Skeletal Radiol (1992) 21:482-488

Skeletal Radiology

Case report 757 Rafik M. Hanna, M.D. 1' *, Michael Kyriakos, M.D. 2, and Stephen F. Quinn, M.D. 3 Departments of 1 Pathology and 3 Radiology, Oregon Health Services University and Good Samaritan Hospital, Portland, Oregon, U S A 2 Lauren V. Ackerman Division of Surgical Pathology, Washington University School of Medicine, St. Louis, Missouri, USA

Imaging studies

Fig. 1. Coned-down plain roentgenogram of lower right lateral chest shows a destructive rib lesion. A soft-tissue mass containing calcifications is present (arrows)

9 1992 International Skeletal Society

Fig. 2. A radionuclide bone scan shows intense uptake in the region of the lesion Fig. 3A, B. Two views of a contrast-enhanced CT scan show a large, expanding mass originating from the anterolateral as-

pect of the rib. Most of the mass is of softtissue density, but linear calcifications are present. An incomplete rim of bone surrounds the mass which extends medially to compress the liver and lateralIy into the soft tissues of the chest wall

R.M. Hanna et al. : Case report 757 Clinical information

A 29-year-old white male farmer was admitted to the Good Samaritan Hospital, Portland, Oregon in September 1989 because of a painful, right-sided mass of the chest wall. Approximately 18 months previously, he had developed pain in the right side of his chest while pitching hay. During the ensuing months, he had recurrent episodes of this pain associated with the development of a mass. On admission, the physical ex* Current address: Department of Pathology, University of Iowa Hospitals and Clinics, 5244 RCP, Iowa City, IA 52242, USA Correspondence to. Dr. Rafik M. Hanna at current address

483 amination was normal except for a tender, hard, fixed mass in the right anterolateral chest wall that measured approximately 15 cm and extended beyond the right costal margin to overlie the liver. Results of routine laboratory studies were normal, including values for serum calcium, phosphorus, and alkaline phosphatase. A plain chest roentgenogram showed destruction of the lateral aspect of the right ninth rib with evidence of a large soft-tissue mass containing calcific densities (Fig. 1). A technetium-99m methylene diphosphonate bone scan showed intense uptake of radionuclide by the lesion (Fig. 2). A contrast-enhanced corn-

puted tomography (CT) scan showed an 8.0 x 6.0 cm heterogeneous mass originating from the anterolateral aspect of the rib. Although most of the lesion was of soft-tissue density, it did contain several linear calcified densities. Around its periphery was an irregular and incomplete peripheral calcific shell. The mass was dumbell-shaped with medial extension into the abdominal cavity, causing extrinsic compression of the liver, and lateral projection into the soft tissue of the chest wall (Fig. 3). The radiological differential diagnoses included metastatic carcinoma, osteosarcoma, chondrosarcoma, hemangioendothelioma, plasmacytoma, and aneurysmal bone cyst.

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Diagnosis: Giant cell tumor of rib Tissue from an open biopsy of the t u m o r was initially diagnosed as a malignant giant cell t u m o r ( M G C T ) based on the lesion's large size, apparent soft-tissue extension, and stromal cell mitotic activity. However, the material sent to one of us in consultation was interpreted as a conventional giant cell tumor (GCT) without evidence of malignancy. However, because of the lesion's aggressive radiological appearance, the clinical staff believed that the tumor was malignant, and over the next 2 months the patient was treated with systemic doxorubicin (90 mg total dose) and 4000 rads of external radiation therapy. On N o v e m b e r 30, 1989, the t u m o r and the eighth, ninth and tenth ribs were excised in toto; the t u m o r was found adherent to, but not invading, the liver and was removed from its surface by adhesiotomy. On gross examination, the t u m o r arose in and essentially obilerated the ninth rib without involving the adjacent ribs. It was enclosed by a thick capsule that was intact except on its medial margin where there were several 0.1 x 0.1 specks of brownish tum o r tissue. On section, the t u m o r was soft, with myxoid-like regions and extensive areas of necrosis, and varied f r o m bright yellow to bright red. The more viable-appearing areas were beefy-red with rare yellow bone spicules. Firm bone was present at its periphery. Histological examination of the biopsy tissue showed a diffuse proliferation of multinucleated, osteoclasttype giant cells and oval to spindleshaped stromal cells without significant cell atypia. The nuclei of the giant cells and the stromal cells appeared similar (Figs. 4, 5). Mitotic activity was easily found in the stromal cells, but not in the giant cells; atypical mitoses were not seen. Fibrotic areas containing hemosiderin were also present. The resection material showed an essentially similar histological pattern; however, widespread areas of necrosis and hemorrhage were now present as well as more extensive fibrotic zones containing numerous f o a m y histiocytes. Degenerate osteoclast-type giant

R.M. Hanna et al. : Case report 757

Pathological studies

Fig. 4. Section of rib tumor shows diffuse proliferation of benign-appearing multinucleated giant cells and intervening stromal cells. H & E, x 300 Fig. 5. Higher magnification shows giant cells and oval to spindle-shaped stromal cells. The stromal cell nuclei are similar to those of the giant cells. Although mitotic activity is frequent in the stromal cells (arrows), there is no evidence of cell atypia. H & E, x 600

R.M. Hanna et al. : Case report 757 cells, with small, round, and necrotic nuclei, were found scattered among the viable-appearing osteoclast-type giant cells. The tumor was highly vascular, with some areas having small, gaping, aneurysmal bone cystlike spaces that contained free-floating osteoclast-type giant cells. The tumor had extensively destroyed the rib and extended, in a pushing fashion, into the adjacent soft tissue with thick periosteal fibrosis at its advancing margin (Fig. 6). This fibrotic " c a p s u l e " contained evidence of old hemorrhage, and in some areas the fibroblasts showed nuclear atypia consistent with radiation effect. Remnants of the cortex, as well as possible neocortex, were present and fenestrated by tumor (Fig. 6). Fracture callus, with periosteal new bone formation, was also present. Foci of new bone formation were found at the growing margin of the tumor as well as within its more central portions. No malignant-appearing bone, cartilage, or spindle cells were discovered. Cytochemical stains for acid phosphatase, done on fresh frozen tumor tissue, showed intense acid phosphatase activity in the cytoplasm of the giant cells, with focal, weak, stromal cell staining. Fresh tumor tissue processed for flow cytometry showed a low proliferative activity (S-phase fraction 8%), with a diploid pattern; there was no evidence of aneuploidy. Following recovery from his operation, the patient was alive and well and without evidence of recurrence as of June 14, 1991.

485

Fig. 6. Portion of resected rib shows the tumor penetrating the cortical bone in a pushing fashion. A thickened periosteum is present adjacent to the tumor. H & E, • 90

nated in the ribs [3, 6, 10, 15, 23, 27, 35, 38]. In a review of the literature of tumors of the thoracic wall in 1942, Sommer and Major collected 78 rib tumors, only 9 of which were G C T [37]. One of these had been reported by Peirce [29] as a "chondro-osteogenic sarcoma" arising in a G C T in a 17-year-old boy; however, from the meager microscopic description supplied, as well as the illustrations, we believe that this tumor was probably a primary osteosarcoma in which there was a proliferation of osteo-

clast-type giant cells. In 1950, Buckles and Lawless reviewed the literature of G C T of the ribs and listed the same cases as did Sommer and Major and added a benign G C T of their own [2]. In 1953, Hochberg reviewed the literature on primary rib tumors, exclusive of eosinophilic granuloma [13], and among the 106 benign tumors mentioned, the only cases of G C T were those previously reported by Sommer and Major and Buckles and Lawless. Of 99 malignant tumors listed, only I was a M G C T , the case being reported by

Discussion

Approximately 80% of giant cell tumors (GCT) of bone arise at the ends of the long bones, with the distal ends of the femur, proximal ends of the tibia, and distal ends of the radius accounting for approximately twothirds of the cases; just over one-half of all cases are located in the bones around the knee joint [3, 6, 10, 15, 23, 27, 35, 38]. G C T of the rib is distinctly uncommon. In a review of 8 large series of giant cell tumors in the English medical literature, each containing over 100 cases, totalling 2128 cases (Table 1), only 12 (0.6%) origi-

Table 1. Giant cell tumor of rib" Reference

Number b

Percentage

Campanacci et al. (1987) [3] Dahlin and Unni (1986) [6] Goldenberg et al. (1970) [10] Huvos (1991) [15] McInerney and Middlemiss (1978) [23] Netherlands Tumor Registry (1973) [27] Schajowicz (1981) [35] Sung et al. (1982) [38]

1/327 3/453 0/232 4/257 2/135 0/161 2/347 0/216

0.3 0.7

12/2128

0.6

Total

1.6 1.5 0.6

a Abstracted from series containing a minimum of 100 cases of giant cell tumor b Number of giant cell tumors of rib to total number of giant cell tumors in series

486 Guglielmini and Pironti in the Italian literature [11]. Their patient was a 59-year-old woman who died within 3 months of a giant-cell-containing tumor of the third rib. The histological pattern of the lesion is not illustrated, and whether the tumor would satisfy the current criteria for a M G C T is questionable. Locher and Kaiser reported 3 cases of rib tumors in young children (aged 4.5, 13.5, and 14 years) which they believed were either GCTs or aneurysmal bone cysts [19]. From the histologic descriptions, it is difficult to determine what these lesions were, but the young ages of the patients would argue against a diagnosis of GCT. The distribution of benign tumors or tumor-like conditions of the rib, versus that of primary malignant tumors, differs somewhat in two large series in the literature in which such data are given. In a tabular summary of the Mayo Clinic experience, Dahlin and Unni list 265 malignant and 37 benign rib tumors [6]. In the malignant category, hematopoietic tumors, malignant lymphoma, and myeloma accounted for almost half the cases; among the remainder, in descending order of frequency, chondrosarcoma, Ewing's sarcoma, and osteosarcoma were the most common. The 37 benign entities listed did not include fibrous dysplasia or aneurysmal bone cyst. When these entities are included, there were 88 benign lesions - the most frequent of these, in descending order, was fibrous dysplasia, osteochondroma, aneurysmal bone cyst, and chondroma.

The Netherlands Tumor Registry lists 109 rib lesions, of which 52 were malignant and 57 benign, the latter including benign tumors and tumorlike lesions [27]. Among the malignant tumors, which did not include examples of myeloma, the most common, in oi-der of descending frequency, were chondrosarcoma, Ewing's sarcoma, and osteosarcoma; among the benign entities, fibrous dysplasia, angioma, a n d chondroma were the most frequent.. Pascuzzi et al., in a study of 126 rib tumors at the Mayo Clinic, found that although benign lesions were evenly distributed throughout the en-

R.M. Hanna et al. : Case report 757 tire rib cage, malignant rib tumors most frequently involved the anterior segments of the upper five ribs. In about 25% of their cases, the lesions arose in the first or second rib [28]. Due to the aggressive radiological appearance of our patient's tumor, with possible liver involvement, a clinical diagnosis of M G C T was entertained, and chemotherapy and radiation therapy were given preoperatively. Primary M G C T is a rare tumor [3, 5, 24, 26, 32, 33, 38], especially if strict histological criteria [6, (p. 337) 7, 15, 26, 32] for its diagnosis are adhered to so as to avoid confusion with other malignant giant-cellcontaining tumors [25]. Most socalled MGCTs develop following radiation therapy of an otherwise histologically benign GCT [3, 6, (p. 337) 14, 32, 33]. Such secondary tumors are more appropriately considered postradiation sarcomas and not MGCTs. So-called evolutionary MGCTs also exist in which a sarcoma develops at the site of a previous GCT treated only surgically [6 (p. 337), 14, 15, 22]. For a diagnosis of primary MGCT, areas of conventional GCT must be present or juxtaposed to areas of obvious sarcoma [6 (p. 337), 7, 15, 26, 32]. Using this criterion, the incidence of primary M G C T is certainly less than 10%, and probably closer to 1%-5%, of all GCTs [3, 6 (p. 337), 24, 26, 32, 33]. Meis et al. in a study of M G C T emphasized the juxtaposition of the sarcoma to the areas of benign GCT, and the abrupt change between the two without gradual transition. They believe that M G C T represents a form of "dedifferentiation" of conventional GCT [24]. However, it is not clear from a reading of the literature on M G C T whether all cases of M G C T have, or need to have, such an abrupt demarcation of the sarcomatous foci from the benign giant cell areas in order to be considered a M G C T [6 (p. 337), 25, 26]. We were unable to find an acceptable example of M G C T of the rib in the English medical literature. Radiological aggressiveness is not useful in distinguishing benign from malignant forms of GCT, as the benign forms may have cortical expansion and disruption with invasion of the soft tissue [6, 15, 21, 25, 31], fit-

ting the criteria of a radiological grade III lesion as proposed by Campanacci et al. [3]. Despite the tumor in our patient extending beyond the bone into the soft tissue, there was no histologic evidence, in either the biopsy or resection material, of sarcomatous foci. Although the flow cytometry data, which showed an absence of an aneuploid peak, argues against a high-grade sarcoma in our patient, most GCTs that have been studied, including those that developed pulmonary metastases, have been diploid. Thus, flow cytometry evaluation is not a useful method for distinguishing clinically aggressive from nonaggressive forms [17, 34, 36]. In our case, the radiological presence of a shell of bone around the tumor was a clue to its benign character despite its compression of the liver. The occurrence of intravascular giant cells, foam cells, aneurysmal bone cyst-like areas, abundant mitotic activity, ossification, and invasion of the soft tissues, as present in our case, have all been reported in conventional GCT [4, 6, 7, 10, 14, 15, 25, 33, 351. Histologically, the two lesions most easily confused with true GCT are giant cell reparative granuloma and the brown tumor of hyperparathyroidism. Both of these lesions share a similar histologic pattern which classically consists of a fibrogenic stroma containing areas of hemorrhage about which cluster multinucleated osteoclast-type giant cells that are somewhat smaller and contain fewer nuclei than those in conventional GCT. Hence, the distribution of the giant cells in these lesions is irregular and focal versus their more even distribution in true GCT, and the stroma is more fibrogenic and reactive in appearance than is that within the diagnostic areas of GCT [1, 9, 15, 25]. However, when only a small amount of biopsy tissue is available, the histological distinction between these entities may prove difficult or impossible, and clinical information is required to separate them. Giant cell reparative granuloma occurs mainly in the jaw bones and occasionally in the bones of the hands and feet [20, 30, 40] and has only rarely been reported elsewhere [8, 12, 16, 39]. We are unaware of

R.M. Hanna et al. : Case report 757 a n y cases, in the English m e d i c a l lite r a t u r e , o r i g i n a t i n g in the ribs. A l though brown tumors may occur a n y w h e r e in the skeleton, the presence o f o t h e r r a d i o l o g i c a l f e a t u r e s o f hyperparathyroidism and elevated s e r u m c a l c i u m levels help to distinguish b r o w n t u m o r f r o m c o n v e n t i o n al G C T . In o u r case, the diffuse p r o l i f e r a t i o n o f g i a n t cells, as well as o v a l to s p i n d l e - s h a p e d s t r o m a l cells, the l a c k o f a diffuse f i b r o g e n i c stroma, and normal serum calcium and p h o s p h o r u s levels all s u p p o r t e d the diagnosis of conventional GCT. A l t h o u g h a n e u r y s m a l b o n e cyst also c o n t a i n s o s t e o c l a s t - t y p e g i a n t cells, it is c h a r a c t e r i z e d b y large vasc u l a r c h a n n e l s w h o s e walls o r s e p t a f r e q u e n t l y c o n t a i n o s t e o i d seams or t r a b e c u l a r b o n e , a n d its g i a n t cells are less n u m e r o u s a n d n o t as diffusely s c a t t e r e d as in G C T . F i n a l l y , a primary osteosarcoma with abundant o s t e o c l a s t - t y p e g i a n t cells c a n be r u l e d o u t in o u r case b e c a u s e o f the absence of osteoid or bone formed b y m a l i g n a n t s t r o m a l cells. Because o f the large size o f the tum o r a n d its e x t e n s i o n into the soft tissue, local r e c u r r e n c e w o u l d n o t be u n e x p e c t e d in o u r p a t i e n t [3, 4, 18, 31, 32]. O f m o r e concern, h o w e v e r , is the f u t u r e p o t e n t i a l for the development of a postradiation sarcoma in this p a t i e n t , the figures for w h i c h r a n g e in the l i t e r a t u r e f r o m 7 % to a l m o s t 30% f o l l o w i n g r a d i a t i o n thera p y o f G C T [3, 15, 33]. Thus, this p a t i e n t m u s t be carefully f o l l o w e d for the r e m a i n d e r o f his life for the o c c u r r e n c e o f m a l i g n a n c y within t h e field o f r a d i a t i o n . This case e m p h a sizes t h a t the d i a g n o s i s o f M G C T o f b o n e m u s t be b a s e d o n h i s t o l o g i c a l evidence a n d t h a t size, r a d i o l o g i c a l a p p e a r a n c e , a n d soft-tissue involvem e n t are n o t c o n t r o l l i n g f a c t o r s for t h a t diagnosis. In summary, a case o f the rare occ u r r e n c e o f c o n v e n t i o n a l G C T in a rib is p r e s e n t e d . D u e to its r a d i o l o g i cal aggressivity, the p o s s i b i l i t y o f a M G C T was e n t e r t a i n e d clinically, and preoperative chemotherapy and r a d i a t i o n t h e r a p y were given. T h e lite r a t u r e o n g i a n t cell t u m o r s o f the ribs is reviewed, a n d their d i s t i n c t i o n from primary MGCT and other g i a n t - c e l l - c o n t a i n i n g lesions is discussed.

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