Localized tenosynovial giant cell tumor of tendon sheath. A case report

BACKGROUND: Localized tenosynovial giant cell tumor of tendon sheath (TGCT-L) is a benign, slowly growing lesion with a peak incidence in the third to fifth decade of life. It is thought to arise from the synovium of tendon sheaths, frequently affecting interphalangeal joints of the hands, feet, ankles and knees. Although the histopathologic appearances are well established, only a few reports describe the cytomorphology of this lesion. CASE: A 37-year-old female presented with a slowly growing, nontender mass located near the left ankle joint. The cytologic features of localized tenosynovial giant cell tumor of tendon sheath (TGCT-L) include abundant mononuclear histiocytic cells occurring singly and in three-dimensional tissue fragments, hemosiderin within histiocytes and a few multinucleated giant cells. Subsequently, the histopathologic examination of the surgical specimen was proven to be TGCT-L. CONCLUSION: Fine needle aspiration cytology can be used as a diagnostic tool for early and accurate detection of TGCT-L since the cytologic features combined with clinical details are sufficiently distinctive.     

Cytomorphologic spectrum in paraganglioma

OBJECTIVE: To study the detailed cytologic features of paragangliomas (PGs) and delineate features helpful in predicting behavior. STUDY DESIGN: We performed retrospective analysis of 12 cases cytologically suggested as PG over a period of 10 years. Smears were reviewed for cellularity, pattern, shape, cytoplasm, nuclear features and background. Cytologic diagnosis was correlated with clinicoradiologic features, histologic features and immunocytochemistry. RESULTS: Patient age ranged from 12 to 65 years, with male preponderance; they presented with a mass lesion. Sites involved were head and neck (5), retroperitoneum (5) and mediastinum (2). Smears were cellular; cells were round to oval, plasmacytoid and spindled and seen as scattered, in clusters, acinar and perivascular pattern. The most consistent feature was presence of pink granules. Pleomorphism was present in all but 1 case and less prominent in tumors with metastasis. Mitoses were more frequently seen in malignant cases. CONCLUSION: Cytologic features of PG are diverse. Although there are certain main features, they are not diagnostic unless combined with data on site, histology and ancillary studies. Presence of granules, mild pleomorphism, frequent mitoses and necrosis needs careful evaluation for malignancy potential and warrants close follow-up.     

Cytomorphologic spectrum of carcinoma ex pleomorphic adenoma

OBJECTIVE: To delineate the cytomorphologic features of carcinoma ex pleomorphic adenoma (CPA) and identify the diagnostic pitfalls. STUDY DESIGN: Smears of 14 cases suspected as CPA on fine needle aspiration over a period of 15 years were reviewed. Cytohistologic correlation was done in 10 cases. RESULTS: All cases had a salivary gland mass of 1-16 years' duration, with a rapid increase in size in 10 cases. Epithelial cells predominated over stroma in 11 of 14 cases. Group I showed unequivocal malignant cells admixed with benign epithelial and stromal components of pleomorphic adenoma (PA), which were considered diagnostic of CPA on review. The cytologic differential diagnosis in these cases included mucoepidermoid carcinoma, carcinosarcoma and metastatic adenocarcinoma. Group II comprised 7 cases suspected to be cellular PA with atypia or CPA. These showed mild to moderate degrees of pleomorphism, absence of unequivocal malignant cells, and a variable proportion of benign epithelial and stromal components. Four of them were histologically confirmed as CPA. CONCLUSION: Sampling error is an important cause of diagnostic pitfalls. Correlation with clinical data is essential in diagnosis of CPA on cytology. In a proper clinical setting, extensive fine needle aspiration sampling should be done initially. Any degree of nuclear atypia in PA should be documented, alerting the clinician and histopathologist to the possibility of CPA.     

Serglycin induces osteoclastogenesis and promotes tumor growth in giant cell tumor of bone

Giant cell tumor of bone (GCTB) is an aggressive osteolytic bone tumor characterized by the within-tumor presence of osteoclast-like multinucleated giant cells (MGCs), which are induced by the neoplastic stromal cells and lead to extensive bone destruction. However, the underlying mechanism of the pathological process of osteoclastogenesis in GCTB is poorly understood. Here we show that the proteoglycan Serglycin (SRGN) secreted by neoplastic stromal cells plays a crucial role in the formation of MGCs and tumorigenesis in GCTB. Upregulated SRGN expression and secretion are observed in GCTB tumor cells and patients. Stromal-derived SRGN promotes osteoclast differentiation from monocytes. SRGN knockdown in stromal cells inhibits tumor growth and bone destruction in a patient-derived orthotopic xenograft model of mice. Mechanistically SRGN interacts with CD44 on the cell surface of monocytes and thus activates focal adhesion kinase (FAK), leading to osteoclast differentiation. Importantly, blocking CD44 with a neutralizing antibody reduces the number of MGCs and suppresses tumorigenesis in vivo. Overall, our data reveal a mechanism of MGC induction in GCTB and support CD44-targeting approaches for GCTB treatment.Subject terms: Bone cancer, Cancer microenvironment, Mechanisms of disease     

Ultrastructure of an anaplastic giant cell tumor of the thyroid

A case of anaplastic, multinucleated giant cell tumor of the thyroid was studied by light and electron microscopy. The coexistence of anaplastic sarcomatous tumor and well differentiated follicular carcinoma, and the presence of desmosomes among the mononuclear cells suggested that this tumor originates in thyroid follicular cells. The multinucleated giant cells, which characterize this thyroid tumor, appeared to be formed by fusion of follicular carcinoma cells and mononuclear epithelial cells, and not by nuclear division without cytoplasmic division.     

Clinical anatomy of the m. flexor carpi radialis tendon sheath

At the transitional zone from the forearm to the hand the insertion tendon of the m.flexor carpi radialis (FCR) glides on a fibrous and fatty cushion, which is connected dorsally with the joint capsule of the radiocarpal articulation. The tendon distally crosses the palmar side of the scaphoid tubercle and enters the dorsally curved rim of the trapezoid tubercle. At the level of the wrist joint the narrow tendon sheath begins, which extends to the insertion at the metacarpus. Immediately after entering the gliding tunnel the tendon branches off radially as a rule with an accessory fibre strand 8 mm in width to the scaphoid, trapezium and the joint capsule between these two bones. The insertion tendon regularly is attached to the palmar and radial surfaces of the second and third metacarpal bones. The wall of the osteofibrous gliding tunnel can be prominent following trauma, inflammation or arthrosis deformans in the trapezio-scaphoideal joint and may irritate the tendon (tendovaginosis stenosans). Against resistance forces pain will occur in the wrist joint during palmar flexion. The typical point of tenderness is situated at the entering of the tendon in the thenar region. Operative decompression will be effective by opening the radial wall of the tendon sheath from the carpal tunnel.     

Langerhans cell histiocytosis in lymph nodes. Cytomorphologic diagnosis and pitfalls

OBJECTIVE: To delineate the cytomorphology of Langerhans cell histiocytosis (LCH) in lymph nodes. STUDY DESIGN: Nine histologically documented LCH cases with a prior lymph node aspirate and five more cases in which a cytologic diagnosis of LCH was rendered in a background of corroborative clinical and radiologic findings were included in a retrospective study over a 12-year period (January 1988-January 2000). Papanicolaou- and May-Grünwald-Geimsa-stained smears were reviewed by two independent observers. Staining for S-100 protein was available in four cases. RESULTS: Nine cases had multisystem involvement, while in five cases only lymph nodes were involved. The ages ranged from 5 months to 27 years, with 11 males and 3 females. An initial cytologic diagnosis of LCH had been rendered in six, suspected in four and missed in four. On review, all were reclassified as LCH except two cases, which were still thought to be reactive and necrotizing lymphadenitis. The pathognomic feature of LCH, the "LCH cell," was identified in 12 of 14 cases along with varying numbers of eosinophils, polymorphs and lymphocytes. Giant cells were seen in six cases, and plasma cells were rarely seen. CONCLUSION: Lymph node involvement by LCH can be identified by fine needle aspiration in 85% of cases. The presence of the LCH cell is a must. The differentials to be considered are dermatopathic lymphadenitis, sinus histiocytosis with massive lymph-adenopathy, Hodgkin's lymphoma and malignant histiocytosis.     

Cytologic features of malignant peripheral nerve sheath tumor

OBJECTIVE: To study the cytomorphologic features of malignant peripheral nerve sheath tumor (MPNST), including the epithelioid cell variant, and to establish differential diagnostic features with benign neurogenic tumors and other sarcomas. STUDY DESIGN: Cytologic smears from primary, recurrent and metastatic tumors in 10 patients with MPNST were reviewed. Three patients had neurofibromatosis 1 (NF1), and in two others the tumor arose from a preexisting neurofibroma. Immunocytochemical evaluation of S-100 protein was performed in four cases. A complete pathologic study was available in all cases. To assess the validity of morphologic recognition, a blinded study, including eight cases of spindle MPNST among smears from histologically proven schwannomas, synovial sarcomas, leiomyosarcomas, malignant fibrous histiocytomas and liposarcomas, was performed. RESULTS: Neurogenic differentiation was recognizable in four cases (differentiated), while the other four (anaplastic) were indistinguishable from other pleomorphic sarcomas. The presence of elongated, slender, often wavy nuclei and less commonly a delicate, fibrillary metachromatic stroma were features suggestive of nerve sheath differentiation. Other cytologic, as well as clinical, features permitted their identification as malignant. Two cases of epithelioid MPNST disclosed large, polygonal to plasmocytoid tumor cells without specific cytologic features. S-100 immunoexpression was positive in two of the four cytologic samples tested. CONCLUSION: Although no morphologic findings are specific to MPNST, the above-mentioned cytologic features may suggest, in differentiated cases, its neurogenic differentiation. On the basis of morphologic features alone, the diagnosis of anaplastic and epithelioid MPNST is not possible, and immunocytochemical and ultrastructural studies are necessary. A specific cytodiagnosis is possible in recurrences, metastases and cases of NF1 or a preexisting neurofibroma.     

Expression and localization of extracellular matrix metalloproteinase inducer in giant cell tumor of bone

Matrix metalloproteinases (MMPs) are regarded as a significant regulator in tumor invasion and metastasis. Previous studies have shown that extracellular matrix metalloproteinase inducer (EMMPRIN) in tumor cells induces the synthesis of MMPs. EMMPRIN is abundantly present on the surface of tumor cells and stimulate adjacent stromal cells to synthesize MMPs to induce tumor progression. Giant cell tumor (GCT) of bone is a benign but locally aggressive primary neoplasm of bone. The spindle-shaped mononuclear stromal cells are considered to be the tumor components of GCT, which are capable of inducing osteoclast formation by recruiting the circulating monocyte and macrophage. In this study, we proposed that EMMPRIN is associated with the biological progression and aggressiveness of GCT. We have conducted semi-quantitative RT-PCR to determine the correlation of EMMPRIN expression with the clinical stage of GCT. We have also examined the cellular localization of EMMPRIN in GCT using in-situ hybridization (ISH) and Immunohistochemistry (IH). The results showed that EMMPRIN was present in GCT and its mRNA levels were associated with the clinical stage of GCT. Higher expression level of EMMPRIN was observed in GCT with advanced stage (stage III). There was a great significance (P < 0.05) of EMMPRIN expression between stage I & II and stage III GCTs. Both ISH and IH demonstrated that EMMPRIN is present at the multinuclear osteoclast-like giant cells of GCT, with strong immunostaining on the cell membrane. The stromal-like tumor cells were also positively stained but the intensity was weaker. Interestingly, the production of EMMPRIN in osteoclast-like cells of GCT seems to be regulated by stromal-like tumor cells. Receptor activator of NF-kappaB ligand (RANKL), which has been previously shown to be produced by the stromal-like tumor cells for the recruitment of osteoclast-like giant cells in GCT, enhanced the expression of EMMPRIN mRNA during the differentiation of macrophage-like RAW(264.7) cells into osteoclasts. In short, our studies suggest that EMMPRIN may be an important regulatory factor involved in the biological behaviors of GCT.     

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.