Multinucleated Tumor Giant Cells Research Articles

Pleomorphic Liposarcoma Cytologically Detected in Hemosiderotic Pleural Effusion: Pitfalls Mitigated by Cytologic Clues and Cellblock Immunocytochemistry.

Sarcomatous serous effusions are uncommon and diagnostically challenging. Dedifferentiated and pleomorphic liposarcomas are rare tumors in pleural effusions revealing highly pleomorphic tumor cells mimicking carcinoma, mesothelioma, melanoma, and other sarcomas. Hematothoracic effusions further complicate the cytologic diagnosis. Correct cytologic recognition is important. We report pleomorphic liposarcoma cytologically detected in effusion fluid in a 56-year-old man who presented with a massive unilateral pleural effusion. ThinPrep showed hemorrhagic effusion fluid characterized by lysed red blood cells, foamy macrophages, and siderophages intermixed with highly pleomorphic predominantly naked mononuclear and giant nuclei. The aggregated siderophages and vacuolated macrophages could be mistaken for tumor cells, whereas the bare nuclei may be missed as nonspecific degenerate changes. Cellblock sections showed highly pleomorphic mononuclear and multinucleated giant tumor cells with diagnostic lipoblasts, intermixed with foamy macrophages and siderophages. Cellblock immunocytochemistry showed staining for vimentin and S-100 protein in the tumor cells. Other lineage-specific immunomarkers were negative. CD68 and calretinin revealed frequent background macrophages and scarce mesothelial cells. The tumor cells were negative for MDM2 and CDK4. The entertained cytopathologic diagnosis was pleomorphic liposarcoma. Core needle biopsy was procured from the mass. The histopathologic features and immunoprofile of the tissue specimen matched the cytopathologic and immunocytochemical findings confirming the cytologic diagnosis of pleomorphic liposarcoma. Pleomorphic liposarcoma is an unexpected cytologically challenging finding in effusions, particularly when compounded by pitfalls introduced by hemosiderotic fluid. Attention to certain cytologic clues mitigate pitfalls. Cellblock is a valuable diagnostic tool when integrated with relevant negative and positive immunocytochemical markers.

Icariside I reduces breast cancer proliferation, apoptosis, invasion, and metastasis probably through inhibiting IL-6/STAT3 signaling pathway.

Breast cancer is a common malignancy in women. More than 90% of breast cancer deaths are caused by metastasis. Epimedii Folium (EF) is a commonly used herb with anti-tumor benefits, but its underlying mechanisms and active components for breast cancer prevention are little understood. This study assessed the therapeutic role of Icariside I (ICS I) in Epimedium flavonoids (EF) on lung metastasis of breast cancer, including the underlying mechanism. Western blot, RT-qPCR, wound healing assay, colony formation assay, and flow cytometry were used to investigate the inhibition of breast cancer cells growth and migration by EF and ICS I through disrupting the IL-6/STAT3 pathway. Combined with 4T1 breast cancer model in mice, Western blot, RT-qPCR, Hematoxylin and Eosin staining, immunohistochemistry were used to evaluate the therapeutic role of ICS I in proliferation, apoptosis, invasion, and metastasis of breast cancer. EF can inhibit STAT3 phosphorylation and reduce the colony formation and migration of breast cancer cells. Detecting the active ingredients in EF, we found ICS I can reduce the activation of STAT3 in 4T1 breast cancer cells, impair colony formation and migration. Moreover, ICS I induced cells G1 phase arrest and modulated Cyclin D1, CDK4, bcl-2, and bax to inhibit proliferation and survival of breast cancer cells. Similarly, the in vivo studies demonstrated that ICS I significantly suppressed tumor development and lung metastasis in the 4T1 mouse model. Tumor cells in vehicle group were arranged in a spoke-like pattern with obvious heterogeneity, and multinucleated tumor giant cells were seen. But, the tumor cells in the ICS I group were disorganized and necrotic lysis was seen in some areas. In ICS I-treated group, tumors' STAT3 phosphorylation level, IL-6, Cyclin D1, CDK4, bcl-2, and vimentin expression were downregulated, bax and cleaved caspase 3 expression were upregulated. In the lung tissue, we could find less metastasis of breast cancer cells and less lung injury in the ICS I group. Besides, the expression of metastasis-related genes MMP9 and vimentin was decreased in the lung tissue of ICS I group. These findings suggest that ICS I can inhibit breast cancer proliferation, apoptosis, invasion and metastasis probably via targeting IL-6/STAT3 pathway. Therefore, ICS I has the potential to become an innovative therapeutic candidate to breast cancer prevention and treatment.

Clear Cell Renal Cell Carcinoma With Syncytial-Type Multinucleated Giant Tumor Cells: A Clinicopathologic Study of 14 Cases.

The presence of syncytial-type multinucleated giant tumor cells with emperipolesis in clear cell renal cell carcinoma (RCC) is uncommon, with only 31 cumulative published cases to date. After a rereview of 125 clear cell RCC of World Health Organization/International Society of Urological Pathology grade 3 or 4, 14 clear cell RCCs with admixed syncytial-type giant cells (to our knowledge, the largest series to date) were found with a mean patient age of 67 years and with no sex difference (M = 7, F = 7). Mean tumor size was 7.3 cm. The syncytial-type giant cells comprised between 2% and 20% of the tumor and were present mainly around areas of necrosis. Five tumors were staged as pT1 or pT2, 8 as pT3, and 1 as pT4. Other findings included sarcomatoid differentiation (3/14), rhabdoid differentiation (4/14), and emperipolesis (12/14). Positive immunostains included keratin AE1/AE3 (13/13), carbonic anhydrase 9 and CD10 (12/14 each), vimentin (8/14), EMA (5/12), and alpha-methyacyl-CoA racemase (3/12). Keratin 7, keratin 20, human melanoma black 45, KIT, TFE3, cathepsin K, CD68, CD61, and beta human chorionic gonadotropin were negative. Six of 13 patients had recurrence or metastases during a mean follow-up time of 56 months. Four of 13 patients died of disease, 2 of 13 patients were alive with the disease, and 7 of 13 patients had no evidence of disease. Although the incidence of finding syncytial-type multinucleated giant tumor cells in clear cell RCC is low (approximately 1.2%), given that a subset of the patients showed poor outcomes while lacking other poor histologic parameters (eg, sarcomatoid or rhabdoid differentiation), it may be prudent to recognize and report this feature when encountered.

High-grade B-cell lymphoma with MYC and BCL2 rearrangements with abundant multinucleated giant tumor cells.

High-grade B-cell lymphoma with MYC and BCL2 rearrangements with abundant multinucleated giant tumor cells.

P029: Are Reed-Sternberg cells stuck in mitosis by short nucleoplasmic bridges as a consequence of centromeric instability?

Background: Multinucleated giant tumor cells are frequently observed in lymph nodes of untreated lymphoma patients. Malignant Hodgkin lymphoma (HL) cells i. e. small Hodgkin and large bi- or multinucleated Reed-Sternberg (HRS) cells are characterized by genomic instability and downregulation of numerous key regulators of e.g. cell cycle, spindle apparatus, cytokinesis and cell lineage differentiation. So far, the formation of HRS cells remains obscure. We have demonstrated previously that telomere instability is involved in the proliferation of small cells into large binucleated cells. Here, we have used a collection of HL cell lines to analyze the successive steps involved in the transformation of the mononucleated into the multinucleated RS-like cells. Materials and Methods: Seven HL cell lines and 30 HL lymph nodes were used. Cytokinesis-block micronucleus assay and telomere and centromere staining followed by the M-FISH technique were employed to analyze chromosomal instability. DNA repair pathways were investigated. Results: We demonstrate that telomere dysfunction in HL cell lines is associated with the formation of dicentric chromosomes with both centromeres in close proximity, but also with a high rate of formation of micronuclei. Two morphologically different types of nucleoplasmic bridges (NPBs) were observed: (1) Long NPBs related to telomere dysfunction and chromosome fusions, and (2) short NPBs related to centromere breakpoints with configurations of cells looking like “stuck” together as binucleated cells. Short NPBs and binucleated cells were seen in the cultures of all HL cell lines. However, each HL cell line was characterized by an individual signature of the proportion of long and short NPBs, which correlated with centrosome amplification and formation of stable binucleated cells. Similar mechanisms were identified in HL patient lymph nodes prior to treatment, thus underscoring the biological significance of our findings in cell cultures. Transcriptome analysis confirmed the variations in the DNA repair pathways regarding the rate of large cells among the different HL cell lines. Conclusion: The formation of dicentric chromosomes related to centromere instability, and short NPBs were associated with the emergence of binucleated cells through different mechanisms. Our findings open a novel route to understanding the transition from mononucleated cells to multinucleated cells in HL and in other B-cell lymphomas.

A Case of Undifferentiated Pleomorphic Sarcoma of the Right Lower Extremity

Objective: To strengthen the understanding of the disease and treatment of undifferentiated pleomorphic sarcoma (UPS). Methods: The clinical data of an elderly male patient with UPS admitted to Hebei Provincial People’s Hospital in September 2020 were retrospectively analyzed, and relevant literatures were reviewed. Results: The patient was an elderly male, 74 years old. The color Doppler ultrasonography of the body surface mass showed a solid mass of subcutaneous soft tissue on the lateral side of the right thigh. Undirected arrangement, multinucleated tumor giant cells with strange shapes are seen, and mitotic figures are more common. Immunohistochemical staining: CKpan (-), Vimentin (+), Desmin (-), SMA (partial+), EMA (-), S100 (-), CD34 (vascular+), MyoD1 (-), Myogenin (-), Myoglobin (-), CD68 (-), Caldesmon (-), Ki-67 (about 40% active area). After six months of follow-up, no tumor recurrence was found. Conclusion: UPS is a rare malignant tumor in clinic. It has no specific clinical manifestations, imaging manifestations, histopathology and immunohistochemical staining. It is an exclusive diagnosis. Complete tumor resection is required, and pathological examination is the gold standard for diagnosis. Its long-term prognosis is relatively poor.

Potential Anti-carcinogenic Effect of Acetazolamide, a Carbonic Anhydrase Enzyme Inhibitor, in Diethylnitrosamine - Induced Hepatocarcinogenesis in Rats

Abstract Background Despite the progress achieved in early detection and treatment of HCC, it still accounts for a significant number of cancer-related deaths worldwide. Tumoral microenvironment acidity plays a pivotal role in tumoral cell survival, tumoral progression and metastasis. CA-IX and XII are two of several mechanisms by which tumor maintain optimal intracellular pH at the expense of the extracellular environment that turns into acidic pH. ACT is a CA inhibitor that is used in many medical indications. It is effective, safe and inexpensive. It has some side effects and it may be even contraindicated in some cases. Aim of the work To evaluate the possible anticarcinogenic role of ACT in DEN-induced HCC animal model. Materials and Methods This study showed that using DEN for 10 weeks caused significant increase in the levels of AST, ALT, total bilirubin, direct bilirubin and AFP and significant decrease in albumin level in DEN-induced HCC rat groups when compared to normal control rats. Administration of ACT for 3 weeks in ACT-treated DEN-induced HCC group caused marked improvement in the mentioned biochemical measurements (AST, ALT, total bilirubin, direct bilirubin and AFP) when compared to DEN-induced HCC rat group without ACT treatment, yet still higher than the lab values of normal control group. Results The present study demonstrated that using DEN in rat groups had induced polyhedral to round hepatocytes with dense, centrally located vesicular nuclei. The neoplastic areas showed poorly differentiated large cells with hyperchromatic nuclei and prominent nucleoli. The neoplastic cells showed anisokaryosis, anisocytosis, and deeply basophilic scanty cytoplasm and frequent mitotic figures mostly Grade III. The hepatic lobule displayed disorganization of hepatic cords with hyperplasia of Kupffer cells, multinucleated tumor giant cells with prominent basophilic nuclei and basophilic spindle cells. Conclusion Acetazolamide showed significant antitumor effect in DEN-induced HCC in rats, making it a promising agent to use against HCC either individually or in combination with any other therapeutic modalities. Further researches should be conducted in this anti HCC aspect.

Epithelioid glioblastoma with BRAF V600E mutation: a clinicopathological and molecular study

Objective: To investigate the clinicopathological and molecular characteristics of the epithelioid glioblastoma (eGBM) with BRAF V600E mutation. Methods: Sixteen cases of eGBM with BRAF V600E mutation diagnosed at the West China Hospital of Sichuan University, China from 2012 to 2019 were collected. Their clinicopathological and molecular characteristics were analyzed. Results: The range of patients' age was from 7 to 61 years (median 31.5 years). There were 4 males and 12 females, with a male to female ratio of 1∶3. Eleven cases were newly diagnosed eGBM and five cases had a previous history of astrocytomas. Most of the tumors were located in the cerebral hemisphere, often in the frontal lobe, with an average diameter of 4.6 cm (2.0-8.0 cm). The tumors were composed of relatively uniform, closely packed epithelioid cells, some showing discohesion, with distinct cell membrane, eosinophilic cytoplasm, eccentric nuclei, distinct nucleoli and mitotic activity. Palisaded/coagulative necrosis was seen in all cases. Glomerular microvascular proliferation was seen in most of the cases, while mono-or multi-nucleated tumor giant cells were seen in some cases. Focal sarcomatoid area was seen in 2 cases, and focal pleomorphic xanthoastrocytoma (PXA)-like area was seen in 3 cases. Immunohistochemistry showed variable positivity for GFAP, Olig2 and p53. The median Ki-67 index was 30% (10%-50%). Only one case lost ATRX protein expression. Sanger sequencing identified the BRAF V600E mutation in all sixteen patients. Five cases also had mutations in the TERT gene promoter. No IDH1 (R132) or IDH2 (R172) mutation was detected. Surgical resection of the tumors was performed for all patients, and 3 patients also received adjuvant radiotherapy and chemotherapy. Follow-up data were available for 15 patients, with a follow-up time of 1-89 months (median 10 months). Among the 15 patients, 7 patients died of disease and another 5 patients had recurrences. The overall survival time of the patients under 35 years of age was significantly longer than that of the patients aged 35 years or older (P=0.014), but their progression-free survival was not statistically different (P=0.232). Conclusions: eGBM with BRAF V600E mutation is more commonly detected in young women than other the populations (i.e. elderly or male). The epithelioid morphology should include rhabdoid meningioma, anaplastic PXA, atypical teratoid/rhabdoid tumor, metastatic tumors, and melanoma in its differential diagnosis. PXA-like area is observed in some eGBM cases, suggesting a relationship of these two types of tumor. eGBM is a high-grade malignant tumor and most of the cases show recurrences or deaths in a short-period time. The younger patients have a relatively better prognosis than the older ones.

Expression of Platelet Derived Growth Factor a, Its Receptor, and Integrin Subunit Alpha V in Feline Injection-Site Sarcomas

Abstract Injection-site sarcomas are considered an important entity in veterinary oncology, especially in cats. The current study investigated the immunohistochemical expression of platelet-derived growth factor A (PDGFA), platelet-derived growth factor receptor-α (PDGFR-α), and integrin alpha subunit v in feline injection-site sarcomas (FISS). A total of 14 paraffin-embedded tissue samples previously diagnosed as soft tissue sarcomas were selected from the departmental archive and sectioned at 5µm using a microtome. Tissue sections were stained with Hematoxylin & Eosin, Alcian blue-Periodic Acid Schiff (AB-PAS), Masson’s Trichrome, and immunohistochemically for PDGFA, PDGR-α, and integrin alpha v. The majority of the tumors were fibrosarcomas (n=13/14), except one case of myxoid liposarcoma. The tumors occurred at sites commonly used for injections or vaccine administration. Histologically, tumors were characterized by peripheral infiltration of mononuclear cells mainly lymphocytes, variable sized central necrotic areas, and many multinucleated tumor giant cells. AB-PAS staining revealed the presence of myxoid or mucinous areas in (8/14) tumors while trichrome staining demonstrated a variable amount of collagenous stroma in 12/14 tumors. Vimentin immunoreactivity was observed in all the tumors while smooth muscle actin and muscle actin staining was noticed in four and two cases, respectively. PDGFA and PDGFR-α immunoexpression was observed in all 14 cases while integrin alpha v in 13/14 cases. The results of the current study indicate that fibrosarcoma is the major morphologic phenotype of FISS. The PDGFA, its receptor, and integrin alpha v immunoexpression are increased in these tumors in cats which elucidates their role in the pathogenesis of FISS.

Clear Cell Sarcoma of the Premaxillary Soft Tissue: A Case Report

Abstract Casestudy: Clear cell sarcoma of soft tissue (CCSST) is a rare translocation-associated sarcoma which uncommonly presents in the head and neck region. Because the tumor expresses markers of melanocytic differentiation, it can be difficult to distinguish from malignant melanoma and epithelioid malignant peripheral nerve sheath tumor (MPNST), necessitating clinical correlation and ancillary testing specifically fluorescence in situ hybridization (FISH) for EWSR1 rearrangement. Here we report a case of CCSST involving the premaxillary soft tissue. A 61-year-old male without significant past medical history presented with a right premaxillary subcutaneous mass which was slowly enlarging over the course of three years. During surgical resection of the mass, the infraorbital nerve was noted to course into the tumor. Histologic sections revealed a 2.5 cm mass composed of a nodular proliferation of epithelioid tumor cells with pale eosinophilic to vacuolated cytoplasm, large vesicular nuclei with prominent nucleoli, areas of punctate necrosis, and a mitotic rate of 10 mitoses per 10 high power fields. Scattered multinucleated tumor giant cells were also present. No pigment was identified. By immunohistochemistry, the tumor cells were diffusely positive for SOX-10 and S-100 and negative for HMB45, MART1, MITF, inhibin, calretinin, p63 and smooth muscle actin. FISH was positive for EWSR1 rearrangement. Altogether, the morphologic, immunohistochemical and cytogenetic findings supported the diagnosis of CCSST. Because the surgical margins were negative for malignancy, the patient did not require additional surgery but will be receiving adjuvant radiation therapy. Although rare in the head and neck, CCSST should be considered in the differential diagnosis when dealing with an epithelioid soft tissue tumor that expresses any melanocytic markers, and a definitive distinction from malignant melanoma and epithelioid MPNST can be achieved by utilizing FISH for EWSR1 rearrangement.

Giant multinucleated plasma cells in relapsed plasma cell myeloma.

A 47-year-old woman was diagnosed with plasma cell myeloma in 2018, received first-line induction chemotherapy, and made a partial response. She then received two cycles of DT-PACE chemotherapy. Her paraprotein levels remained static and a repeat bone marrow test in February 2019 revealed persistent bone marrow involvement by plasma cell myeloma showing usual (mononuclear) morphology with no multinucleated giant cells. She was treated with daratumumab as a bridge to an autologous stem cell transplant in June 2019. Her day 100 post autograft bone marrow trephine biopsy contained a plasma cell population making up 10% of all nucleated cells. More than 95% of the atypical plasma cells showed multinucleated giant cell morphology containing up to 40 nuclei. On immunohistochemistry, these multinucleated giant cells showed positive staining for CD138, CD38, and CD56 and were lambda restricted. CD45 was negative. Bone marrow trephine sections stained (clockwise from top left) with H&E, and for CD138, lambda light chains, and CD38. Multinucleated tumor giant cells are thought to form by two mechanisms: by cell-cell fusion via syncytins or as a result of a failure of cytokinesis at the end of the anaphase stage of mitosis. Occasional case reports of giant multinucleated plasma cells have been published since the 1970s. However, the presence of giant plasma cells with more than 10 nuclei is extremely rare. One previous case had also been treated with daratumumab, an IgG1k monoclonal antibody directed against cell surface CD38 (Guijarro F, Rozman M, Matutes E. Multinucleated giant myeloma cells after failure of daratumumab therapy. Br J Haematol 2018;181:432). Plasma cell membrane alterations promoting cell-cell fusion may be a side effect of immunotherapies targeting cell surface molecules. Giant multinucleated plasma cells may be observed more frequently as such immunotherapies become increasingly used.

Rectal Perivascular Epithelioid Cell Tumor With Partial CD117 Expression and Giant Cells

Abstract Perivascular epithelioid cell tumor (PEComa) is a rare entity, characterized as a mesenchymal tumor with coexpression of melanocytic and smooth muscle markers. The involvement of the gastrointestinal tract is described in up to 100 cases in the English literature. Rectal PEComas are even more uncommon, with only 10 previously described cases. We present the case of a 62-year-old man with rectal PEComa with some unusual features, such as gastrointestinal stromal tumor–like CD117 positivity and HMB45 (human melanoma black-45)–positive multinucleated giant tumor cells. After 12 months' follow-up, the patient is alive with no radiologic, endoscopic, or histologic evidence of disease recurrence.

Patterns of Regression in Breast Cancer after Primary Systemic Treatment.

Despite national guidelines, the evaluation of effects of primary systemic treatment (PST) in breast cancer is a complex challenge. Our aims were to evaluate the response patterns focusing on correlations of radiological and pathological tumor size, regression heterogeneity in different molecular subtypes, cellularity changes and the incidence of enlarged, multinucleated neoplastic cells related to therapy. Slides of pretreatment biopsies and resection specimens of consecutive cases were reevaluated focusing on heterogeneity of regression per whole slide, and 40x or 100x magnification fields. Alteration in cellularity and the presence of multinucleated tumor giant cells were noted. The correlation of pathological and radiological sizes and their alterations were analyzed by Spearman rank correlation. The present study included 106 tumors. A decrease in size (84.9%) and cellularity (76.4%) was noted in all molecular subtypes. Inhomogeneous regression was found in 45.3%, with minor inhomogeneity in the majority. Scatter pattern regression was seen only in 8 cases (7.5%). Significant correlations were found between the pathological and radiological sizes (p = 0.02), and between the alterations of cellularity and pathological and radiological size (p = 0.04; p = 0.03, respectively). Multinucleated tumor giant cells were noted in 17.9% (n = 19), nearly exclusively in cases treated with PST including taxanes. Regression inhomogeneity following PST is present in about half of the cases, and is not related to molecular subtypes. The evaluation of the maximum area of the tumor bed is recommended for the proper evaluation of regression. Multinucleated tumor giant cells are related to PST including taxane derivate, and may cause upgrading.

Colonic Leiomyosarcoma: A Rare Entity

64 year-old male who presented for age appropriate screening colonoscopy with negative review of systems and physical examination. Colonoscopy showed a mass in the sigmoid colon at 28cm from anal verge. The mass measured 3-4cm in size, presenting as indurated with superficial ulcerations. Laboratory tests, including CEA and CA 19-9, were unremarkable. CT imaging showed a thickened area of proximal sigmoid colon suspicious for underlying neoplasm. Patient underwent left hemicolectomy with pericolic lymph node resection. On gross examination, a solid polypoid, intraluminal, and submucosal mass measuring 3.6cm X 2.7cm X 1.6cm was found. Microscopically, tumor was composed of elongated spindle cells with high cellularity, cytologic pleomorphism, and nuclear atypia including multi-nucleated tumor giant cells. There was brisk mitotic activity with occasional atypical mitotic figures (mitotic counts of >10 mitoses per 10 hpf). No tumor necrosis was seen. The tumor cells focally infiltrated the mucosa with surface ulceration and also extended focally into the superficial muscularis propria. The proximal, distal and deep margins of resection were negative for the tumor. The tumor cells were immunoreactive for smooth muscle markers (desmin and SMA), and negative for GIST markers (CD117 and DOG1) and neural marker (S100). Trichome stain was used to highlight the tumoral smooth muscle fibers. Pericolic lymph nodes were negative for tumor cells. Leiomyosarcomas are extremely rare and aggressive type of mesenchymal tumors. Leiomyosarcomas stain negative for KIT, CD34, and DOG1 and positive for SMA and desmin. Leiomyosarcomas occur most commonly in small intestine (45%) and colon (38%). Leiomyomas constitute the most common colonic mesenchymal tumors. Colonic leiomyosarcomas have been reported in only 12 adult cases in the US. The only known poor prognostic factor reported is tumor size >5cm. They can range from 3-25cm. Management includes imaging to assess for metastatic disease. Surgery is a treatment of choice for localized soft tissue sarcomas. There is a high recurrence rate even after surgery. Leiomyosarcomas have poor sensitivity to anthracycline based chemotherapy consisting of doxorubicin and dacarbazine. In conclusion, we presented a case of leiomyosarcoma of left colon. The tumor was an intraluminal polypoid mass that was removed in its entirety with negative margins. No evidence of metastatic disease was found. The patient is now being followed closely.

Establishment and characterization of a cell line from human adenoid cystic carcinoma of the lacrimal glands and a nude mouse transplantable model.

Using tissue block culture techniques, we established a new human tumor cell line derived from adenoid cystic carcinoma of the lacrimal glands (LACC-1). The LACC-1 cell line was successfully subcultured for more than 100 passages during the last two years. The outgrowth of cells was observed by day 5 after seeding, and then the cells were generated slowly. The first passage proceeded by day 32, and the classical epithelioid cell colonies formed by day 69 after inoculation. After eight passages, homogeneous epithelioid tumor cells appeared when we combined continuous passage, mechanical scraping, repeated adherence, and dissociation methods to remove the fibroblast cells. LACC-1 cells appeared as a histologically solid pattern and continuous passage culture. The population doubling time was approximately 37.1 h. LACC-1 cells appeared as an epithelioid monolayer culture on the cell culture flask and presented with a cobblestone-like appearance when they reached confluency. The nucleus was large and round with many abnormal mitoses. The nucleoplasm ratio was high. Multinucleated tumor giant cells appeared. LACC-1 cells showed a tendency to have overlapping growth without contact inhibition when the cell density continued to increase. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that the LACC-1 cells were malignant tumor cells that were poorly differentiated. The surface of the LACC-1 cells exhibited affluent microvilli, protuberances and filopodia under SEM. The no. 84 generation LACC-1 cell line was inoculated subcutaneously into the subaxillary of nude mice and the tumorigenic potential was evident. The formation rate of the transplanted tumors was 100% at day 7 after inoculation. This finding showed that the LACC-1 cell line was malignant with tumorigenic ability. The xenograft tumors retained the same histological characteristics of a solid pattern as the LACC-1 original tumor after inoculation for 49 days. Under TEM observation, the xenograft tumor cells had the same ultrastructure as the LACC-1 cells. Immunohistochemical examination revealed the similarity of both cytoskeletal proteins (e.g., cytokeratin, vimentin, desmin and α-SMA) and S-100 expression in the original tumor, LACC-1 cells and xenograft tumors. Immunoreactivity of these proteins was gradually decreased in these three tissues. Reverse transcription-polymerase chain reaction demonstrated that the xenograft tumors originated from the human. Based on these results, the LACC-1 cell line provides a useful model for studying the biological characteristics of human ACC of the lacrimal glands.

On the origin of giant cells in Hodgkin lymphoma

Multinucleated giant tumor cells are frequently observed in tissue sections of lymphoma patients. In Hodgkin lymphoma (HL), these cells are pathognomonic for the disease and named Reed-Sternberg (RS) cells. Despite the well-described disease-promoting functions of RS cells, their development has remained obscure. We addressed this open question by continuous live cell imaging to observe the generation of RS cells. Single-cell tracking of HL cell lines revealed that RS cells develop from mononucleated progenitors that divide and subsequently re-fuse, before they grow and become multinucleated giant cells. Thus, RS cell generation is neither due to cell fusion of unrelated Hodgkin cells nor to endomitosis, as previously suggested. In the majority of cases, re-fusion of daughter cells was preceded by an incomplete cytokinesis, visualized by a persistent microtubule bridge connecting the cells. This surprising finding describes a novel mechanism for the formation of multinuclear giant cells with potential relevance beyond HL.

Pleomorphic giant cell carcinoma of the urinary bladder

Pleomorphic giant cell carcinoma is a rare aggressive variant of urothelial carcinoma characterized by the presence of highly pleomorphic bizarre tumor giant cells similar to giant cell carcinoma of the lung. Although mentioned in the 2004 WHO classification as a type of urothelial carcinoma with giant cells, characteristics of pleomorphic giant cell carcinoma were described in the literature only in 2009 when Lopez Beltran et al . reported a series of 8 cases. It occurs more commonly in older males (ages ranging 55–88 years) with patients presenting with hematuria, dysuria or frequency. The pleomorphic giant cell component in the reported series varied from 20% to 100% of the tumor. This tumour has expansile masses of pleomorphic epithelioid tumor with bizarre anaplastic multinucleated and mononu-cleated tumor giant cells. Extensive necrosis is common. Tumor cells have abundant cytoplasm, and have frequent typical or atypical mitotic figures. Tumour cells are positive for CK7, CAM 5.2, AE1/AE3 and EMA. Some cases are positive for P63, thrombomodulin and Uroplakin111. This tumour must be differentiated from metastatic malignancy to the bladder including pleomorphic giant cell carcinoma of the prostate. This tumor has a very poor prognosis. Patients often have advanced stage cancer at presentation.

Pleomorphic Rhabdomyosarcoma in upper limb in an adult

Rhabdomyosarcoma (RMS) is the most common form of soft tissue sarcoma in the first 2 decades of life, with a peak age incidence in very young children. Due to the rarity of adult RMS, information regarding its clinical and biologic characteristics is very limited. We report a case of pleomorphic RMS of upper extremity in a 50-year-old man. There was no metastasis of the tumor. The patient underwent surgery with enbloc excision of the tumor. Histopathological examination showed typical features of pleomorphic RMS composed of large polygonal pleomorphic cells with eosinophilic cytoplasm and plenty of large multinucleated tumor giant cells having bizarre nuclei. Postoperatively patient took radiotherapy. There was no recurrence of tumor with follow-up of 2 years.

Clear cell renal cell carcinoma with a syncytial-type multinucleated giant tumor cell component: implications for differential diagnosis

A component of syncytial-type multinucleated tumor giant cells is uncommon in clear cell renal cell carcinoma, and the histogenesis, incidence, and clinical implications of this finding are not well understood. We retrieved 13 such tumors from our pathology archives in patients with a median age of 60years, comprising 1.5% of clear cell renal cell carcinomas. Stage was typically pT4 or pT3 (each 38%). Microscopically, all tumors included a component of low-grade clear cell renal cell carcinoma with usual features. Syncytial-type giant tumor cells possessed voluminous cytoplasm, usually granular and eosinophilic, and numerous nuclei similar to those of the mononuclear tumor cells. Transition between areas of mononuclear and multinucleated cells was sometimes abrupt. Other findings included necrosis (77%), hyaline globules (46%), emperipolesis (46%), and intranuclear cytoplasmic invaginations (23%). Immunohistochemical staining typically revealed both mononuclear and multinucleated cells to be positive for carbonic anhydrase IX, CD10, epithelial membrane antigen, vimentin, and cytokeratin AE1/AE3 and negative for β human chorionic gonadotropin, TFE3, cathepsin K, cytokeratin 7, cytokeratin 20, HMB45, CD68, smooth muscle actin, and S100. Most patients with available information (7/9) were alive with metastatic disease at the most recent follow-up. Syncytial-type giant cells are an uncommon finding associated with aggressive clear cell renal cell carcinomas. Despite the unusual appearance of this tumor component, its immunoprofile supports an epithelial lineage and argues against trophoblastic, osteoclast-like, or histiocytic differentiation. Reactivity for typical clear cell renal cell carcinoma antigens facilitates discrimination from giant cells of epithelioid angiomyolipoma or other tumors, particularly in a biopsy specimen or a metastatic tumor.

Pleomorphic Dermal Sarcoma

The behavior of atypical fibroxanthoma is benign, if strict diagnostic criteria are applied. Tumors with similar pathologic features but deep subcutaneous invasion, necrosis, and/or lymphovascular or perineural invasion are thought to be associated with adverse outcome and are better regarded as pleomorphic dermal sarcoma or undifferentiated pleomorphic sarcoma of skin. This tumor group is not well documented in the literature, and its characteristics are only poorly defined. To study the clinical and pathologic spectrum more comprehensively, we retrieved 32 pleomorphic dermal sarcomas from our departmental files. The tumors were large (median: 25 mm) and exclusively presented on sun-damaged skin with a strong predilection for the head. Typically, elderly men were affected (median age: 81 y). Histologically, these often ulcerated tumors were poorly marginated, asymmetrical, and deeply invasive into deep subcutaneous, muscular, and/or fascial tissues. The tumors were cellular and composed of pleomorphic epithelioid cells, atypical spindle cells, and multinucleated tumor giant cells in varying proportions. Mitotic count was brisk and often atypical. Tumor necrosis was observed in 53%, lymphovascular invasion in 26%, and perineural infiltration in 29%. The majority of tumors showed a predominance of atypical spindle cells in a fascicular arrangement. A sheet-like growth of pleomorphic epithelioid cells or mixed spindle and epithelioid cell features were less frequently observed. Myxoid and keloidal change, a desmoplastic stromal response, pseudoangiomatous and storiform growth patterns, and admixed osteoclast-like giant cells were additional morphologic features in some cases. No immunoreactivity was noted for multiple cytokeratins, S100, HMB-45, desmin, and CD34. Smooth muscle actin was expressed in 70%, CD31 in 48%, epithelial membrane antigen in 16%, Melan A in 6%, and p63 in 1 case. CD10 was expressed in all cases stained. Follow-up (available for 29 patients; median: 24 mo) showed local recurrence in 28% and a metastatic rate of 10%, mainly in the skin. Progressive metastatic disease was observed in 2 patients. Remission was achieved in 1 patient using systemic chemotherapy. The second patient died in the setting of advanced-stage non-Hodgkin lymphoma. No disease-related mortality was noted. Our data underscore the importance of recognizing adverse histologic features in tumors otherwise resembling atypical fibroxanthoma. Deep subcutaneous invasion, tumor necrosis, and perineural and/or lymphovascular invasion confers at least low-grade malignant potential.