymal lesions that frequently occur subcutaneously, especially in the lower extremity. The tumor is histologically characterized by sheets of plump, spindled or rounded cells, and clusters of ectatic blood vessels. It also has a number of previously characterized cytological features such as pleomorphic cells, intranuclear pseudoinclusion, and intracytoplasmic hemosiderin pigments. However, intracytoplasmic hemosiderin has not been carefully evaluated in cytology specimens. Here, we report the case of a 56‐year‐old Japanese man with an encapsulated pleomorphic hyalinizing angiectatic tumor of soft parts that included fine and coarse hemosiderin‐laden tumor cells. The tumor was clinically followed up as a hematoma, but malignant tumors, including malignant melanoma, were suspected because aspiration cytology specimens contained pleomorphic cells with intracytoplasmic brown pigments. The tumor was closely associated with an intratumoral hematoma and a few microscopic satellite lesions. Pleomorphic hyalinizing angiectatic tumor of soft parts should be included in the differential cytological diagnosis of soft tissue tumors if the three cytological features described earlier are present. Enucleation therapy could facilitate local recurrence, as the tumor may have the potential to infiltrate surrounding soft tissue or form satellite lesions. Diagn. Cytopathol. 2015;43:407–411. © 2014 The Authors. Diagnostic Cytopathology Published by Wiley Periodicals, Inc.     

Ossifying fibromyxoid tumor: modified myoepithelial cell tumor? Report of three cases with immunohistochemical and electron microscopic studies

Ossifying fibromyxoid tumors (OFMT) are rare soft tissue tumors of uncertain histogenesis and clinical behavior. Since Enzinger, Weiss, and Liang first described 59 examples in 1989 (Am Surg Pathol. 13:817-827), approximately 150 cases have been reported. Their clinicopathologic features are fairly well characterized and their histogenesis remains unknown. Three examples of soft tissue tumors with typical histopathologic characteristics of OFMT were studied: case 1, a 43-year-old female with a 2.5-cm tumor of the back; case 2, a 56-year-old man with an 8-cm thigh mass; and case 3, an 81-year-old female with a 13.5-cm buttock tumor. For immunohistochemistry, formalin-fixed, paraffin-embedded tissue sections were stained with antibodies against cytokeratin, smooth muscle actin, desmin, vimentin, S-100 protein, EMA, and collagen type IV using standard ABC-peroxidase methods. For electron microscopy, tissue samples fixed in EM-grade buffered formalin were processed according to routine methods. Immunohistochemistry showed that the tumor cells were positive for vimentin and S-100 protein in all 3 cases. Stains for collagen type IV revealed diffusely positive staining in the stroma with a tendency for stronger staining around the cell borders in 2 out of 3 cases. Desmin was positive in one and actin was positive in one other case. By electron microscopy, tumor cells were characterized by centrally located round to oval nuclei with varying amounts of cytoplasm containing scanty cytoplasmic organelles. There were rare profiles of rough-surfaced endoplasmic reticulum (RER) and rare mitochondria with areas of condensed intermediate filaments. No tonofilaments or actin filaments were present. There were multiple short web-like processes, some of which were attached to that of neighboring cells by primitive cell junctions. In all 3 cases, lesional cells showed external lamina (EL), which was abundant in case 1, forming redundant scrolls frequently. In case 2, EL was less prominent and incomplete, and interrupted portions of EL were present only along the periphery of cell columns or nests bordering the stroma. In case 3, which behaved as a malignant tumor, the tumor cells were less differentiated spindle cells with primitive cellular features, and EL was rarely found along the short span of tumor cell borders. In this study, tumor cells in OFMT were polygonal to stellate often with multiple short cytoplasmic processes. The tumor cells were found to form cell clusters attached by primitive intercellular junctions between cytoplasmic processes forming intercellular bridges. The cell borders facing the stroma around cell clusters tended to be flat and had incomplete EL, while no EL was present along the cell borders facing the inner aspect of cell clusters. These ultrastructural findings together with immunophenotypic expression of S-100 protein presented closer resemblance to those of modified myoepithelial cells in pleomorphic adenomas of salivary glands and skin appendages rather than peripheral nerve sheath tumors. The authors conclude that these findings render more support to the hypothesis of myoepithelial histogenesis of OFMT. They also conclude that ultrastructural study not only helps accurate diagnosis, but also may aid in predicting malignant behavior by the degree of deviation from the typical examples of OFMT.     

Calcifying fibrous tumor of the adrenal gland

Calcifying fibrous tumor is an uncommon entity with distinctive pathologic features. Most calcifying fibrous tumors involve the peripheral soft tissues or serosal surfaces, with reports of visceral examples of this lesion being extremely limited. We report the clinical and pathologic features of an unusual case of calcifying fibrous tumor occurring in the adrenal gland of a 32-year-old woman. Microscopically, the lesion was well circumscribed and composed of dense, poorly cellular collagenous tissue, scattered spindle cells, an inflammatory infiltrate consisting of plasma cells and lymphocytes, and dystrophic calcifications. The morphologic diagnosis of calcifying fibrous tumor was supported by diffuse positive immunoreactivity for factor XIIIa and absence of reactivity for muscle specific actin, smooth muscle actin, and anaplastic lymphoma kinase. Although rare, awareness that calcifying fibrous tumor may occur at this particular site is important so as not to confuse this lesion with other mesenchymal neoplasms of the adrenal gland.     

Malignant fibrous histiocytoma of the esophagus

A 78-year-old man presented with an esophageal polyp that was confirmed by Immunohistochemistry and electron microscopy to be malignant fibrous histiocytoma. The tumor was comprised of a proliferation of spindle-shaped cells admixed with bizarre giant cells. These tumor cells were immunoreactive for smooth muscle actin, vimentin, α-1-arrti-chymotrypsin and CD68. Electron microscopic examination revealed the myoflbroblastic and histtocytic features of the tumor cells. No elements of epithelial or myogenic differentiation were found in the tumor. Malignant fibrous histiocytoma of the esophagus is extremely rare, with 10 cases being documented so far in the literature. The differential diagnosis of pteomorphic tumors of the esophagus is discussed.     

Leiomyomatosis peritonealis disseminata with malignant change in a man

Leiomyomatosis peritonealis disseminata (LPD) is a rare clinicopathological entity typically observed in women of reproductive age. We report a case of LPD with malignant change in a man. A 77-year-old man presented with a mass measuring 10 cm in diameter at the terminal ileum and numerous peritoneal small nodules that were revealed by abdominal computed tomography. Right hemicolectomy with lymph node dissection was performed. Macroscopically, a tumor of the terminal ileum consisted of aggregates of small nodular lesions with calcification and necrosis. The wall of the ileum and colon was intact. Microscopically, some of the nodular lesions consisted of neoplastic growths of atypical spindle cells with cellular atypism and abnormal mitoses. A few of these lesions were completely surrounded by smooth muscle bundles. Hemorrhages and necroses were found within the tumor nodules. Immunohistochemically, the tumor cells were positive for vimentin, desmin, muscle actin, α-smooth muscle actin, cytokeratin and p53. The remaining nodular lesions, including small peritoneal lesions, were composed of hypocellular hyalinizing nodules. This case was thought to be LPD with malignant change, although the pathogenesis was uncertain because the tumor cells were negative for estrogen and progesterone receptors.     

A case of soft tissue myoepithelial tumor arising in masticator space

Soft tissue myoepithelial tumors of the head and neck region are very rare, and only one case of soft tissue myoepithelial tumor occurring in the masticator space has been reported in the world literature. A case of soft tissue myoepithelial tumor with benign histomorphology, but with an invasive growth pattern, occurred in the masticator space of a 46-year- old male patient. Magnetic resonance imaging of paranasal sinus/nasopharynx revealed a well-defined, lobulated heterogeneous mass with high signal intensity and dense calcification in the masticator space between the left mandible ramus and pterygoid process. Grossly, the tumor was a well- circumscribed ovoid solid mass and consisted of yellowish gray glistening firm tissue. Histologically, the tumor showed a multinodular growth pattern and consisted of epithelioid cells in chondromyxoid stroma and of spindle-shaped to ovoid cells in the hyaline stroma. The tumor cells appeared bland, and no mitosis or necrosis was found within the tumor. The tumor focally invaded to adhered bone tissue. Immunohistochemically, the tumor cells were diffusely positive for epithelial membrane antigen, smooth muscle actin, but negative for other epithelial markers. Ultrastructurally, the cytoplasm of the tumor cells contained sparse microfilaments and subplasmalemmal densities. Attenuated desmosomes were commonly seen between the tumor cells.     

Epstein-Barr virus-associated post-transplant primary smooth muscle tumor of the liver: Report of an autopsy case

Epstein-Barr (EB) virus-associated primary smooth muscle tumors have been reported in immunosuppressed young patients with acquired immunodeficiency syndrome (AIDS) and young people who have undergone liver transplantation. An autopsy case of EB virus-associated smooth muscle cell tumor in a 21 year old female who received immunosuppres-sive therapy following renal transplantation Is repotted. Multiple tumor nodules were present in the liver, but no primary lesion was found in any other organ. Histologically, the nodules were composed of spindle cells, positive for α-smooth muscle action, which were arranged in fascicles and closely associated with vascular channels, thereby suggesting a vascular smooth muscle cell origin. EB virus infection of the tumor cells was clearly demonstrated by in situ hybridization with an EB virus-encoded RNA 1 (EBER-1) probe. The present case illustrates that EB virus infection may play some role in the development of smooth muscle tumors not only in immunocompromised young patients with liver allo-grafts, but also in those with renal allografts.     

Primary leiomyosarcoma of the pancreas: a case report and review of literature

Primary leiomyosarcoma of the pancreas is a rare tumor for which only 21 reports appear in the world literature. We describe an additional case of pancreatic leiomyosarcoma in a 76-year-old man, who complained of persistent high fever. Histologic examination revealed a pleomorphic spindle cell tumor. Reactivity for muscle-specific actin, alpha-smooth muscle actin, and basement membrane components, along with negative staining for epithelial and neural markers, were consistent with a smooth muscle sarcoma. The patient died of disease 1 year after complete surgical excision. This report highlights the need to use a complete antibody panel in order to accurately immunophenotype pleomorphic malignant tumors of the pancreas. A review of the cases compiled in the literature indicates that pancreatic leiomyosarcoma, like its counterpart arising in deep soft tissues, is an aggressive neoplasm characterized by short survival and a high rate of metastases.