Giant Cell Morphology Research Articles

Clinicopathologic and Molecular Characterization of Xanthomatous Giant Cell Renal Cell Carcinomas: Further Support for a Close Morphologic Spectrum to Eosinophilic Solid and Cystic Renal Cell Carcinomas.

A recent study described a rare subtype of tuberous sclerosis complex ( TSC )-mutated renal cell carcinoma primarily characterized by Xanthomatous giant cell morphology. Only 2 cases in young individuals have been reported so far, making the correct diagnosis challenging from a pathological perspective. It remains unknown whether this tumor represents an independent subtype or belongs to other TSC -mutated tumors. We conducted a clinicopathologic evaluation and immunohistochemical profiling of 5 cases of Xanthomatous Giant Cell Renal Cell Carcinoma (XGC RCC) with confirmed TSC2 mutations through targeted DNA sequencing. In addition, we analyzed transcriptomic profiles using RNA-seq for the following samples: XGC RCC, Low-grade Oncocytic tumors (LOT), High-grade Oncocytic tumors/Eosinophilic Vacuolar Tumors (HOT/EVT), Eosinophilic Solid and Cystic Renal Cell Carcinomas (ESC RCC), Chromophobe cell Renal Cell Carcinomas (ChRCC), Renal Oncocytomas (RO), clear cell Renal Cell Carcinomas (ccRCC), and normal renal tissues. There were 2 female and 3 male patients, aged 22 to 58 years, who underwent radical nephrectomy for tumor removal. The tumor sizes ranged from 4.7 to 9.5cm in diameter. These tumors exhibited ill-defined boundaries, showed an expansive growth pattern, and featured distinctive tumor giant cells with abundant eosinophilic to Xanthomatous cytoplasm and prominent nucleoli. All tumors had low Ki-67 proliferation indices (<1%) and demonstrated immune reactivity for CD10, PAX8, CK20, CathepsinK, and GPNMB. Next-generation sequencing confirmed TSC2 mutations in all cases. RNA sequencing-based clustering indicated a close similarity between the tumor and ESC RCC. One patient (1/5) died of an accident 63 months later, while the remaining patients (4/5) were alive without tumor recurrences or metastases at the time of analysis, with a mean follow-up duration of 43.4 months. Our research supports the concept that Xanthomatous giant cell renal cell carcinoma (XGC RCC) shares clinicopathological and molecular characteristics with ESC RCC and shows a relatively positive prognosis, providing further support for a close morphologic spectrum between the two. We propose considering XGC RCC as a distinct subtype of ESC RCC.

A solitary giant cell tumor of the tendon sheath of left third finger in a 23-year-old man: a case report

Giant cell tumor of the tendon sheath (GCTTS) is a common condition usually encountered in middle aged men, usually seen on the thumb, index, middle fingers. These benign tumors are known to reoccur. Re-occurrence can be attributed to poor surgical technique, excision of the tumor in toto is considered difficult given the close proximity of the digital nerves, blood vessels, tendons to the tumor. A magnifying loop is usually used in these cases to identify and resect the satellite lesions. In this case report, we are presenting a case of solitary GCTTS of the tendon sheath in a 23-year-old man with history of gradually progressive painless swelling over his left third finger. Musculo-skeletal ultrasound revealed a heterogeneously hypo-echoic well-defined lesion over the ventral aspect of the left third finger. Histopathology showed giant cell morphology. Patient underwent exploration, tumor excision in toto with primary suturing in our institute with an uneventful postoperative period. No loss of range of movements of the PIP, DIP joints was noted in the postoperative period. Good dissection with excision of the tumor in toto gives better outcomes.

Xanthomatous Giant Cell Renal Cell Carcinoma: Another Morphologic Form of TSC -associated Renal Cell Carcinoma.

Over the past decade, several distinct novel renal epithelial neoplasms driven by underlying tuberous sclerosis comples ( TSC)/ mammalian target of rapamycin (MTOR) pathway mutations have been described. We report herein two distinctive TSC2 -mutated renal cell carcinomas which do not fit any previously described entity. The two renal carcinomas occurred in young patients (ages 10 and 31y), and were characterized by highly permeative growth within the kidney with metastases to perirenal lymph nodes. The neoplastic cells were predominantly large, multinucleated giant cells having variably eosinophilic to xanthomatous cytoplasm with basophilic stippling and frequent vacuolization. While the discohesive nature of the neoplastic cells, xanthomatous cytoplasm, immunoreactivity for histiocytic markers and minimal immunoreactivity for conventional epithelial markers raised the possibility of a histiocytic neoplasm, multifocal immunoreactivity for cytokeratin 20 helped establish their epithelial nature. Despite the aggressive growth pattern of these neoplasms and lymph node metastases, mitotic figures were rare and Ki-67 indices were low (<1%). One patient with follow-up shows no evidence of disease seven years after nephrectomy with no adjuvant therapy. Next-generation sequencing demonstrated TSC2 mutations in each case. By immunohistochemistry, downstream markers of mTOR pathway activation S6K1, 4EBP1, and glycoprotein nonmetastatic melanoma protein B were all highly expressed in these neoplasms, suggesting mTOR pathway activation as the neoplastic driver. While the cytokeratin 20 immunoreactivity and focal basophilic cytoplasmic stippling suggest a relationship to eosinophilic solid and cystic renal cell carcinoma, and cytoplasmic vacuolization suggests a relationship to eosinophilic vacuolated tumor, these neoplasms appear to be distinctive given their permeative growth patterns and predominant xanthomatous giant cell morphology. Addition of cytokeratin 20 to a panel of epithelial markers helps avoid misdiagnosis in such cases.

A RARE VARIANT OF SQUAMOUS CELL CARCINOMA: SARCOMATOID CARCINOMA

Background Sarcomatoid carcinoma (SC) is a rare variant of squamous cell carcinoma (SCC). It is a malignant tumor containing an SCC (in situ or invasive) component and a predominantly sarcomatous component with malignant spindle and/or pleomorphic cells. It accounts for less than 1% of all laryngeal tumors. Case Report An 8 × 5 mm polypoid lesion on the right vocal cord of a 72-year-old man with a history of smoking who presented with hoarseness was excised. In microscopic examination of the excision material, a tumoral lesion consisting highly pleomorphic cells with large nuclei and prominent nucleoli that had a spindle cell morphology in some places, an epithelioid cell morphology in some areas, and occasionally a giant cell morphology was observed. The tumor surface had an ulcerous appearance in most areas. There were typical and atypical mitoses in the tumor. Although squamous epithelium in intact benign appearance was in an area on the tumor surface, the presence of squamous epithelium containing atypical cells with disrupted organization standing apart from the tumor was remarkable. Immunohistochemical analysis revealed positive staining with smooth muscle actin and vimentin in the tumor cells. Multifocal positive staining with Pan-CK, EMA, and P40 was observed in the squamous epithelium and lesion. CD34 and desmin were negative. The case was reported to be compatible with SC. Conclusions SC is a rare variant of SCC. In the differential diagnosis, many tumors in spindle cell-like appearance such as nodular fasciitis, spindle cell melanoma, leiomyosarcoma, rhabdomyosarcoma, fibrosarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumors should be kept in mind and examined carefully. Sarcomatoid carcinoma (SC) is a rare variant of squamous cell carcinoma (SCC). It is a malignant tumor containing an SCC (in situ or invasive) component and a predominantly sarcomatous component with malignant spindle and/or pleomorphic cells. It accounts for less than 1% of all laryngeal tumors. An 8 × 5 mm polypoid lesion on the right vocal cord of a 72-year-old man with a history of smoking who presented with hoarseness was excised. In microscopic examination of the excision material, a tumoral lesion consisting highly pleomorphic cells with large nuclei and prominent nucleoli that had a spindle cell morphology in some places, an epithelioid cell morphology in some areas, and occasionally a giant cell morphology was observed. The tumor surface had an ulcerous appearance in most areas. There were typical and atypical mitoses in the tumor. Although squamous epithelium in intact benign appearance was in an area on the tumor surface, the presence of squamous epithelium containing atypical cells with disrupted organization standing apart from the tumor was remarkable. Immunohistochemical analysis revealed positive staining with smooth muscle actin and vimentin in the tumor cells. Multifocal positive staining with Pan-CK, EMA, and P40 was observed in the squamous epithelium and lesion. CD34 and desmin were negative. The case was reported to be compatible with SC. SC is a rare variant of SCC. In the differential diagnosis, many tumors in spindle cell-like appearance such as nodular fasciitis, spindle cell melanoma, leiomyosarcoma, rhabdomyosarcoma, fibrosarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumors should be kept in mind and examined carefully.

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.

Driving Solar Giant Cells through the Self-organization of Near-surface Plumes

Abstract Global 3D simulations of solar giant-cell convection have provided significant insight into the processes which yield the Sun’s observed differential rotation and cyclic dynamo action. However, as we move to higher-resolution simulations a variety of codes have encountered what has been termed the convection conundrum. As these simulations increase in resolution and hence the level of turbulence achieved, they tend to produce weak or even anti-solar differential rotation patterns associated with a weak rotational influence (high Rossby number) due to large convective velocities. One potential culprit for this convection conundrum is the upper boundary condition applied in most simulations, which is generally impenetrable. Here we present an alternative stochastic plume boundary condition which imposes small-scale convective plumes designed to mimic near-surface convective downflows, thus allowing convection to carry the majority of the outward solar energy flux up to and through our simulated upper boundary. The use of a plume boundary condition leads to significant changes in the convective driving realized in the simulated domain and thus to the convective energy transport, the dominant scale of the convective enthalpy flux, and the relative strength of the strongest downflows, the downflow network, and the convective upflows. These changes are present even far from the upper boundary layer. Additionally, we demonstrate that, in spite of significant changes, giant cell morphology in the convective patterns is still achieved with self-organization of the imposed boundary plumes into downflow lanes, cellular patterns, and even rotationally aligned banana cells in equatorial regions. This plume boundary presents an alternative pathway for 3D global convection simulations where driving is non-local and may provide a new approach toward addressing the convection conundrum.

Histologic spectrum and molecular subgroups of ependymal tumors

Ependymal tumors are relatively infrequent neuroepithelial neoplasms, but they have a wide and complex histologic spectrum including subtypes and variants recognized by the current Word Health Organization (WHO), and some special morphologic variants or growth patterns such as giant cell morphology, melanin differentiation, signet - ring, fat or vacude metaplasia, cartilage metaplasia with or without bone formation, oncocytic, epithelioid, and so on. Pathologists need to pay attention to identification and differential diagnosis of these special morphologic variants. Genomic and DNA methylation profiling studies have defined nine distinct molecular subgroups of ependymal tumors. RELA fusion - positive ependymoma has now been designated as one of the distinctive molecular variants of ependymoma by 2016 WHO classification of central nervous system tumors. Risk stratification by molecular subgrouping is superior to histological grading. However, how to integrated molecular genetic features into the histological spectrum need to be further researched. DOI: 10.3969/j.issn.1672-6731.2017.10.002

The plant cell inhibitor KRP6 is involved in multinucleation and cytokinesis disruption in giant-feeding cells induced by root-knot nematodes

The plant cell cycle inhibitor gene KRP6 has been investigated in roots infected by plant-parasitic root-knot nematodes (Meloidogyne spp.). Unexpectedly, KRP6 overexpressing lines revealed a distinct role for this specific KRP as an activator of the mitotic cell cycle. This function was confirmed in Arabidopsis thaliana suspension cultures ectopically expressing KRP6. A blockage in the mitotic exit was observed in cell suspensions and in giant cells resulted in the appearance of multi-nucleated cells. KRP6 expression during nematode infection and the similarity in phenotypes among KRP6 overexpressing cell cultures and giant-cell morphology strongly suggest that KRP6 is involved in multinucleation and acytokinesis occurring in giant-cells. Once again nematodes have been shown to manipulate the plant cell cycle machinery in order to promote gall establishment.

GIANT CELLS AND GIANT CELL LESIONS OF ORAL CAVITY- A REVIEW

Giant cells are large mononucleated or multinucleated cells that are seen in a variety of physiological as well as pathological conditions. Multinucleated giant cells (MGCs) are important mediators of tissue remodeling and repair and also for removal of foreign materials and various pathogens. The commonly encountered giant cells arise from monocyte precursors, formed due to different mechanisms. Depending upon the mechanism of their formation these cells assume distinctly variable phenotypes. The giant cell lesions of oral cavity have been classified on the basis of etio-pathogenesis, the presence of which at times being pathognomic. We attempt to review the basic information regarding the mechanism of formation and morphology of giant cells and its significance in the associated giant cell lesions. Also we have tried to describe the clinical, histopathological and immunohistochemical aspects of various giant cell lesions of the oral cavity.

Knocking-down Meloidogyne incognita proteases by plant-delivered dsRNA has negative pleiotropic effect on nematode vigor.

The root-knot nematode Meloidogyne incognita causes serious damage and yield losses in numerous important crops worldwide. Analysis of the M. incognita genome revealed a vast number of proteases belonging to five different catalytic classes. Several reports indicate that M. incognita proteases could play important roles in nematode parasitism, besides their function in ordinary digestion of giant cell contents for feeding. The precise roles of these proteins during parasitism however are still unknown, making them interesting targets for gene silencing to address protein function. In this study we have knocked-down an aspartic (Mi-asp-1), a serine (Mi-ser-1) and a cysteine protease (Mi-cpl-1) by RNAi interference to get an insight into the function of these enzymes during a host/nematode interaction. Tobacco lines expressing dsRNA for Mi-ser-1 (dsSER), Mi-cpl-1 (dsCPL) and for the three genes together (dsFusion) were generated. Histological analysis of galls did not show clear differences in giant cell morphology. Interestingly, nematodes that infected plants expressing dsRNA for proteases produced a reduced number of eggs. In addition, nematode progeny matured in dsSER plants had reduced success in egg hatching, while progeny resulting from dsCPL and dsFusion plants were less successful to infect wild-type host plants. Quantitative PCR analysis confirmed a reduction in transcripts for Mi-cpl-1 and Mi-ser-1 proteases. Our results indicate that these proteases are possibly involved in different processes throughout nematode development, like nutrition, reproduction and embryogenesis. A better understanding of nematode proteases and their possible role during a plant-nematode interaction might help to develop new tools for phytonematode control.

Correlation of histopathologic features with demographic, gross and radiographic findings in giant cell granulomas of the jaws.

Background and aims. The correlation between morphology of giant cells in peripheral granulomas of the jaws and the aggressive behavior of the lesion is unknown. This study investigated the correlation between the histopathologic features with demographic, gross and radiographic findings in giant cell granulomas. Materials and methods. In this analytical study, data from 23 cases of central giant cell granuloma (CGCG) and 42 cases of peripheral giant cell granuloma (PGCG) were analyzed, focusing on age, gender, location, and gross and radiographic features. For each patient, microscopic slides were assessed in terms of histologic features of giant cells and stroma. Results. No significant differences were found in the mean number of nuclei or the size of nuclei and giant cell distribution patterns between the jaws and genders in both lesions (P >0.05). Correlation between the mean number of nuclei and age was positively significant and correlation between the size of nuclei and age was negatively significant (P < 0.05). In addition, correlation between the mean number and size of nuclei and the size of the lesion was significant (P < 0.05). Correlation between stroma and aggressiveness of CGCGs was not statistically significant. Correlation between histopathologic features and radiographic findings was not statistically significant (P > 0.05). Conclusion. There were correlations between the mean number of nuclei per giant cell and the size of the lesion and age, and between the size of nuclei and size of the lesion. No relation was observed between histopathologic and radiographic features.

Induction of a trophoblast-like phenotype by hydralazine in the p19 embryonic carcinoma cell line

Chemicals that affect cellular differentiation through epigenetic mechanisms have potential utility in treating a wide range of diseases. Hydralazine decreases DNA methylation in some cell types but its effect on differentiation has not been well explored. After five days of exposure to hydralazine, P19 embryocarcinoma cells displayed a giant cell morphology and were binucleate, indicative of a trophoblast-like morphology. Other trophoblast-like properties included the intermediary filament Troma-1/cytokeratin 8 and the transcription factor Tead4. A decrease in CpG methylation at three sites in the TEAD4 promoter and the B1 repeated sequence was observed. Knocking down expression of Tead4 with siRNA blocked the increase in Troma-1/cytokeratin 8 and over expression of Tead4 induced the expression of Troma-1/cytokeratin 8. Cells treated for 5days with hydralazine were no longer capable of undergoing retinoic acid-mediated neuronal differentiation. An irreversible loss of the pluripotent transcription factor Oct-4 was observed following hydralazine exposure. In summary, hydralazine induces P19 cells to assume a trophoblast-like phenotype by upregulating Tead4 expression through a mechanism involving DNA demethylation.

Giant cell tumor of soft tissue: Cytological diagnosis of a case

Giant cell tumors of soft tissue (GCT-STs) are rare neoplasms and are mainly seen in adults and in the elderly population, usually in the extremities. When evaluated along with clinical features, the cytological features are sufficient to distinguish GCT-STs from other more common tumors with giant cell morphology. We report here a case of a giant cell tumor of soft tissue diagnosed on the basis of fine needle aspiration cytology and confirmed after histopathology.

Primary giant cell tumor of soft tissue in the finger

Primary giant cell tumor of soft tissue (GCTST) arising in a finger is a rare event. We report a case of a 54-year-old man with a primary finger giant cell tumor that appeared histologically identical to giant cell tumor of bone. The patient presented with a cystic mass of the finger. The magnetic resonance imaging showed no relation between the nodule and bone, tendons or synovial tissues. The distinction of this entity from other more common primary finger tumors with giant cell morphology is emphasized.

IFPA Award in Placentology Lecture – Characteristics and Significance of Trophoblast Giant Cells

Extraembryonic development in rodents depends on the differentiation and function of trophoblast giant cells. Morphologically striking, giant cells exhibit many extraordinary characteristics adapted to ensure the success of pregnancy. This review summarizes some of the intriguing aspects of giant cell morphology and function. Giant cells are highly polyploid as a result of a switch from a mitotic to an endoreduplicative cell cycle. They further partition their genome content into various fragments which may represent a mechanism to maximize protein synthesis. Similar to metastatic tumour cells, they breach basement membranes and invade deeply into a foreign tissue, the maternal decidualized uterine stroma. Their angiogenic and vasodilatory properties, combined with the ability to remodel arterial walls, enable them to redirect maternal blood flow towards the implantation site. Recent advances have recognized that the giant cell population is more diverse than previously recognized and future studies will have to show how these subtypes differ functionally and how their differentiation is controlled.

Giant cell tumor of soft tissue arising in breast

Primary giant cell tumor of soft tissue (GCT-ST) arising in breast is exceedingly rare. We report a case of a 60-year-old woman with a primary breast giant cell tumor that appeared histologically identical to giant cell tumor of bone and had a clinically malignant course. The patient presented with a cystic mass of the breast, suspected on imaging to be an organizing hematoma, possibly related to previous injury. Histopathological evaluation revealed a neoplasm composed of mononuclear cells admixed with osteoclast-like giant cells resembling giant cell tumor of bone. Immunohistochemical staining was positive for CD68, smooth muscle actin, and vimentin, but was negative for a panel of epithelial and additional muscle markers. These features were most consistent with GCT-ST, an uncommon neoplasm of low malignant potential. Despite aggressive surgical treatment achieving clear surgical margins, the patient expired with pulmonary metastases within a year of her initial presentation. This case demonstrates the difficulty of predicting clinical behavior of GCT-ST of breast on the basis of histological features and depth of tumor alone. To our knowledge, this is the first case report of a GCT-ST arising in the breast associated with a fatal outcome. The distinction of this entity from other more common primary breast tumors with giant cell morphology is also emphasized.

Severe Feto-Placental Abnormalities Precede the Onset of Hypertension and Proteinuria in a Mouse Model of Preeclampsia1

Preeclampsia is a prevalent and potentially devastating disorder of pregnancy. Characterized by a sudden spike in blood pressure and urinary protein levels, it is associated with significant obstetric complications. BPH/5 is an inbred mouse model of preeclampsia with borderline hypertension before pregnancy. BPH/5 mice develop hypertension, proteinuria, and endothelial dysfunction during late gestation (after E14.5). We hypothesized that BPH/5 mice might exhibit early feto-placental abnormalities before the onset of maternal disease. All placental cell lineages were present in BPH/5 mice. However, the fetal and placental weights were reduced, with abnormalities in all the placental zones observed starting early in gestation (E9.5-E12.5). The fractional area occupied by the junctional zone was significantly reduced at all gestational timepoints. Markedly fewer CDKN1C-stained trophoblasts were seen invading the proximal decidual zone, and this was accompanied by reductions in Cdkn1c gene expression. Trophoblast giant cell morphology and cytokeratin staining were not altered, although the mRNA levels of several giant cell-specific markers were significantly downregulated. The labyrinth layer displayed decreased branching morphogenesis of endothelial cells, with electron microscopy evidence of attenuated trophoblast layers. The maternal decidual arteries showed increased wall-to-lumen ratios with persistence of actin-positive smooth muscle cells. These changes translated into dramatically increased vascular resistance in the uterine arteries, as measured by pulse-wave Doppler. Collectively, these results support the hypothesis that defects at the maternal-fetal interface are primary causal events in preeclampsia, and further suggest the BPH/5 model is important for investigations of the underlying pathogenic mechanisms in preeclampsia.

Computerized video time-lapse (CVTL) analysis of the fate of giant cells produced by X-irradiating EJ30 human bladder carcinoma cells.

This study was designed to examine the viability and proliferation of uninucleated and multinucleated giant cells formed after 6 Gy X irradiation. The pedigrees of 102 individual EJ30 giant cells present 5 days after irradiation were analyzed from time-lapse movies captured over 6.3 days from 100 fields (100x). Pedigree analysis enabled us to study the proliferation of giant cells. The average starting size (area) of the giant cells (14500 +/- 9100 microm(2)) was approximately 25 times larger than the normal-sized cells observed after irradiation (560 +/- 200 microm(2)). From a total of 76 pedigrees of uninucleated giant cells, 42 had giant cells that either died or were arrested, while 34 divided at least once and produced progeny that divided again (five three times and three four times) before the progeny died or were arrested. Twenty-four pedigrees contained progeny that were lost from observation after dividing at least once. While most progeny continued to have giant cell morphology, two uninucleated giant cells ultimately produced progeny that contained two normal-sized cells. From a total of 26 multinucleated giant cells, only three divided. Two divided only once, but one produced progeny that divided two times. In all, 37 out of 102 giant cells divided at least once; eight of these divided four or five times with two of these pedigrees ultimately producing two normal-sized daughter cells. These results suggest that a small fraction of giant cells might be potentially clonogenic.

Expression of gelatinase B in trachomatous conjunctivitis

BACKGROUND/AIMSGelatinase B is a matrix metalloproteinase involved in extracellular matrix (ECM) breakdown often associated with scarring and other pathological disorders. It was investigated whether gelatinase B is involved in the...

Gelatinase B in chronic synovitis: immunolocalization with a monoclonal antibody.

Gelatinase B is a matrix metalloproteinase (MMP-9) involved in the remodelling of extracellular matrices of connective tissues. With the use of specific monoclonal antibodies against human gelatinase B, the producer cell types were pinpointed in histopathological sections of a number of arthritic diseases. In cases of acute joint trauma, chondromatosis, villonodular synovitis and a cyst of a bursa, high numbers of strongly immunopositive neutrophils were observed in addition to weaker staining macrophages. Activated macrophages with giant cell morphology clearly stained with the gelatinase B-specific monoclonal antibody in the case of villonodular synovitis and in an epidermoid cyst. However, in the sections from patients with rheumatoid arthritis, no immunostaining was seen. In other cases of chronic synovitis, however, within the lymphocyte nodular aggregates a strong gelatinase B expression was observed in morphologically identified dendritic cells. In conclusion, gelatinase B production in joint disease seems to be predominantly by neutrophils and cell types of the macrophage/antigen-presenting cell lineage.