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1.  Subcutaneous Dermatofibroma: A Rare Case Report with Review of Literature 
A purely Sub-cutaneous benign fibrous histiocytoma (BFH; dermatofibroma) is rarely reported, as it is usually a dermally located mesenchymal tumour and in absence of supportive immunohistochemical (IHC) studies, it is often misdiagnosed. We are describing a case of a 19-year-old female who presented to the skin outpatient department with a painful swelling on the medial side of her thigh. Fine needle aspiration (FNA) revealed a sub-cutaneous spindle cell (mesenchymal) lesion which was corroborated on histopathology, with differentials of BFH and dermatofibrosarcoma protruberans (DFSP). BFH constitutes a diagnostic dilemma for both clinicians and pathologists, because the lesions share common clinical symptoms, radiological characteristics and histological features with many varied entities. For its subtyping and confirmation; immunohistochemical (IHC) studies were undertaken. In the present case, positivity of IHC markers, vimentin and smooth muscle actin emphatically proved that BFH arose exclusively from the subcutaneous region, with no dermal origin. Also, a negative CD34 immunostaining, along with low B-cell lymphoma 2 (Bcl-2) expression ruled out DFSP (both are strongly expressed in DFSP), MFH and other malignant mesenchymal lesions. Negative CD 68 staining ruled out giant cell lesions and their congeners. This case is worth reporting, as it not only describes a rare case presentation of BFH, but as it also highlights the importance of IHC, thus helping to comprehensively clinch the diagnosis by systematically ruling out other differentials.
PMCID: PMC4064913  PMID: 24959453
Subcutaneous; Benign fibrous histiocytoma; Immunohistochemistry
From the foregoing description of the histological changes in the leptomeninx it is quite evident that we are dealing with a chronic, stationary, healing form of tuberculous inflammation. This statement is substantiated, in the first place, by the clinical history. The only reasonable interpretation of the symptoms would establish the duration of the process as four months. The imaginable contingency that there existed first a meningeal syphilitic lesion that was dispersed by the iodide of potassium only to be followed by a tuberculous infection is so remote and unlikely that it need not be discussed. At all events the tuberculous leptomeningitis, which presented a typical distribution, began insidiously, existed at times in a latent condition, and pursued a very anomalous course, marked by a relative mildness of all the symptoms, and thus it came about that when an apparent or real improvement followed the administration of iodide of potassium able observers were induced to make an erroneous diagnosis. Death occurred as a result of an intercurrent infection. The long duration of the process is also shown, anatomically, by the thick layer of firm, translucent and gelatinous material that matted together the structures at the base, and also by the evident adhesions between the pia and the brain. The histological examination furnishes proof positive of the correctness of the conclusion in regard to the peculiar character of this process because it shows: (1) That the tuberculous proliferation is uniform in development and has reached nearly the same stage of evolution throughout the entire extent of the leptomeninx involved; it is not a process that has advanced by exacerbations and irregular extensions; the lesions are, generally speaking, of nearly the same age everywhere and must have begun at about the same time. (2) That only a very limited degree of caseous degeneration is present, pointing to an early arrest of the activity of the tubercle bacillus or to a very decided diminution or attenuation of its virulence. (3) That the subendothelial intimal proliferations of epithelioid cells, so generally found in acute tuberculous leptomeningitis,* have in this case become more or less completely changed into distinct fibrous tissue in which but very slight, if any, direct evidence of its tuberculous origin can be found. It is only by recognizing that the chronic endarteritis is most marked in correspondence with the most advanced adventitial tuberculous changes, and by finding an imperfect, much altered giant cell in one district of intimal thickening, that we were able to establish the direct kinship of the endovascular changes with those of the pia in general. (4) That acute inflammatory changes, in the form of emigration of polymorphonuclear leucocytes and of fibrinous exudation, are entirely absent in all parts of the district involved. The presence of a turbid serous fluid is of course not at all inconsistent with the view that the anatomical changes are of long duration. (5) That the granulation tissue present is, in general, undergoing fibrillation and contains a rich supply of enabryonal capillary vessels as well as of larger blood-vessels of evidently new formation. The absence of any considerable extent of polymorphonuclear leucocytic infiltration in this tissue has already been referred to. The cells in the granulation tissue correspond to the cells of embryonal or formative connective tissue. Vacuolation is rarely present. (6) That the unusually large number of giant cells present are remarkably free from evidences of necrosis and degeneration of the character ordinarily observed in tuberculous proliferations, that they do not contain in demonstrable form tubercle bacilli, and that the majority of the giant cells seem to be separating into individual cells and smaller masses often with, but sometimes also without, evidences of nuclear disintegration. The possibility that these phenomena may signify fusion instead of the sundering of cells will be discussed below. For these reasons there can be no doubt that the general claim that we are dealing with an instance of chronic, healing tuberculous meningitis must be regarded as established beyond dispute. The growth of tubercle bacilli in the glycerine-agar tubes, inoculated with the fluid from the pial meshes, and the demonstration of tubercle bacilli, though in very small numbers, between the cells of the embryonal tissue, furnish the positive evidence that we are actually dealing with a tuberculous process due to living and not to dead bacilli. The degree of virulence of the cultures of tubercle bacilli was, unfortunately perhaps, not studied. The presence of living tubercle bacilli in a tissue free from active and acute changes characteristic of tuberculosis demonstrates that, whatever the actual degree of virulence of the bacilli may have been, the tissue in which they were found was at this time relatively immune from their action. The manner in which this immunity was produced, and in which the process of healing was initiated, need not be discussed at this time any further than to again direct attention to the fact that the bacilli lost their virulency as regards the cells in this leptomeninx before these cells underwent any marked degree of degeneration. The cells of the tuberculous proliferations survived the further action of the bacilli whose original effect it was to initiate cell accumulation or proliferation; the cells also retained sufficient vitality to develop, in some instances at any rate, into formative cells according as their origin would dictate, e. g. into fibroblasts. That fibroblasts are formed only by embryonal connective tissue cells, and not by wandering cells, such as the large mononuclear leucocytes, we are well aware, is possibly still a disputable assumption, and we do not consider it pertinent to discuss the question any further in connection with this study, but would only emphasize the point that some of the cells of tuberculous proliferations may, under favorable circumstances, become formative cells, and, furthermore, that the amount of formative tissue produced may be far in excess of what is actually needed for purposes of repair only. Surely the appearances here noted indicate that the bacillus of tuberculosis has the power to stimulate fixed cells to multiply, unless one assumes that all, or almost all, the formative cells here seen are derived from wandering cells attracted by the presence of the bacillus and its products. As to the ultimate fate of the formative and other cells in this healing tuberculous tissue no final statements can be made. It must be remembered that it is only one stage in the process of healing that is dealt with. The well marked evidences of fibrillation, the quite extensive formation of new vessels, the absence of evidences of degenerative changes in the uninuclear cells, all point to the production of new fibrous tissue as sure to occur, but it seems quite probable that occasional epithelioid cells may undergo or have undergone dropsical or other forms of degeneration, although it is certainly apparent that so far as the small cells are concerned the involution of the tuberculous tissue is not occurring through disintegration. Perhaps the most interesting feature in this case is the opportunity it affords to study the changes in the giant cells of healing, non-degenerated tuberculous tissue. In the first place, the large number of giant cells is quite remarkable. The general characters of the tissue in which they are found recall the fact that giant cells are regarded as quite constant elements in chronic mild tuberculosis; often the giant cells are the only cells that contain bacilli (Koch). In this instance the giant cells do not contain bacilli that are demonstrable by the usual methods; neither do they contain bodies that can be definitely interpreted as degenerate forms of bacilli such as those found by Metchnikoff, Stchastny, Weicker, and others, in the giant cells of Spermophilus guttatus, in avian and in human tuberculosis. Metchnikoff states, however, that he knows of the occurrence of such degenerate forms only in the Spermophilus guttatus under the circumstances mentioned, and in the rabbit and guinea-pig in mammalian tuberculosis, but not in man; consequently, the manner in which the giant cells rid themselves of the bacilli undoubtedly present in their interior at some time during their existence, must as yet remain without any explanation. In the description of the histological changes the various appearances presented by the giant cells are described somewhat minutely. The essential observations made concern, in my opinion, the further fate of giant cells which are still found to persist in healing nondegenerated tuberculous tissue. It was, I believe, quite conclusively shown that the consecutive changes appear to consist in the breaking up of the nuclei, the removal of the detritus by phagocytes, and the formation of a few apparently viable uninuclear cells in the case of more degenerated, exhausted giant cells, while other, and, as it would seem, better preserved or younger giant cells, separate into a number of individual, uninuclear cells with but little or no nuclear disintegration. Objection might be raised to this interpretation of the appearances in the giant cells. While no one could very well dispute the view that part of the giant cells are undergoing retrogressive and absorptive changes with the production of some viable cells, a question might well be raised concerning the nature of the process taking place in those giant cells that have been spoken of as splitting up or dividing into uninuclear cells and smaller multinucleated masses without much evidence of nuclear disintegration. It might be claimed that the process is one of fusion of many cells to form giant cells, and not one of division of fully formed giant cells into small cells. But a broad view of the processes described speaks against fusion. In the first place we are not dealing with a stage of tuberculous proliferation (Baumgarten), or cell accumulation (Metchnikoff), in which one would look for the production of giant cells, no matter which view concerning the histogenesis of tubercle be assumed as the correct one, because it has been demonstrated that, from whichever point of view the lesions are examined, the same positive conclusion that they are in the process of healing is reached; there is, therefore, no occasion for the formation of new giant cells in such wide-spread degree throughout the district involved. It might he claimed that the cells became arrested and, as it were, fixed in the act of fusion which was taking place in the early stage of the meningitis, but it would be difficult to understand the nature of the stimulus that could hold the cells together in such a peculiar manner for such a long time. It must be remembered that bacilli or bacillary detritus could not be found among the incomplete or in the complete giant cells. In the second place the difference between the cells that are undergoing disintegration and those regarded as dividing is essentially, to a certain extent at any rate, one of degree, because in the first instance there is not much, if any, doubt but that viable smaller cells are also formed, and in the second instance some, though often very slight, evidence of nuclear fragmentation is nearly always present; it would also be correct to infer that in advanced subdivision of a giant cell much, and perhaps all, of the nuclear detritus produced might have been removed up to the last trace; finally, the two extremes of these changes in the giant cells are connected by transition stages passing by gradation from the one to the other. Hence it is justifiable to conclude, for the time being, that in healing non-degenerated tuberculous tissue, the multinucleated giant cells may in part disintegrate and undergo absorption, in part form viable small cells; that both these changes may, and usually do, affect the same cell, but that in one class of cells—presumably the older or the more exhausted—the retrogressive process is predominant, while in a second class of cells—presumably the young and vigorous—the progressive changes are the more marked. In this connection it may be pointed out that while there cannot very well be any question but that we are dealing only with dividing and not coalescing cells, yet if this conclusion should be disputed and found incorrect, then the only remaining alternative would be to infer that this tissue furnished a unique and striking example of the formation of plasmodial masses by fusion in human tuberculosis, a conclusion to which many pathologists would refuse to subscribe, if for no other reason than because it is not in accordance with the almost universally accepted teachings of Baumgarten and Weigert in regard to the mode of formation of the giant cells in tuberculosis. Believing as I do that the giant cells under consideration are in the act of division and not at all of fusion, there remain to be discussed some of the histological and other features presented by the dividing cells. Many of the giant cells, perhaps the majority, contain larger and smaller vacuoles in the protoplasm. The exact significance of this vacuolation is not always clear. When the vacuolation accompanies an evident solution of the nucleus (karyolysis), there cannot be any doubt but that we are in the presence of a distinctly retrogressive process. Vacuoles are also most numerous in the giant cells that present other evidences of degeneration, such as coarseness of the granules in the protoplasm and extensive nuclear disintegration, but they occur as well around nuclei that stain deeply, around cells that seem to be separating from the giant cell, and even about nuclei that present mitoses. The formation of vacuoles seems to be responsible, to a certain extent at any rate, for the diminution in the volume of disintegrating and dividing giant cells, as shown by the clear spaces that form about them; these spaces are too large and occur too uniformly to be attributed solely to artificial shrinking produced by the hardening in alcohol. Further undoubted evidence of retrogression in certain giant cells is the occurrence of nuclear disintegration, or karyorhexis, which sets free larger and smaller chromatin masses that are recognized in the giant cell as well as in the interior of the phagocytes usually found around such cells. Almost all the polymorphonuclear leucocytes found in this tissue are met with around giant cells with broken-up nuclei. In many nuclei of disintegrating giant cells can be noted appearances that correspond well to certain stages in the complicated karyorhexis observed in anæmic necrosis by Schmaus and Albrecht; some of the nuclei with budding processes correspond particularly well with those in certain of their drawings; the interior of giant cells of tuberculous tissue may, it would seem, present conditions favorable to the development of this series of postnecrotic nuclear change. Vacuolation, karyolysis and karyorhexis are the essential steps that lead to destruction of the whole or parts of some of the giant cells; associated with these processes there is usually observed a splitting up of the body of the giant cell into irregular fragments with as well as without nuclei; and, as described, more or less phagocytosis of the resulting remnants of various kinds is seen. But evident degenerative and necrotic processes in a giant cell may be associated with progressive changes. While some nuclei undergo vacuolation or break up, others seem to become richer in chromatin and to stain more deeply at the same time that they seem to acquire cell bodies quite distinct from the protoplasm of the giant cells: this hyperchromatosis does not, therefore, seem to be a stage in karyorhexis. A very few but undoubted karyokinetic figures were found, together with evidences of division of the cell body formed in the giant cell protoplasm. Precisely similar changes are described by Klebs in healing pulmonary tuberculosis of the guinea-pig; the nuclei of the giant cells became rich in chromatin and karyokinetic figures occurred. Krückmann among others has found occasional mitoses in giant cells around foreign bodies, as well as elsewhere, but it would seem that such mitoses have always been interpreted as indicating the probable mode of formation of the giant cells rather than of their involution. The question of mitosis in existing multinucleated cells has recently been studied by Krompecher, who concludes that the individual nuclei of such cells may undoubtedly divide by mitosis, either simultaneously or at separate times. Division by amitosis can also occur, but mitosis is the only progressive form of division, amitosis being a retrogressive, disintegrating process that must be looked upon as an evidence of degeneration of the nucleus. Ziegler states that in division of giant cells whose nuclei have multiplied by mitosis it may happen that the separating cell remains enclosed in the protoplasm of the mother cell. A singular phase in the involution of the giant cells in this pia is to be found in the existence of progressive changes side by side with nuclear necrosis and with degeneration; this finding indicates that giant cells may contain many independent elements which, though apparently fused into one large cell, may preserve their individuality so that while some nuclei die, others proliferate and perhaps feed on the remnants of their dead brethren and form new, viable small cells. The nuclei in giant cells may be looked upon as representing independent centres, capable at times of existing even though the cell protoplasm is disintegrated. Many of the giant cells separate into individual cells, unaccompanied or unassociated with much evidence of necrosis. These cells may be regarded as the more vigorous forms. Here also are observed occasional mitoses—but on the whole extremely few—and very constantly an evident increase in the amount of chromatin in the nuclei of the new cells as compared with the amount ordinarily found in the nuclei of giant cells. These deductions concerning the persistence of the vitality of some of the nuclei, even in the presence of molecular and morphological changes in the cytoplasm and in other nuclei of the giant cell that lead to disintegration, are not entirely without the support of previous observations on cells, which, although made under different conditions, are nevertheless, it would seem, applicable to cells in general. Thus the brilliant investigations of Loeb upon the effects of various unfavorable surroundings, such as absence of oxygen or reduction of the amount of water, upon the cleavage of eggs of many kinds, show that the conditions which arrest development are qualitatively alike for nucleus and protoplasm, but quantitatively less for the protoplasm; when the irritability of the protoplasm is suspended the nucleus may segment without segmentation of the protoplasm, but upon re-establishment of favorable conditions the protoplasm may divide into about as many spheres as there are nuclei preformed—the nucleus persists, preserves the irritability of the cell and stimulates the protoplasm to segmentation. From the appearances of the giant cells here described it would seem, then, that some nuclei are able to maintain their vitality longer than others in the same cell, and under certain conditions to stimulate parts of the protoplasm to segment; in other cells all the nuclei have, as a rule, preserved their irritability. The groups of cells formed by the dividing of the giant cells can be traced by studying the process at the different stages in the different parts of the tissue. They assume an oval or spindle-shaped form, becoming more and more like the formative and endothelioid cells of young connective tissue, but their ultimate fate cannot be determined because it concerns essentially only one limited period in the involution of the tissue. It may be said with reasonable certainty, however, that the new cells do not form blood-vessels, but as regards their forming lymph-vessels nothing definite can be concluded. It would not be safe to draw any definite conclusions, from the appearances described, with regard to the origin and the mode of formation of the giant cells. The resulting small cells in general resemble very much endothelial and formative cells, but some of them are, at certain stages at any rate, not unlike large mononuclear leucocytes; their final fully developed or mature condition being unknown, no positive inference can be drawn as to their pre-giant-cell origin. The evidence points to the fact that the most probable origin of the giant cells, as indicated by their form and the apparent future career of their descendants, would be the fixed mesoblastic cells of the pia. In regard to the mode of formation of the giant cells it is quite clear that it must involve some process which is not incompatible with the viability of the small cells which may spring from the giant cells. Whether this would speak more in favor of formation by fusion than by karyokinesis of a single cell without division of the cell body cannot be well determined, and as long as authors are not agreed upon the question of the production of living, procreative cells by amitosis (direct segmentation, direct and indirect fragmentation) it would not be profitable to discuss the compatibility or incompatibility of the views of those investigators who trace the origin of giant cells to amitotic division, with the progressive changes that giant cells have been shown to be capable of. The fact that giant cells in tuberculous tissue, under certain conditions, undergo progressive changes and separate into small, living cells proves that they are not, as claimed by Baumgarten, Weigert and others, necrobiotic elements that are doomed to destruction from their very inception. On the other hand it lends more strength, if that were necessary, to the teleological view urged by Metchnikoff that they are living, defensive cells (whatever their origin may be), formed for the distinct purpose, like plasmodial masses in general, of isolating and removing foreign, harmful bodies, in this case the tubercle bacillus, and, having accomplished their object without being destroyed or exhausted, or the cause of their formation being removed or neutralized in some way, they, or their nuclei, may retain enough irritability to form a larger or smaller number of living, small, uninuclear cells.
PMCID: PMC2117963  PMID: 19866866
3.  Intra-articular Nodular Fasciitis: An Unexpected Diagnosis for a Joint Lesion: A Case Report 
Malaysian Orthopaedic Journal  2014;8(2):63-65.
Pathological lesions in and around a joint can arise from underlying dermis, subcutis, deep muscle, bone or synovium. Clinical presentation can include joint pain, joint swelling, palpable masses and mechanical restriction. Whilst giant cell tumour of tendon sheath, pigmented villonodular synovitis, synovial chondromatosis, lipoma arborescens, juxta articular myxomas and inflammatory arthritis are the better-known conditions of the joint. Intra-articular nodular fasciitis, on the other hand, is less well recognized both clinically and radiologically. It is rarely seen in routine practice and is only described in case reports in the literature. Due to the non-specific clinical and radiological findings as well as the unfamiliarity with the entity, the diagnosis of intra-articular nodular fasciitis is usually clinched only after histological examination. We present a case of intra-articular nodular fasciitis arising in the knee joint which was not suspected clinically or radiologically.
Key Words
Intra-articular, nodular fasciitis, joint, knee, MRI
PMCID: PMC4181075  PMID: 25279098
4.  Giant cell tumour of tendon sheath of the digits. A systematic review 
Hand (New York, N.Y.)  2011;6(3):244-249.
We reviewed the literature to evaluate the demographic, clinical and histological profile of giant cell tumour of tendon sheath of the digits (GCTTSD). The overall recurrence rate and the factors affecting tumour recurrence were also assessed.
We searched for published articles regarding the GCTTSD in the English literature the last 30 years using the PubMed search engine. All retrieved papers were analysed and their reference lists were also screened if relevant. Clinical studies with less than five patients and follow-up less than 2 years were excluded from further evaluation. For each report, information was gathered related to trial characteristics and study population. Location and multicentricity of lesions, kind and severity of symptoms, type of applied treatment modality and histopathological features of the excised tumours were additionally recorded. A meta-analysis for estimating the pooled recurrence rate after surgical excision was also conducted. Statistical significance was assumed for p ≤0.05.
We found 21 studies with histological confirmation of GCTTS. However, only 10 studies including 605 patients were reviewed according to selection criteria (average follow-up 36.7 to 79 months). The male-to-female ratio was 1:1.47 (p < 0.005) and the mean age ranged from 32 to 51 years. Pain or sensory disturbances reported only in 15.7% and 4.57% of cases, respectively. A definite history of trauma recorded in 5% of lesions. The most frequent tumour location was the index finger (29.7%). In total, 14.8% of patients had tumour recurrence. Type I tumours (single lesions) were more frequently detected (78.7%) than type II tumours (two or more distinct tumours that were not joined together) (21.3%) but the latter were associated with a higher recurrence rate (p < 0.001). Study design also affected the possibility of recurrence as it was lower in prospective studies compared to retrospective studies (p = 0.003). Even though bone erosion was detected in 28.39%, recurrence was not more common in this group. In addition, recurrence was not significantly associated with a specific finger or phalanx.
Intrinsic biology of the tumour seems to play a more fundamental role in recurrence than tumour location or local invasiveness. More prospective well-designed studies including a large number of cases are necessary to identify tumours prone to recurrence and determine the proper treatment protocol for each individual patient.
PMCID: PMC3153624  PMID: 22942846
Giant cell tumour; Tendon sheath; Digits; Hand
5.  Giant cell tumor of the anterior rib masquerading as a breast mass: a case report and review of current literature 
Cases Journal  2010;3:51.
Giant cell tumor (GCT) is an aggressive, but usually benign bone neoplasm most commonly arising in the metaphysis/epiphyses of long bones. While they are categorized as benign tumors, they can be locally aggressive and clinically have metastatic potential. The most common locations of this tumor include the distal femur, proximal tibia, and distal radius. We report a GCT arising in an atypical location and mimicking a breast mass.
Case Presentation
This case was diagnosed at a large cancer center in Florida. Pertinent clinical findings were obtained from chart review and inter-departmental consultation. Radiologically, the initial impression included a deep-seated breast cancer with local chest wall invasion. Further evaluation revealed the mass to be an expansile rib lesion with extraosseous soft tissue invasion. Histological examination of the biopsy specimen showed bland multi-nucleated giant cells and mononuclear cells whose nuclei were morphologically similar. No necrosis, pleomorphism or mitotic activity was identified. No chondroid or osseous elements were present.
The histological features of bland mononuclear and multinucleated giant cells along with the lack of any additional mesenchymal elements led to the diagnosis of giant cell tumor. Resection of tumor was performed. The patient is disease free as of the last follow-up visit. This case is important as it shows where the physician must keep this diagnosis in mind whenever a deeply located breast mast is present.
PMCID: PMC2825505  PMID: 20205847
6.  Giant cell tumor-like lesion of the urinary bladder: a report of two cases and literature review; giant cell tumor or undifferentiated carcinoma? 
Diagnostic Pathology  2009;4:48.
Giant cell tumor, excluding its prototype in bone, is usually a benign but local aggressive neoplasm originating from tendon sheath or soft tissue. Malignant behavior is uncommon. Visceral organ involvement including urinary bladder is rare. Giant cell tumors in visceral organs usually accompany epithelial tumors and the clinical behavior of giant cell tumor in urinary bladder is similar to its bone counterpart. Here, we report two cases of giant cell tumor located in urinary bladder in comparison with nine reported cases in the English literature. Concurrent noninvasive urothelial carcinoma was also described in all these previous reports and only one patient with follow-up died of disease. One of the two cases we present had no concurrent urothelial tumor at the time of diagnosis but had a history of a low grade noninvasive urothelial carcinoma with three recurrences. The histology of these two cases was similar to the giant cell tumor of bone and composed of oval to spindle mononuclear cells with evenly spaced osteoclast-like giant cells. Immunohistochemically, the giant cells showed staining with osteoclastic markers including CD68, TRAP, and LCA. Immunohistochemical expression of vimentin, CD68, LCA, and smooth muscle actin in mononuclear cells supported a mesenchymal origin with histiocytic lineage. The histologic and immunohistochemical properties in our cases as well as their clinical courses were consistent with a giant cell tumor. Consequently, tumors in urinary bladder showing features of giant cell tumor of bone may also be considered and termed "giant cell tumor".
PMCID: PMC2811699  PMID: 20043822
7.  P32 - A Case of Multicentric Giant Cell Tumours with 25-Year Follow Up 
Giant cell tumour of bone (GCT) is a relatively rare benign bone tumour more frequent in young people (20–40 years). Histologically, two cell types are represented, stromal cells of osteoblastic origin and a distinctive osteoclast-like population probably of monocytic origin. GCTs can be aggressive and they recur locally in up to 50% of cases; up to 5% of GCTs metastasise to the lungs and spontaneous transformation to a high-grade malignancy occurs in 1–3% of patients. The aetiology of GCT is not known, and no risk factors have been recognised, although familial clustering of both Paget’s disease and GCT has been reported.
GCTs account for approximately 3–5% of primary bone tumours. GCT is rarely multicentric and usually occurs at the epiphyses of long bones, but may also affect other bones.
There are few randomised, prospective clinical trials available to guide clinical management of GCT. Recent developments have led to evaluation of newer therapeutic agents, including biphosphonates and denosumab, with encouraging results. We report the case of a 66-year-old woman affected by GCT. In 1985 the patient, then 41 years old, presented a cystic lesion on her left tibia, which was removed surgically. This lesion relapsed two years later. Therefore the patient was hospitalised and received a diagnosis of “multicentric giant cell bone lesions” (limb-girdle, sternum, mandible, ribs), confirmed by histological examination. These lesions showed hyperactivity on bone scintigraphy. Plain radiographs demonstrated destructive lytic lesions. Blood and urinary examinations showed markedly elevated levels of bone alkaline phosphatase and urine pyridinoline and there was persistent bone pain. In 1993 normocalcaemic primary hyperparathyroidism was diagnosed and an adenoma was removed, with no relapse of the disease. Subsequently the patient started clodronate therapy, i.v., followed by alendronate-neridronate per os and clodronate i.m. for about nine years. Biphosphonate therapy caused a modest and transient decrease in bone indexes. Initial bone lesions were unchanged on computed tomography 25 years after diagnosis, but new bone lesions had appeared. MEN1 gene and CasR analyses were negative.
This is a rare case of a patient affected by multicentric giant cell tumours with a 25-year follow up. A slow progression of the lesion is documented, as well as the absence of significant effect of biphosphonate therapy.
PMCID: PMC3213768
8.  Central giant cell granuloma mimicking an adenomatoid odontogenic tumor 
Contemporary Clinical Dentistry  2011;2(3):249-252.
Central giant cell granulomas are non-neoplastic lesions of unknown etiology. They affect females more than males with the mandibular anterior region being the most common site of occurrence. Clinically central giant cell granulomas present as asymptomatic, expansile swellings causing deviation of associated teeth. Radiologically they usually presents as multilocular lesions causing expansion or perforation of cortical bone. Central giant cell granulomas are usually confused as other lesions both clinically and radiologically, and a definitive diagnosis can be made only histologically. We report here a rare case of central giant cell granuloma in association with congenitally missing tooth which was misdiagnosed to be an adenomatoid odontogenic tumor both clinically and radiologically. This case report also highlights yet another unique presentation of central giant cell granulomas that is in association with a congenitally missing maxillary lateral incisor.
PMCID: PMC3214539  PMID: 22090775
Adenomatoid odontogenic tumor; central giant cell granuloma
9.  Epidermal multinucleated giant cells are not always a histopathologic clue to a herpes virus infection: multinucleated epithelial giant cells in the epidermis of lesional skin biopsies from patients with acantholytic dermatoses can histologically mimic a herpes virus infection 
Multinucleated giant cells in the epidermis can either be epithelial or histiocytic. Epithelial multinucleated giant cells are most often associated with herpes virus infections.
To review the histologic differential diagnosis of conditions with epithelial and histiocytic multinucleated giant cells—since multinucleated giant cells in the epidermis are not always pathognomonic of a cutaneous herpes virus infection—and to summarize dermatoses in which herpes virus infection has been observed to coexist.
Two individuals with acantholytic dermatoses whose initial lesional skin biopsies showed multinucleated epithelial giant cells suggestive of a herpes virus infection are reported. Using the PubMed database, an extensive literature search was performed on multinucleated giant cell (and epidermis, epithelial, and histiocytic) and herpes virus infection. Relevant papers were reviewed to discover the skin conditions with either multinucleated giant cells in the epidermis or coincident cutaneous herpes virus infection.
Initial skin biopsies from patients with either pemphigus vulgaris or transient acantholytic dermatosis mimicked herpes virus infection; however, laboratory studies and repeat biopsies established the correct diagnosis of their acantholytic dermatosis. Hence, epidermal multinucleated giant cells are not always a histopathologic clue to a herpes virus infection. Indeed, epithelial multinucleated giant cells in the epidermis can be observed not only in the presence of infection (herpes virus), but also acantholytic dermatoses and tumors (trichoepithelioma and pleomorphic basal cell carcinoma). Histiocytic multinucleated giant cells in the epidermis can be observed in patients with either giant cell lichenoid dermatitis or lichen nitidus of the palms.
Epithelial and histiocytic multinucleated giant cell can occur in the epidermis. Keratinocyte-derived multinucleated giant cells are most commonly associated with herpes virus infection; yet, they can also be observed in patients with skin tumors or acantholytic dermatoses. Cutaneous herpes simplex virus infection can coexist in association with other conditions such as acantholytic dermatoses, benign skin tumors, bullous disorders, hematologic malignancies, inflammatory dermatoses, and physical therapies. However, when a herpes virus infection is suspected based upon the discovery of epithelial multinucleated giant cells in the epidermis, but either the clinic presentation or lack of response to viral therapy or absence of confirmatory laboratory studies does not support the diagnosis of a viral infection, the possibility of a primary acantholytic dermatosis should be considered and additional lesional skin biopsies performed. Also, because hematoxylin and eosin staining is not the golden standard for confirmation of autoimmune bullous dermatoses, skin biopsies for direct immunofluorescence should be performed when a primary bullous dermatosis is suspected since the histopathology observed on hematoxylin and eosin stained sections can be misleading.
PMCID: PMC4230253  PMID: 25396080
acantholytic; cell; dermatoses; dermatosis; disease; epidermis; epithelial; giant; Grover; herpes; infection; multinucleated; pemphigus; transient; virus; vulgaris
10.  Undifferentiated giant cell type carcinoma of the gallbladder with sarcomatoid dedifferentiation: a case report and review of the literature 
Undifferentiated gallbladder carcinoma is a rare entity. Among unusual types of undifferentiated gallbladder carcinoma, giant cell type carcinoma is infrequent and, moreover, very few cases of such neoplasms with osteoclast-like giant cells have been documented. We report a case of undifferentiated gallbladder carcinoma presenting an unusual immunophenotype that was shown to be of giant cell type with sarcomatoid dedifferentiation infiltrated by osteoclast-like multinucleated cells.
Case presentation
An 84-year-old Greek man presented with right upper quadrant pain, high fever, rigors, anorexia and weight loss during the past month. Clinical examination revealed tenderness in the right upper abdominal quadrant and a palpable gallbladder. Blood tests showed elevated white blood-cell count and transaminases. Abdominal ultrasound and computed tomography demonstrated a markedly distended gallbladder, measuring 16 cm x 8 cm, with oedema and pericholecystic fluid, consistent with gallbladder empyema. After an open cholecystectomy and an uneventful recovery, the patient was discharged on the 4th postoperative day. On cut surface, a 2cm solid mass was identified, obstructing the lumen in the neck of the gallbladder. Histopathology and immunohistochemistry offered the diagnosis of an undifferentiated, giant cell type carcinoma of the gallbladder with sarcomatoid dedifferentiation infiltrated with osteoclast-like giant cells.
Undifferentiated, giant cell type carcinoma of the gallbladder with sarcomatoid dedifferentiation infiltrated with osteoclast-like giant cells is a very infrequent neoplasm. Controversy exists over its nature, as related knowledge remains incomplete. Thorough histopathological and immunohistochemical evaluation is imperative for diagnosis. Due to their rarity, the biological behaviour and prognosis of these tumours remain unclear.
PMCID: PMC2726484  PMID: 19830109
11.  Computer assisted histomorphologic comparision and the expression of AgNORs in the central and peripheral giant cell lesions of the oral cavity and giant cell tumor of the long bone 
Computer-assisted image analysis was attempted to ascertain, if any of the previously described histologic features along with argyrophilic nucleolar organizer regions (AgNORs) could be used to determine the aggressiveness of the central giant cell granuloma of the jaws (CGCG), peripheral giant cell granuloma of the oral cavity (PGCG) and giant cell tumor of the long bones (GCT).
Study Design:
The study consisted of 20 cases of CGCG, 20 cases of PGCG and 5 cases of GCT. The histological features included were number of giant cells, number of nuclei in each giant cell, number of blood vessels, fractional surface area (FSA) and relative size index (RSI) of giant cells. The histologic parameters were measured using Motic image plus analyzer and AgNORs were evaluated using silver stain.
The statistical analysis showed significant differences among various histological parameters between CGCG, PGCG and GCT. A statistically significant difference was noted for the mean number of nuclei, FSA and RSI when GCT was compared with CGCG and PGCG. FSA of histologically aggressive central giant cell granuloma (HA-CGCG) was more compared to histologically non-aggressive central giant cell granuloma (HNA-CGCG). No statistical correlation was observed for AgNORs of multinucleated giant cells and mononuclear cells among CGCG, PGCG and GCT.
Based on the present study findings, CGCG and GCT are distinct and separate entities and not a continuum of a single disease process. Histological parameters alone have a little implication on predicting clinical behavior of CGCG. AgNORs alone as a proliferative marker has a limited value in assessing the proliferation potential of giant cell lesions.
PMCID: PMC4211239  PMID: 25364180
Argyrophilic nucleolar organizer regions; central giant cell granuloma; giant cell tumor; peripheral giant cell granuloma
12.  Giant cell ependymoma of the cervical spinal cord: case report and review of the literature 
European Spine Journal  2008;18(Suppl 2):186-190.
Ependymomas account for 2–6% of all central nervous system neoplasms. They develop from the ependymal cells that line the ventricular cavities of the brain and the central canal of the spinal cord, as well as from ependymal clusters in the filum terminale. Giant cell ependymoma (GCE) is a rare subtype, with few cases reported, mostly in the brain. We describe the case of a cervical spinal cord ependymoma with pleomorphic giant cells and focal calcifications occurring in a 25-year-old woman. Magnetic resonance imaging revealed a large multicystic and partially enhancing intramedullary tumour extending from C2 to C5. Intraoperative analysis of frozen section tissue fragments suggested a malignant tumour; however, an obvious cleavage plane was present around most of the mass, and a macroscopically complete tumour removal could be achieved. Subsequently, paraffin sections and immunohistochemical investigations revealed unequivocal evidence of a GCE with focal calcifications. This case, the second giant-cell ependymoma to be described in the spinal cord and the first with focal calcifications, highlights the features of GCE and the discrepancy between the worrisome histological appearance, the surgical findings and the clinical relatively good prognosis.
PMCID: PMC2899556  PMID: 18820954
Giant cell ependymoma; Calcifications; Ependymoma; Spinal cord; Tumour
13.  Visceral Leishmaniasis with Associated Common, Uncommon, and Atypical Morphological Features on Bone Marrow Aspirate Cytology in Nonendemic Region 
Journal of Tropical Medicine  2013;2013:861032.
Objectives. The present study was conducted to categorise the morphological features on bone marrow aspirate cytology into common, uncommon, and atypical features in a nonendemic region which would be helpful in clinching an early and correct diagnosis especially in clinically unsuspected cases. Methods. The morphological features on bone marrow were categorized into common, uncommon, and atypical in cases of leishmaniasis from non endemic region. Results. Out of total 27 cases, 77.7% were residents of places at the height of 500 m or above and fever was the most common presentation followed by hepatosplenomegaly. Plasmacytosis, hemophagocytosis were the common cytological features while dysmyelopoiesis, presence of leishmania bodies in nonhistiocytic cells, and granuloma with necrosis were uncommon features. Aggregates of LD bodies in form of ring, floret, or strap shapes along with giant cells constitute the atypical morphological features. Conclusion. The knowledge of common, uncommon, and atypical features on bone marrow aspirate cytology is helpful in clinching an early and correct diagnosis of leishmaniasis especially in non endemic areas where clinical suspicion is low. These features will guide the pathologist for vigilant search of LD bodies in the marrow for definite diagnosis and thus will also be helpful in preventing unnecessary workups.
PMCID: PMC3782059  PMID: 24089618
14.  Fine Needle Aspiration Cytology: A Useful Technique for Diagnosis of Invasive Fungal Rhinosinusitis 
Head and Neck Pathology  2013;7(3):236-240.
Mycotic infections are on the rise globally. Patients with invasive fungal infection of the paranasal sinuses often present with destructive mass lesions and mimic malignancy clinically and radiologically. To assess the utility of Fine needle aspiration cytology for early diagnosis of invasive fungal rhinosinusitis. Fine needle aspiration cytology was performed from the maxillary/ethmoid sinus in patients with a destructive mass lesion in the maxilla. Differential diagnoses were malignancy and fungal rhinosinusitis. In eight cases fungi were detected on initial examination whereas in a single case that was initially reported as giant cell lesion, hyphae could be identified within giant cells, on review. Smears showed inflammatory cells with variable numbers of eosinophils with neutrophils and histiocytes. Foreign body giant cells were seen in all cases. The fungi conformed to morphology of aspergillus in seven cases (77.78 %); in two cases (22.22 %), typing could not be done. Periodic acid Schiff and Grocott stains highlighted the fungi in all the cases. Fine needle aspiration is a simple technique that can be useful for diagnosis of fungal rhinosinusitis and to exclude malignancy. Search for fungus may be more aggressive in smears with many foreign body giant cells and inflammatory cells and in cases with a high clinical suspicion. Differentiation between aspergillus and mucor can be made with help of special stains. Aspergillus is the commonest agent isolated. Preoperative cytological diagnosis obviates the need for biopsy, saves time and helps to plan proper treatment.
PMCID: PMC3738751  PMID: 23475692
Fine needle aspiration (FNA); Cytology; Invasive fungal rhinosinusitis; Aspergillosis; Mycotic rhinosinusitis; Paranasal sinus mycoses
15.  Differential considerations of skin tumours with florid vascularisation: report of a solitary giant vascular eccrine spiradenoma 
BMJ Case Reports  2011;2011:bcr0520114187.
The authors report the case of an 81-year-old male who presented with a 3-year-history of a bluish, nodular tumour located on the extensor side of his right forearm. Subjective symptoms included tenderness upon palpation and spontaneous haemorrhage. In order to exclude malignant neoplasms, for example, nodular melanoma, metastatic melanoma or angiosarcoma, the tumour was surgically removed and tissue submitted for microscopic examination. Histologically, the authors diagnosed this as giant vascular eccrine spiradenoma, a rare variant of eccrine spiradenoma, which can easily be mistaken for angiomatous lesions due to the haemorrhagic features and florid vascularisation. It is our aim to help clarify the diagnosis and differentiate giant vascular eccrine spiradenoma from other painful cutaneous tumours exhibiting a high degree of vascularisation, for example, angiosarcoma or venous thrombosis, as this case represents one of only seven found in published literature.
PMCID: PMC3143330  PMID: 22689604
16.  Chronic periaortitis (retroperitoneal fibrosis) concurrent with giant cell arteritis: a case report 
Giant cell arteritis is the most common form of large-vessel vasculitides. However, it is probable that extracranial involvement is underdiagnosed in patients with classical giant cell arteritis. In the recent literature most cases of giant cell arteritis have been described in conjunction with aortic aneurysms or dissections. Nonetheless the coexistence of giant cell arteritis and retroperitoneal fibrosis is extremely rare. Here, we describe a case of giant cell arteritis at a very early clinical stage, in a woman with coexistence of retroperitoneal fibrosis.
Case presentation
We report a case of giant cell arteritis at a very early clinical stage, in a 47-year-old Greek woman with coexistence of retroperitoneal fibrosis who was admitted to our hospital with a history of high-grade fever and mild right periumbilical abdominal pain for the past 30 days. In the context of fever of unknown origin, an abdomen computed tomography was ordered. A temporal artery biopsy was also performed because during hospitalization she complained of a headache. Examination of eosin and hematoxylin slides from biopsy specimens of her temporal artery, showed lesions consisting of predominantly lymphocytes, few plasma cells and occasional polymorphonuclear leucocytes. In addition no giant cells were detected in examining biopsies at multiple levels. This was consistent with giant cell arteritis according to the American college of Rheumatology criteria. An abdomen computed tomography revealed the presence of a retroperitoneal soft-tissue mass located anteriorly to the upper infrarenal aorta at the site of the scintigraphic uptake. The computed tomography and magnetic resonance imaging characteristics of the mass were consistent with retroperitoneal fibrosis, and its morphology suggestive of benignity. Our patient started oral prednisolone and was afebrile from day one.
In our experience this is the first case of retroperitoneal fibrosis due to giant cell arteritis occurring at the same time. Involvement of the aorta (aortitis) and its branches has been also observed in a subset of patients with giant cell arteritis. In addition, giant cell arteritis has been associated with a markedly increased risk of aortic aneurysm particularly thoracic aortic aneurysm.
PMCID: PMC4070639  PMID: 24885445
Giant cell arteritis; Periaortitis; Retroperitoneal fibrosis
17.  Osteoclast-type giant cell tumour of the pancreas. 
Journal of Clinical Pathology  1983;36(10):1165-1170.
A case of osteoclast-type giant cell tumour of the pancreas is described and the features of eight other previously reported patients are reviewed. Characteristically, these neoplasms are large at presentation and show focal haemorrhage and necrosis, but seem slow to give rise to metastases. Histological examination reveals numerous osteoclast-like giant cells set in a sarcomatous stroma, the appearances being similar to those seen in giant cell tumours of bone. They are distinct from pleomorphic giant cell carcinomas of the pancreas and may have a slightly better prognosis after resection than ordinary adenocarcinomas. The histogenesis of these rare tumours is unknown.
PMCID: PMC498495  PMID: 6619312
18.  Giant Keratoacanthoma of the Upper Extremity Treated with Mohs Micrographic Surgery 
Keratoacanthomas are fast-growing, solitary, cutaneous neoplasms that usually show spontaneous regression. The development of giant variants and aggressive behavior have been described. Clinically, a keratoacanthoma larger than 20 to 30mm is classified as a giant keratoacanthoma. A major challenge in dealing with these neoplasms is the difficulty of clinically and histologically differentiating them from squamous cell carcinoma. The authors report a practical approach using Mohs micrographic surgery for evaluation of large tumors. With this method, the lateral margins are evaluated and cleared prior to excision of the bulk of the tumor. The authors also describe alternative therapies for giant keratoacanthomas and present a case of a 61-year-old woman with a rapidly growing tumor on her left arm. Skin biopsy was consistent with a well-differentiated squamous cell carcinoma with focal features of a keratoacanthoma. The patient underwent Mohs micrographic surgery using the described approach, and no recurrence has been noted in four years. Surgical excision remains the treatment of choice for giant keratoacanthomas. Mohs micrographic surgery is a logical treatment option for giant keratoacanthomas. This case illustrates a useful approach that may prove valuable when treating large specimens during Mohs micrographic surgery.
PMCID: PMC2923962  PMID: 20729950
19.  Management of the giant-cell tumours of the distal radius. 
BACKGROUND: Giant-cell tumour of the distal radius is a rare neoplasm that affects the peri-articular metaphysial region of the bone. Curettage alone or with bone grafting has been reported to be associated with high incidence of local recurrence in these tumours. In the present series, we report the results of curettage only as the treatment for primary giant-cell tumour of the distal radius carried out at a single centre. PATIENTS AND RESULTS: A total of 287 patients with giant-cell tumour have been referred to us for treatment over the last 28 years; 24 of these were found to have lesion in the distal radius. One patient underwent endoprosthetic replacement of the distal radius. The remaining 23 patients underwent curettage of the primary neoplasm. Four out of the 23 (17%) patients developed local recurrence of disease, The mean time to local recurrence was 17 months (range, 9-27 months). Complications such as collapse of the articular cartilage are more common in patients with an extensive soft tissue component of the tumour. CONCLUSIONS: Curettage alone is adequate treatment for the majority of patients with giant-cell tumours of the distal radius but some form of stabilisation may be required in the presence of extensive bone destruction.
PMCID: PMC1964006  PMID: 15005940
20.  Use of a Distal Radius Endoprosthesis Following Resection of a Bone Tumour: A Case Report 
Sarcoma  2010;2009:938295.
Limited literature is available on the reconstruction of the distal radius using prosthetic replacement following resection of a bone tumour. We present the first reported case, in the English literature, of the use of an entirely metal endoprosthesis for the reconstruction of the distal radius. This case involves a 66-year-old male who was treated for giant cell tumour of the distal radius with surgical excision of the lesion and replacement of the defect using a predominantly titanium endoprosthesis. He was followed-up for 56 months following surgery and had a good functional outcome with no associated pain or complications. We propose that the use of a primarily titanium endoprosthesis for the reconstruction of a bone defect of the distal radius is a suitable alternative, providing good function of the forearm with satisfactory range of movement at the wrist and adequate pain relief.
PMCID: PMC2831197  PMID: 20204177
21.  Giant cell tumour of tendon sheath (localised nodular tenosynovitis): clinicopathological features of 71 cases 
Journal of Clinical Pathology  2001;54(5):404-407.
Aims/Background—Giant cell tumour of the tendon sheath (GCTTS) is regarded as the most common neoplasm of the hand that can recur after excision. The objective of this study was to review a series of cases in our department and to determine any clinical or pathological features that might predict the likelihood of recurrence.
Methods—Clinical data, obtained from pathology request forms and in patient notes, along with the gross and microscopic appearances of 71 cases of GCTTS were evaluated.
Results—Clinical features and pathological features identified were similar to those of previous studies. In comparison with previous studies a higher mitotic count (range, 1–21 mitoses/10 high power fields (HPF); mean, 5/10 HPF) was noted in all cases, irrespective of recurrence and numerous apoptotic bodies (up to 30/10 HPF), mainly formed from osteoclast-like giant cells, were present.
Conclusions—GCTTS is a relatively rare soft tissue tumour of uncertain histiogenesis. Mitotic and apoptotic figures are a common feature and do not indicate clinical behaviour. Complete local excision is the treatment of choice.
Key Words: giant cell tumour tendon sheath • apoptosis • osteoclasts
PMCID: PMC1731411  PMID: 11328844
22.  Fine needle aspiration cytology of bone tumours- the experience from the National Orthopaedic and Lagos University Teaching Hospitals, Lagos, Nigeria 
CytoJournal  2006;3:16.
Due to difficulty in confirming clinical suspicions of malignancy in patients presenting with bone tumours, the cost of surgical biopsies where hospital charges are borne almost entirely by patients, competition with bone setters and healing homes with high rate of loss to follow up; we set out to find if sufficient material could be obtained to arrive at reliable tissue diagnosis in patients with clinical and radiological evidence of bone tumours in our hospitals.
After initial clinical and plain radiographic examinations, patients were sent for fine needle aspirations. Aspirations were carried out with size 23G needles of varying lengths with 10 ml syringes in a syringe holder (CAMECO, Sebre Medical, Vellinge, Sweden). The aspirates were air dried, stained by the MGG method and examined microscopically. Histology was performed on patients who had subsequent surgical biopsy. These were then correlated with the cytology reports.
Out of 96 patients evaluated, [57 males, 39 females, Mean age 31.52 years, Age Range 4–76 years,] material sufficient for diagnosis was obtained in 90 patients. Cytological diagnosis of benign lesions was made in 40 patients and malignant in 47. Of these, 27 were metastases, osteogenic sarcoma 16, giant cell tumour 19, infection 11. Histology was obtained in 41 patients. Correct diagnosis of benignity was made in 17 out of 18 cases, malignancy in 21 out of 22 cases. One non-diagnostic case was malignant. The accuracy of specific cytological diagnosis was 36/41 (87.8%) and incorrect in 5/41 (12.2%).
We conclude that FNAC can be useful in the pre-operative assessment of bone tumours especially where other diagnostic modalities are unavailable.
PMCID: PMC1526751  PMID: 16776844
23.  Histologically verified lung metastases in benign giant cell tumours—14 cases from a single institution 
International Orthopaedics  2006;30(6):499-504.
From 1975 to 1997, 649 cases of benign giant cell tumours of the bone were treated at the Istituto Rizzoli. Fourteen patients (2.1%) experienced lung metastases after a mean of 35.2 months. The time interval between the diagnosis and the appearance of the lung metastases ranged from 3 months to 11.9 years. Metastasectomy was performed in all patients. Histologically, the metastases were identical to the primary bone lesions. Two patients with unresectable multiple metastases received additional chemotherapy. After a follow-up of 70 months (range: 8.2 to 185 months), all patients are alive. Ten patients showed no evidence of disease, one of these after a second resection of metastases, and four patients presented stable disease with multiple lung metastases. Local recurrence of the bone lesion occurred in seven patients before or simultaneously to the metastases. In contrast to previous reports, we could not detect a predominance of the distal radius, but all of the patients had a stage III tumour according to the Enneking criteria of benign lesions. We conclude that even metastatic benign giant cell tumours have an excellent prognosis after adequate resection. No prognostic factors despite high-grade lesions were detectable.
PMCID: PMC3172731  PMID: 16909252
24.  Fibrous Dysplasia and Central Giant Cell Granuloma: A Report of Hybrid Lesion with its Review and Hypotheticated Pathogenesis 
Benign fibro—osseous lesions (BFOLS) of the jaws are a wide array of lesions that actually represent distinct phases of a single benign morphological process. These lesions share certain histopathological features which are in common with giant cell containing lesions, which include central giant cell granulomas (CGCGs). The association of BFOLS and CGCG has to be critically evaluated, pertaining to their clinical, radiologic and histologic features. Many pathologists diagnose these types of lesions, considering only one of the prominent features. Eventually, surgeons end up treating these lesions inadequately. This ambiguity may be because of very small number of cases have been reported in the literature, with uncertain clinical, radiologic and histologic features. We are reporting a case of fibrous dysplasia (FD) which was associated with a central giant cell granuloma (CGCG) and discussing the hypothetical pathogenesis of giant cells.
PMCID: PMC3681081  PMID: 23814754
Fibrous dysplasia; Granuloma giant cell; Hybrid; Dimorphic; Stromal cells; Osteoclasts
25.  Fibro-osseous lesions vs. central giant cell granuloma: A hybrid lesion 
Fibro-osseous lesions of the jaws can have certain histologic features in common with central giant cell granuloma (CGCG) including the presence of multinucleated giant cells. The clinical, radiologic and histologic features of these lesions should be carefully evaluated to distinguish between these conditions. Fibro-osseous lesions of the jaws are a heterogenous group of lesions characterized by the replacement of normal bone by fibrovascular tissue containing newly formed mineralized material. Central giant cell lesions are defined as an intraosseus lesion consisting of cellular fibrous tissue containing multiple foci of hemorrhage and aggregation of multinucleated giant cells. These lesions may sometimes lead to a confusion in their diagnosis as many pathologists report them taking into consideration one of the prominent histopathologic feature. These confusions may be because of the small number of cases reported in the literature with uncertain clinical, radiographic and histopathologic features of these lesions. So even surgeons may end up treating these lesions inadequately or patients may need to undergo multiple surgeries. We report such a case of Juvenile ossifying fibroma associated with CGCG and discuss the clinical, imaging, histologic, and treatment aspects of this hybrid lesion.
PMCID: PMC3591046  PMID: 23483611
Central giant cell granuloma; fibro-osseous lesions; hybrid lesion

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