Oral Oncology EXTRA (2006) 42, 115–122

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CASE REPORT

Maxilla tuberosity malignant fibrous histiocytomawith giant fibroblastic cells: Case reportand review of literature

K.A. Al-Salihi a,*, K.A. Al-Jashamy b, S. Ab Rahman a, A.R. Samsudin a

a School of Dental Sciences, University Sains Malaysia, 16150 HUSM, PPSG, Kubang Kerian,Kota Bharua, Kelantan, Malaysiab School of Medical Sciences, University Sains Malaysia, 16150 HUSM, PPSG, Kubang Kerian,Kota Bharua, Kelantan, Malaysia

Received 26 September 2005; accepted 28 September 2005

Summary Malignant fibrous histiocytoma (MFH) of the maxilla is a rare neoplasm. A round 61cases reported in the international literature since 1974. We present a rare case of primary MFHof the maxilla in the unusual location of maxilla in a 64-year-old man. The tumor was located inthe left tuberosity of maxilla extending from the junction between soft and hard palate towardspremolar area of edentulous ridge, and measured 7 cm · 6 cm. Histologically, it consisted ofspindle-shaped, pleomorphic malignant cells in a storiform pattern associated with histio-cyte-like cells and giant cells. Mitotic figures were frequent Immunohistochemically, most ofthe tumor cells were strongly positive for vimentin, and negative with S-100 protein, cytoker-atin, actin, desmin, HMB45 and epithelial membrane antigen. Ultra structurally, the tumor haveclearly shown spindle shaped fibroblastic and giant cells with well-known pleomorphic multi-segmented nuclei, prominent branching and often dilated rough endoplasmic reticulum(RER). Histopathological and ultra structural findings are consistent with high-grade MFH ofthe storiform/pleomorphic subtype. Four months later the patient came with residual/recur-rent tumor that was confirmed histopathologically. The literature is briefly reviewed.

�c 2005 Elsevier Ltd. All rights reserved.

KEYWORDSMaxilla;MFH;Vimentin;RER;Multi-segmented nuclei

1d

741-9409/$ - see front matter �c 2005 Elsevier Ltd. All rights reserved.oi:10.1016/j.ooe.2005.09.014

* Corresponding author. Tel.: +60 9607663749; fax: +60 9607642026.E-mail address: elsalihi@yahoo.com (K.A. Al-Salihi).

116 K.A. Al-Salihi et al.

Introduction

Arthur purdy stout, coined the term malignant fibrous histi-ocytoma, on the basis of tissue culture studies made by Mar-garet Murray, which purportedly showed that thesepleomorphic fibroblastic tumors arose from tissue histio-cytes capable of fibroblastic transformation ‘‘facultativefibroblasts’’. Enzinger and Weiss subsequently defined fivesubtypes of MFH as follows: (1) storiform-pleomorphic, (2)myxoid, (3) giant cell, (4) inflammatory, and (5) angioma-toid. MFH is the most common adult soft tissue sarcoma.1

Recently there are controversial entities regarding tumorsof fibroblastic differentiation. The ubiquitous fibroblast iscapable of a wide variety of morphologic and functionaladaptation in relation to its body site as well as local phys-iologic and pathologic changes. The active collagen synthe-sizing fibroblast is a spindle shaped or plump epithelioid cellwith prominent juxtanuclear Golgi apparatus and welldeveloped branching rough endoplasmic reticulum (RER).2

There is longstanding disagreement as to whether the celltype composing MFH is a histiocyte or a fibroblast. Initially,it was proposed by Ozzello et al.3 that the cell was ‘‘facul-tative fibroblasts’’ (a histiocyte that could appear and func-tion as a fibroblast). However, the majority of more recenthistochemical, immunohistochemical, and ultrastructuralstudies of this tumor support the contention that MFH is aform of fibrosarcoma.1,2,4,5 Previously the diagnosis is madeon the basis of the histological appearance. Recently, dis-tinction among these pleomorphic soft tissue tumors is bestachieved by a joint immunohistochemical and ultra struc-tural study.2

Malignant fibrous histiocytoma, the most common softtissue sarcoma of adults has a variety of morphologicalappearance ranging from a markedly myxoid tumor to ahypercellular, often pleomorphic neoplasms. Frequentlypresent are cell in a storiform arrangement.

Malignant fibrous histiocytomas can arise from soft tissueor bone. It’s most common in the soft tissues of the abdo-men and extremities, with 23% occur in osseous sites.Although it can be found in the head and neck region, itsoccurrence is uncommon, accounting for 3–8.5% of thecases6,7 Peak occurrence is in persons aged 50–70 years. Aslight male predominance is observed. It can occur every-where, owing to its mesenchymal origin.8,9 The most com-mon sites of occurrence in the head and neck are thesinonasal tract.10 soft tissues of the neck, craniofacialbones, and salivary glands. A literature search showedaround 61 well-documented cases of malignant fibrous histi-ocytoma arising at maxilla, maxillary sinuses and zygoma(Table 1).11–40

We describe interesting case of unusual location at lefttuberosity of maxilla tumors that had been diagnosed at avery late stage.

Report of the case

A 64-year-old Malay man presented with swelling at lefttuberosity of maxilla, which was noticed 2 months prior toseeking treatment. Lately, however the swelling was foundto be painful and easily bleed during eating. Upon examina-tion, there was a huge exophytic growth measuring

7 cm · 6 cm over the left tuberosity of maxilla extendingfrom the junction between soft and hard palate towardspremolar area of edentulous ridge (Fig. 1). The growthextended laterally from the vestibule to the midline. Clini-cally, regional lymph nodes were not palpable. Radiographicexamination showed aggressive enhances soft tissue mass atleft infratemporal space posterior to left pterygoid plate ofmaxilla. Diffuse within the lateral pterygoid muscle. Themass occupied the left part of hard palate extending topremolar area in which involving the midline. A computedtomography scan (Plain and CECT) from base of skull tothoracic inlet revealed an ill defined soft tissue masswith heterogenous enhancement noted in the left palatineregion with central non-enhancement suggestive of centralnecrosis. It measures 3.6 cm (AP) · 4.1 cm (W) · 5.0 cm(CC). Superiorly the mass extends till the nasopharynx (atC1 level) with obliteration of the right fossa of Rosen Muller.Inferiorly it extends to the level of tongue. Both parotidand submandibular glands are not involved (Fig. 2A and B).The patient underwent to left lower level partial hemimax-illectomy. A soft grayish to pinkish homogeneous tumormass measuring 8 · 7 · 3 cm was removed and submittedfor oral pathology laboratory. Unfortunately this patienthad been defaulted the radiotherapy treatment, whichwas planned earlier as adjunct to the surgery (Fig. 3). Hecame back to clinic four months later with residual/recur-rent tumor, which was confirmed histopathologically.

Materials and methods

Tumor mass was cut into small portions, some of these por-tions were fixed in 10% neutral buffered formalin, processedfor light microcopy and stained with hematoxylin and eosin.For imunohistochemical staining 4 mm thick sections fromselected paraffin block were stained with vimentin, S-100protein, cytokeratin, actin, desmin, HMB45 and epithelialmembrane antigen. For transmission electron microscopystudy, a portion of solid mass was cut into 1 mm fragments,fixed in 2.5% gluteraldehyde and post-fixed in spur resin.After examination of 1 lm survey semi-ultrathin sections,ultrathin sections were cut and stained with uranyl acetatefollowed by lead citrate. The specimen was examined bytransmission electron microscope (TEM) (Zeiss, Germany).

Results

Microscopically, the mass contained interlacing pleomor-phic mix of fibroblasts and multi-nucleated cells revealedbizarre nuclei, abundant eosinophilic cytoplasm, and abnor-mal frequent mitotic figures. Fibroblastic spindle cells ar-ranged in fascicles and myxoid pattern. Necrosis andextensive cellular atypia were also seen. Many areas re-vealed spindle cells arranged in a storiform pattern. Histio-cyte-like cells interspersed between the spindle cells(Fig. 4A and B).

Immunohistochemically, most of the tumor cells (80%)were strongly positive for vimentin (Fig. 5A and B) and neg-ative with S-100 protein, cytokeratin, actin, desmin, HMB45and epithelial membrane antigen.

Ultrastructural evaluation of the MFH revealed stori-form–pleomorphic subtype. The section consisted of spin-

Table 1 Reported cases of maxilla malignant fibrous histiocytomas (Pr—primary, Met—metastasis, Rec—recurrences, S—surgery, R—radiation, C—chemotherapy, L—regional lymphnod, DC—died of disease, AO—alive without disease, AC—alive with disease, NM—non-mentioned)

No. Author & year Case Sex Age (Year) Site of lesion Treat Rec Met Follow up Status

1. Watanabe (2005) 1 case Pr/MFH M 83 Right maxilla C+ Bounding NM NM 13 months DC2. Sabesan et al.

(2005)15 cases Pr/MFH NS Mean age

43 (13–83)Maxilla S NM NM NM NM

3. Chan et al. (2004) 1 case Pr/MFH F 44 Left maxillarymolar region

S + R � � 17 months AO

4. Yamaguchi et al. (2003) 1. Pr/MFH M 29 Max sinus S + C + � 1 year DC2. Pr/MFH M 56 Maxilla S + C + R � � 11 years,

8 monthsAO

3. Pr/MFH M 57 Max sinus S + L 9 months DC4. Pr/MFH M 63 Max sinus S + C + R � � 5 years AO

5. Sato et al. (2001) 1. Pr/MFH F 48 Left maxillarymolar region

S + +/LungMet

Severalmonths

DC

2. Pr/MFH F 47 Right maxillarypremolar regions

S + C + +/Skinbonelung

2 years DC

5. Mardinger et al. (2001) 1 case Pr/MFH/high grade F 32 Post-maxillary andalveolar ridge

S NM NM NM NM

6. Pandy et al. (2000) 1 case Pr/MFH M 54 Zygoma + Maxilla S(WE) + R R after18months

NM 77 months AO

7. Amante (1997) 1 case Pr/MFH F 40 Maxilla S + C NM NM 8 months DC8. Li et al. (1997) 1 case/after radiation M 47 Maxillary sinus S + R + NM 10 months AC/Deteriorate

condition9. Lin et al. (1994) 2 cases/after radiation NM NM Maxilla NM NM NM 17

monthsAC/Very poorafter 17 monthsurvive

10. Besly et al. (1993) 2 case s/Pr/MFH NM NM Maxilla S NM NM NM NM11. Wang (1993) 1 case/Pr/MFH F 19 Maxilla S NM NM NM NM12. Paume et al. (1993) 1 case/an anaplastic sarcomatous

zone of the malignant fibroushistiocytoma (MFH) type

F 19 Maxilla S R L NM NM

13 Namyslowski et al. (1993) 1 case/Pr/MFH F 71 Maxilla S NM NM NM NM14. Takahashi and Sato (1991) 1 case/Pr/MFH F 45 Maxilla S NM NM NM NM15. Ireland et al. (1988) 2 cases/MFH after radiation NM NM Maxilla S NM NM NM NM16. Min (1988) 1 case/Pr/MFH (article in

Korean language)17. Fan et al. (1986) 7 cases/Pr/MFH NM NM Maxilla S NM NM NM NM

Tagawa et al. (1986) 1 case/Pr/MFH NM NM Right maxilla NM NM NM NM NM18. Block et al. (1986) 1 case/Pr/MFH NM NM Maxillary sinus S NM NM NM NM19. Karcher et al. (1986) 1 case/Pr/MFH NM NM Maxilla S NM NM NM NM

(continued on next page)

Maxilla

tuberosity

malign

antfibroushistio

cytomawith

giantfibroblastic

cells

117

Table

1(continued)

No.

Author&

year

Case

Sex

Age

(Year)

Site

oflesion

Treat

Rec

Met

Follow

up

Status

20.

Shikim

ori

andOka

(1985

)1ca

se/P

r/MFH

NM

NM

Max

illa

SNM

12months

21.

Abdul-Karim

etal.(198

5)

4ca

ses/Pr/MFHan

d1ca

se/

post-irrad

iation

M&F

12to

75ye

ars

Max

illa

S+C

+L

3–13

months

AO&DC

22.

Hay

teretal.(1985

)1ca

se/P

r/MFH

NM

NM

Max

illa

S+R

NM

NM

NM

NM

23.

Nishizaw

aetal.(1985

)1ca

se/M

FH/a

fterradiation

M20

Max

illa

SNM

NM

NM

NM

24.

Kessleretal.(198

1)1ca

se/P

r/MFH

NM

NM

Left

max

illa

SNM

NM

NM

NM

25.

Sonobeetal.(198

0)1ca

se/P

r/MFH

M39

Left

Max

illa

S+C+R

+Lu

ngs,pleurae,

pan

creas,

kidneys

and

bonemarrows

1ye

arDC

26.

Sidhuetal.(197

8)

1ca

se/P

r/MFH

NM

NM

Max

illa

NM

NM

NM

NM

NM

27.

Slootw

egandMuller(197

7)

1ca

se/P

r/MFH

NM

NM

Max

illa

NM

NM

NM

NM

NM

28.

Spectoran

dOgu

ra(197

4)

1ca

se/P

r/MFH

NM

NM

Max

illa

NM

NM

NM

NM

NM

Figure 1 Photograph shows the clinical appearance of a hugeexophytic growth measuring 7 cm · 6 cm over the left tuberos-ity of maxilla extending from the junction between soft andhard palate towards premolar area of edentulous ridge.

118 K.A. Al-Salihi et al.

dle shaped and giant fibroblastic cells with markedly pleo-morphic multi-segmented nuclei, well developed branchingrough endoplasmic reticulum contained a finely granularsubstance and more electron dense material. Primarilyperipheral bundles of actin microfilaments with inter-spersed fusiform densities were also seen. Subplasmalem-mal attachment plaques, focal basal lamina-like material,and micropinocytotic vesicles were present to variable de-grees in these cells. Fibroblasts transformed into a contrac-tile myfibroblast were well identified by exposed peripheralarrays of actin microfilaments. The intermediate filamentswere found in a plenty amount and observed in the cyto-plasm of spindle fibroblast-like cells joined by rudimentarycell junction (Fig. 6A–D).

Discussion

‘‘As reflected in the World Health Organization classifica-tion of soft tissue tumors, so called malignant fibrous histi-ocytoma can no longer be regarded as a definable entity,and is now viewed as a synonym for undifferentiated pleo-morphic sarcoma.41 Malignant Fibrous histiocytoma is themost common soft tissue sarcoma, first described by Ozzeloet al. and O’Brien and Stout3,8 The storiform-pleomorphictype is the most common and is a highly cellular tumor,which can range from well differentiated to anaplastic.MFH affects individuals later in life and occurs more oftenin men, with an approximate 2:1 male:female ratio.

Maxillary MFH is very rare. It was first reported in 1974.40

The review of the literature produced 61 well-documentedcases of maxillary malignant fibrous histiocytoma (Table1)11–39 ranging in age from 12 to 83 years, with a medianage of 44.7 years. Most patients 54/61 (88.5%) showed clin-ical signs of primary maxillary MFH. MFH can also arise in thesite of previous radiation. However, radiation induced MFHof the head and neck is exceedingly rare. A literature searchshowed only 7/61 cases (11.47%) of post-radiation maxillaMFH.19,20,26,33,35 The sinonasal tract has been reported tobe the commonest site (30%) of tumor involvement in the

Figure 2 (A) and (B): computed tomography revealed an ill defined soft tissue mass with heterogeneous enhancement noted in theleft palatine region with central non-enhancement suggestive of central necrosis.

Figure 3 Photograph shows surgical location 10 days post-operation.

Figure 4 Photomicrographs reveal histological features ofmalignant fibrous histiocytoma: (A) low power magnification ofhistopathology showing a markedly cellular spindle-cell neo-plasm with a diffuse growth pattern reveals multiple dissem-inated nodular cellular masses (·100) and (B) high-powermagnification showing nuclear pleomorphism and mitotic activ-ity. Note the histiocyte (arrow) with an indented nucleus andabundant cytoplasm (·200).

Maxilla tuberosity malignant fibrous histiocytoma with giant fibroblastic cells 119

head and neck region.10 But Sabesan et al.12 found thatmaxilla is the most common site (15/54 cases). Thisliterature review of Maxilla MFH revealed that 41/61 cases(67.2%) of the lesions were located in maxilla11–15,17,18,20–30,32–40 while, only 5/61 cases (8.19%) in maxillarysinus,14,19,30 and only two cases (3.2%) reported in post-maxillary and alveolar ridge16 and in zygoma17 respectively.

Our patient showed painful, easily bleed swelling at lefttuberosity of maxilla. The lesion appeared as primary hugeexophytic growth measuring 7 cm · 6 cm over the lefttuberosity of maxilla extending from the junction betweensoft and hard palate towards premolar area of edentulousridge. The growth extended laterally from the vestibule tothe midline. This case presented uncommon location hasnot reported previously in literature.

Few reports have dealt with the radiographic findings ofMFH.42–44 Reported radiographic findings were irregularbone margin, a moth-eaten appearance, erosion of cortex,pathological fracture, and tooth root resorption. Although,these radiographical findings are not specific to MFH, andare usually also observed in squamous cell carcinoma, themost common malignant tumor of the head and neck. Radio-graphical evaluation of two cases MFH affecting maxillaryalveolar bone had been described by Sato et al.15 They rep-resented in details the radiographical findings, which haveseldom been described in previous reports. They reportedthe following findings, the presence of fairly well demar-cated bone destruction in the intraoral radiograph, the rel-atively smooth surface, uniform density, or no necrotic areaof the tumor. In computed tomography images, tumorshowed clear separation of the tumor from surrounding softtissues bone scintigraphs reflecting the periosteal reactionto tumor invasion and lymphoscintigraphy of the metastaticlymph nodes.15 Generally MFH of the maxilla dose not differfrom tumors arising in flat bones in other parts of the skel-eton. In our case, CT scan revealed an ill defined soft tissuemass with heterogeneous enhancement noted in the leftpalatine region with central non-enhancement suggestiveof central necrosis. These findings are different from thefinding described previously.15

Most maxilla MFH exhibited a broad range of histologicalpatterns. Information regarding histological type was avail-able in cases reviewed from literature. Storiform-pleomor-phic was the prominent type in most cases. One caserevealed an anaplastic sarcomatous zone of the malignantfibrous histiocytoma (MFH) type.23 However, only one case

Figure 6 Transmission electron microscopy photomicrographs, revealed storiform and pleomorphic MFH: (A) large fibroblastictumor cell with prominent periphery filaments with pleomorphic nucleus, (B) histiocyte revealed multi-segmented nucleus anddilated RER, (C) giant cell tumor revealed significant accumulation of vimentin intermediate filaments and (D) histiocytes revealedgiant nucleus with RER containing a finely granular substance and a more electron dense material.

Figure 5 Photomicrographs of immunohistochemically, most of the tumor cells were strongly positive for vimentin: (A) low powermagnification (·200) and (B) high-power magnification (·400).

120 K.A. Al-Salihi et al.

showed Pr/MFH/High grade.16 Our patient showed typical astoriform pattern, contained interlacing a mix of pleomor-phic fibroblasts and multi-nucleated cells arranged infascicles and myxoid pattern The cells revealed abnormalhigh mitotic index. We suggested high grade of storiformMFH. Nevertheless, the term MFH is widely used in routinepathological practice for pleomorphic soft tissue sarcomawithout specific line of differentiation. MFH is included inthe category of fibrohistiocytic tumors. The presence of alarge number of histiocyte-like or histiocytic cells in thepleomorphic sarcoma raised the question of biphasic(fibroblastic–myofibroblastic and histiocytic) differen-tiation.4,14

The trend for some pathologists to diagnose malignant fi-brous histiocytoma (MFH) less frequently than others mayresult from different diagnostic criteria for MFH amongpathologists, reflecting the concept of MFH as a commonmorphological manifestation of a variety of poorly differen-tiated sarcomas, and the diagnosis of MFH through a processof exclusion.45,46 It was concluded that a re-evaluation ofthe diagnostic criteria was essential for so called MFH.‘‘Ultrastructural observation of neoplastic cells suggeststhat the expression of smooth muscle markers in so calledmalignant fibrous histiocytoma is a result of myofibroblasticdifferentiation’’. Smooth muscle markers, such as smoothmuscle actin (SMA) and occasionally even desmin, have

Maxilla tuberosity malignant fibrous histiocytoma with giant fibroblastic cells 121

been demonstrated immunohistochemically in a subset of‘‘MFH’’. In this situation, the distinction between leiomyo-sarcoma and ‘‘MFH’’ becomes more difficult. Ultrastruc-tural observation of neoplastic cells suggests that theexpression of smooth muscle markers in ‘‘MFH’’ is a resultof myofibroblastic differentiation.47–49 There are limiteddata on the frequency and degree of positively for smoothmuscle markers in a large number of ‘‘MFHs’’.

A cases reported in literature demonstrated that mostcases were positive for vimentin and only few cases were po-sitive for cytokeratin and desmin. In our case tumor was neg-ative for epithelial markers, protein S-100 (a marker ofmelanoma and schwann cell tumor) and desmin (smoothmuscle markers). But it was strong positive for vimentin(mesenchymal markers). More recent histochemical, immu-nohistochemical, and ultra structural studies of MFH supportthe contention that MFH is a form of fibrosarcoma and the tu-mor is very likely over diagnosed. This is because the morepleomorphic the tumor the more difficult is to distinguishfrom other types of sarcomas, such as pleomorphic leiomyo-sarcoma, pleomorphic liposarcoma and dedifferentiated lip-osarcoma. Distinction among these pleomorphic soft tissuetumors is best achieved by a joint immunohistochemicaland ultrastructural study.2 Commonly, ultra structural find-ings of MFH have demonstrated that tumor cells were com-posed of fibroblast-like cells with abundant RER,histiocyte-like cells with numerous lysosomes, and transi-tional cells with characteristics of both the fibroblast-likeand histiocyte-like cell.50 Our present electron microscopicobservations compatible with typical ultra structural find-ings reported previously. It revealed spindly or stellate fibro-blast with long thin cytoplasmic processes as a cellularcollagen sparse and giant fibroblastic cells with markedlypleomorphic multi-segmented nuclei and well developedbranching RER, primarily peripheral bundles of actin micro-filaments with interspersed fusiform densities. In responseto inflammation and injury, the fibroblast often transformsinto contractile myfibroblast with peripheral arrays of actinmicrofilaments and/or a fibrohistocytes with prominent lyso-some that is often mistaken for a true histocytes. Althoughthe histocytes in MFH are though by some to be neoplastic,the origin of both histocyte-like cells and multi-nucleatedgiant cells in MFH has been the subject of much debate.51

Most of the cases 54/61 (88.5%) reported in literature re-view were treated surgically. In 4/61 (6.5%) cases, surgerywas followed with post-operative radiotherapy and in other4/61 (6. 5%) cases was followed with post-operative chemo-therapy. While in 3/61 (4.9%) cases radiotherapy and che-motherapy had been used. Only one case was treated withchemotherapy and bounding, which resulted in a largereduction tumor size without surgery.12 The proportion oflocal recurrence rate of MFH after initial local excisionranges between 16% and 52%.52,53 The presences of positivesurgical margins after definitive treatment is the single mostimportant factor relating to local recurrence.52 Accordingto Barnes and Kanbour,54 80% of patients with local recur-rences after incomplete surgical treatment subsequentlydie from disease. Recurrence is related to size, depth ofinvasion, and microscopically positive surgical margins.From the review of literature we found 9/61 (14.7%) recur-rent cases and 3/61 (4.9%) non-recurrent cases while othercases, they did not mentioned about the recurrence. In 6/61

(9.8%) cases of maxilla MFH reported metastasized distantlyto lung, skin, local, bone, pleurae, pancreas, kidneys andbone marrows.5,23,33,37 Only 6/61 (9.8%) cases survived without disease while all other case died with disease or livedwith deteriorates condition. In our case the patient came4 months later with recurrence lesion confirmed histopatho-logically.

In conclusion, we believe that MFH of the maxilla mayhave poorer prognosis than those tumors in the other partsof the maxillofacial skeleton. Size, depth, histopathologicfeatures, immunohistochemistry and ultrastructural fea-tures, surgical margin status and adjuvant radiotherapy orchemotherapy are the most important predictors ofoutcome.

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