- Email: [email protected]
Soft tissue giant cell tumor of low malignant potential with 3 localizations: report of a case
Accepted Manuscript Soft tissue giant cell tumor (GCT-ST) of low malignant potential with three localizations: report of a case Stefano Righi, M.D. Paolo Boffano, M.D. Roberta Patetta, M.D Laura Malvè, M.D. Dimitrios Pateras, M.D. Pierluigi De Matteis, M.D. Domenico Chiodo, M.D. Maurizio Boson, M.D. PII:
S2212-4403(14)00413-1
DOI:
10.1016/j.oooo.2014.03.013
Reference:
OOOO 888
To appear in:
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Received Date: 22 December 2013 Revised Date:
10 March 2014
Accepted Date: 17 March 2014
Please cite this article as: Righi S, Boffano P, Patetta R, Malvè L, Pateras D, De Matteis P, Chiodo D, Boson M, Soft tissue giant cell tumor (GCT-ST) of low malignant potential with three localizations: report of a case, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology (2014), doi: 10.1016/ j.oooo.2014.03.013. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Title: Soft tissue giant cell tumor (GCT-ST) of low malignant potential with three localizations: report of a case.
Authors: Stefano Righi M.D. *, Paolo Boffano M.D. *, Roberta Patetta M.D**, Laura Malvè M.D.
RI PT
*, Dimitrios Pateras M.D. *, Pierluigi De Matteis M.D. *, Domenico Chiodo M.D. *, Maurizio Boson M.D. *
M AN U
** Division of Pathology, Aosta Hospital, Aosta, Italy
SC
* Division of Otolaryngology, Maxillofacial Surgery and Dentistry, Aosta Hospital, Aosta, Italy
Address correspondence and reprint requests to Dr Paolo Boffano: E-mail address:
TE D
[email protected]
No disclosures
EP
RUNNING TITLE: Soft tissue giant cell tumor
AC C
KEYWORDS: Soft tissue giant cell tumor; giant cell tumor; head and neck; lip; surgery. Abstract word count: 109
Manuscript word count: 1128 Number of references: 21 Number of figures: 4 Number of tables: 1
ACCEPTED MANUSCRIPT ABSTRACT: Soft tissue giant cell tumor (GCT-ST) of low malignant potential, also called primary giant cell tumor of soft tissue, is usually located in the lower extremities and trunk, whereas it is extremely rare in the head and neck region. It is a rare neoplasm involving both superficial and deep soft
RI PT
tissues that mainly affects young to middle-age adults, presenting as an asymptomatic, wellcircumscribed multinodular mass covered by normal skin or with a fleshy red-brown surface when superficially located.
SC
The purpose of this article is to report a case of osteoclast-like giant cell tumors of the lip and to
AC C
EP
TE D
M AN U
review the literature about GCT-STs involving the head and neck region.
ACCEPTED MANUSCRIPT INTRODUCTION Soft tissue giant cell tumor (GCT-ST) of low malignant potential, also called primary giant cell tumor of soft tissue, is usually located in the lower extremities and trunk, whereas it is extremely rare in the head and neck region.1-21 It is a rare neoplasm involving both superficial and deep soft
RI PT
tissues that mainly affects young to middle-age adults, presenting as an asymptomatic, wellcircumscribed multinodular mass covered by normal skin or with a fleshy red-brown surface when superficially located. 1,2
SC
Histologically, GCT-ST is similar to the giant cell tumor of bone, with a mixture of uniformly scattered osteoclast-like giant cells and oval to polygonal mononuclear cells intermingled with short
M AN U
fascicles of spindled cells. The immunohistochemical profile of GCT-ST shows CD68 positivity, mainly in the osteoclast-like cells and focally in the mononuclear stromal cells. 1,2,6 Although GCT of soft tissues usually has a favorable natural history, it often persists unless it is excised with adequate surgical margins.7 GCT-ST has also been considered a low-grade soft tissue
TE D
sarcoma:2 however, it has a moderate local recurrence rate of approximately 15%, most likely reflecting the multinodular growth pattern exhibited by most cases, but metastases are extremely uncommon.3 In fact, today, GCT-STs are included in the group of socalled fibrohistiocytic tumors
of soft tissue tumors.8,9
EP
of intermediate (borderline) malignancy according to the World Health Organization classification
AC C
The purpose of this article is to report a case of osteoclast-like giant cell tumors of the lip and to review the literature about GCT-STs involving the head and neck region.
CASE REPORT A 36-year-old woman was referred to our outpatient clinic for the assessment of a painless cystic mass in correspondence of the inferior lip. The patient reported the lesion had been present for
ACCEPTED MANUSCRIPT several months, but it began to grow more rapidly in the last weeks. Past medical history was unremarkable. Clinical examination revealed a non-infiltrative, hard, superficially located, 1.5 cm mass in the lower lip. Therefore, the patient underwent an incisional biopsy.
RI PT
Histologically, the lesion showed a proliferation of spindle cells admixed with giant osteoclasticlike multinucleated cells with mild to moderate nuclear atypia.
Immunohistochemically, the osteoclast-like giant cells showed positive immunoreactivity for
SC
vimentin, CD68 and actin, whereas cells were negative for CD34, EMA, S-100, Cytokeratins, AE1/AE3, Desmin, and LCA. The Ki-67 labeling index was approximately 15%. (Figures 1 -2)
cell tumor of low malignant potential.
M AN U
The pathological interpretation of the biopsy results suggested the diagnosis of a soft tissue giant
In the meanwhile, the patient complained of a new 0.5 cm mass arising in the subcutaneous tissues of the anterior tibial region. A PET-CT confirmed two pathological localizations in correspondence
TE D
of lower lip and subcutaneous anterior tibial region. The anterior tibial lesion was widely excised with a pathological diagnosis of soft tissue giant cell tumor of low malignant potential. Finally, the patient underwent surgical intervention of wide excision of the tumor in correspondence
EP
of the inferior lip. Definitive pathological examination confirmed the previous diagnosis. Postoperative course was uneventful.
AC C
Six months after surgery the patient performed a PET-CT that showed the presence of a possible lesion in correspondence of the gluteus with a suspect of a further localization of the soft tissue giant cell tumor of low malignant potential. (Figure 3) Therefore, the patient underwent a surgical intervention of excision of the lesion that confirmed the hypothesized diagnosis. (Figure 4) The patient is currently followed up and no further recurrence or secondary localization have been observed. This article was exempt from IRB approval. We followed Helsinki Declaration guidelines.
ACCEPTED MANUSCRIPT DISCUSSION Soft tissue giant cell tumor of low malignant potential is an uncommon but distinct entity occurring primarily in the superficial and deep soft tissues of the extremities that resemble giant cell tumor of bone with multinodular aggregates.5 Primary GCT of soft tissues does not show age or sex
RI PT
predilection.9 Rare cases have been reported in the head and neck region. (Table 1)
This tumor has a biologically benign behavior, although the infiltrative growth pattern can involve deep delicate anatomical structures such as the neurovascular bundles, sometimes making complete
SC
surgical excision difficult and recurrences possible. 1,4
GCT-STs present as painless growing masses, with an average duration of symptoms of 6 months.
M AN U
Peripheral mineralization is exceedingly frequent in GCT-ST, that have a characteristic radiographic appearance.8
Most GCT-STs display a multinodular architecture, with the cellular nodules being separated by fibroconnective tissue septa of varying thickness and containing haemosiderin-laden macrophages.
TE D
The nodules are composed of a mixture of round to oval cells that are mononuclear and osteoclastlike giant cells that are multinucleated, with both cell types immersed in a richly vascularised stroma.8
EP
Mitotic activity generally is present in every GCT-ST, typically ranging from 1 to 30 figures per 10 high-power fields. Atypia, pleomorphism, and tumoural giant cells are absent, and areas of necrosis
AC C
are only focally present.6,8,9 Other degenerative changes such as stromal hemorrhage, hemosiderin deposition, and aneurysmal bone cyst-like changes can be observed too.6 GCT-STs usually show an immunohistochemical staining profile similar to GCT of bone, displaying immunoreactivity for vimentin, CD68, and smooth muscle actin. CD68 strongly marks the multinucleated giant cells; the mononuclear cells show focal staining only.8,9 Histologically, the differential diagnosis is broad, so it is advisable to plan treatment as clinical behavior and prognosis significantly differ. In fact, differential diagnosis should include benign lesions (such as GCT of tendon sheaths, cellular dermatofibroma with osteoclast-like giant cells,
ACCEPTED MANUSCRIPT ossifying dermatofibroma with osteoclast-like giant cells, reparative giant cell granuloma, nodular fasciitis, and brown tumor of hyperparathyroidism extending to soft tissues) and malignant lesions ( leiomyosarcoma with osteoclast- like giant cells, epithelioid sarcoma with giant cells, extra-skeletal osteosarcoma, atypical fibroxanthoma with osteoclast-like giant cells, and plexiform fibrohistiocytic
RI PT
tumor).1,4,7,9
In the literature, complete removal of the GCT-ST with negative surgical margins is advised.7 However, the incidence of local recurrence is high, with a 28% recurrence rate in skin and 45 % in
SC
deep soft tissue. Furthermore, distant metastasis are possible, as in our case, although in previous reports they were all in the lungs.1,7
M AN U
As for radiotherapy, no solid evidence is still available but it can be considered when the proximity of critical structures prevents clear surgical margins.7
TE D
CONCLUSION
GCT-ST is a tumor with low malignant potential and it should be considered in the differential diagnosis of giant cell-rich soft tissue neoplasms. Even if GCT-ST is completely excised with
EP
negative surgical margins, a strict follow up is recommended, as local and distant recurrences are
AC C
possible in the first years.
ACCEPTED MANUSCRIPT REFERENCES: 1. Boneschi V, Parafioriti A, Armiraglio E, Gaiani F, Brambilla L. Primary giant cell tumor of soft tissue of the groin - a case of 46 years duration. J Cutan Pathol. 2009;36 Suppl 1:20-4. 2. Albores-Saavedra J, Grider DJ, Wu J, Henson DE, Goodman ZD. Giant cell tumor of the extrahepatic biliary tree: a clinicopathologic study of 4 cases and comparison with
RI PT
anaplastic spindle and giant cell carcinoma with osteoclast-like giant cells. Am J Surg Pathol. 2006;30:495-500
3. Grabellus F, von Winterfeld F, Sheu SY, Metz KA, Jahnke K, Schmid KW. Unusual aggressive course of a giant cell tumor of soft tissue during immunosuppressive therapy.
SC
Virchows Arch. 2006;448:847-51.
4. Dodd LG, Major N, Brigman B. Malignant giant cell tumor of soft parts Skeletal Radiol.
M AN U
2004;33:295-9.
5. Holst VA, Elenitsas R. Primary giant cell tumor of soft tissue. J Cutan Pathol. 2001; 28: 492-5.
6. Guo H, Garcia RA, Perle MA, Amodio J, Greco MA. Giant cell tumor of soft tissue with pulmonary metastases: pathologic and cytogenetic study. Pediatr Dev Pathol. 2005;8:71824.
Clin Med. 2004;29:91-5.
TE D
7. Icihikawa K, Tanino R. Soft tissue giant cell tumor of low malignant potential. Tokai J Exp
8. Fletcher CDM, Unni K, Mertens F. Pathology and Genetics of Tumours of Soft Tissue and Bone. WHO Classification of Tumours. Lyon, France: IARC Press; 2002:310–313.
EP
9. Lentini M, Zuccalà V, Fazzari C. Polypoid giant cell tumor of the skin. Am J Dermatopathol. 2010;32:95-8.
AC C
10. Angervall L, Hagmar B, Kindblom LG, Merck C. Malignant giant cell tumor of soft tissues: a clinicopathologic, cytologic, ultrastructural, angiographic, and microangiographic study. Cancer. 1981;47:736-47. 11. Guccion JG, Enzinger FM. Malignant giant cell tumor of soft parts. An analysis of 32 cases. Cancer. 1972;29:1518-29. 12. Maheswaran P, Addis BJ. Osteoclastoma-like giant cell tumour of the skin. Histopathology. 1990;16:604-7. 13. Hoang MP, Rogers BB, Albores-Saavedra J. Giant cell tumor of the skin: a morphologic and immunohistochemical study of five cases. Ann Diagn Pathol. 2002;6:288-93.
ACCEPTED MANUSCRIPT 14. Oliveira AM, Dei Tos AP, Fletcher CD, Nascimento AG. Primary giant cell tumor of soft tissues: a study of 22 cases. Am J Surg Pathol. 2000;24:248-56. 15. Pepper T, Falla L, Brennan PA. Soft tissue giant cell tumour of low malignant potential arising in the masseter--a rare entity in the head and neck. Br J Oral Maxillofac Surg. 2010;48:149-51.
RI PT
16. Torabinezad S, Kumar PV, Hashemi SB, Rahimi A. Osteoclastomalike giant cell tumor of the parotid gland: report of a case with fine needle aspiration diagnosis. Acta Cytol. 2006;50:80-3.
17. Tuluc M, Zhang X, Inniss S. Giant cell tumor of the nasal cavity: case report. Eur Arch
SC
Otorhinolaryngol. 2007;264:205-8.
18. Wu CJ, Wu PH, Chu ST, Yu WW, Chen PC. Features of a giant cell tumour of the parotid gland: A case report. Oncol Lett. 2013;6:829-832.
M AN U
19. Gulavani N, Selavraju K. Primary Soft Tissue Giant Cell Tumor Of Neck. WebmedCentral general surgery 2010;1(10):WMC00901
20. Callı AO, Tunakan M, Katilmiş H, Kilçiksiz S, Oztürkcan S. Soft tissue giant cell tumor of low malignant potential of the neck: a case report and review of the literature. Turk Patoloji Derg. 2014;30(1):73-77.
TE D
21. Goze OF, Muslehiddinoğlu A. Primary giant cell tumor of soft tissue on mandibular region:
AC C
EP
a case report and literature review. Basic Clin Sci 2013;2:71-82
RI PT
ACCEPTED MANUSCRIPT
LEGENDS:
SC
Figure 1: Histological image of lip giant cell tumor of soft tissue (EE 10 x) Figure 2: CD68 immunohistochemical staining of the lip giant cell tumor.
M AN U
Figure 3: CT-PET images of the gluteus localization of the giant cell tumor of soft tissue. Figure 4: Histological image of the giant cell tumor of soft tissue in correspondence of the gluteus
AC C
EP
TE D
(EE 10 x)
ACCEPTED MANUSCRIPT TABLE 1. Clinicopathologic features of giant cell tumours of soft tissues with a head and neck localization.
Year 1981
Age 75
Sex M
Location neck
Size 3 cm
Treatment Local excision
Grabellus et al3
2006
73
M
Temporal forehead
1 cm
surgically resected
Guccion and Enzinger11
1972
33
F
Right face
2.5 cm
Maheswaran 1990 and Addis12
92
F
cheek
2.7 cm
2002
73
M
forehead
1 cm
Lentini et al9
2010
79
F
Oliveira et al14 Pepper et al15
2000
9
M
Right paranasal region skin neck
2010
59
F
Torabinezad et al16 Tuluc et al17
2006
35
1.5 cm
Wide excision excision
na
na
na
masseter
2 cm
na
F
parotid
1.5 cm
Incomplete excision + adiuvant radiotherapy (45 Gy in 20 fractions) excision
na
Nasal cavity parotid
0.7 cm
excision
NED
4 cm
Incomplete excision + adiuvant radiotherapy (64 Gy in 32 fractions)
NED
EP
AC C
Wu et al 18
TE D
13
2007
32
F
2013
58
M
SC
M AN U
Hoang et al
Follow-Up Died after 1% years with multiple subcutaneous tumors and lung metastases two tumor relapses of the GCT-ST after 6 and 11 months. Alive 1 local recurrence. Alive No recurrence. NED Alive Lost to follow-up NED
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Author Angervall et al10
Radical excision
Wide excision
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EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
S2212-4403(14)00413-1
DOI:
10.1016/j.oooo.2014.03.013
Reference:
OOOO 888
To appear in:
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Received Date: 22 December 2013 Revised Date:
10 March 2014
Accepted Date: 17 March 2014
Please cite this article as: Righi S, Boffano P, Patetta R, Malvè L, Pateras D, De Matteis P, Chiodo D, Boson M, Soft tissue giant cell tumor (GCT-ST) of low malignant potential with three localizations: report of a case, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology (2014), doi: 10.1016/ j.oooo.2014.03.013. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Title: Soft tissue giant cell tumor (GCT-ST) of low malignant potential with three localizations: report of a case.
Authors: Stefano Righi M.D. *, Paolo Boffano M.D. *, Roberta Patetta M.D**, Laura Malvè M.D.
RI PT
*, Dimitrios Pateras M.D. *, Pierluigi De Matteis M.D. *, Domenico Chiodo M.D. *, Maurizio Boson M.D. *
M AN U
** Division of Pathology, Aosta Hospital, Aosta, Italy
SC
* Division of Otolaryngology, Maxillofacial Surgery and Dentistry, Aosta Hospital, Aosta, Italy
Address correspondence and reprint requests to Dr Paolo Boffano: E-mail address:
TE D
[email protected]
No disclosures
EP
RUNNING TITLE: Soft tissue giant cell tumor
AC C
KEYWORDS: Soft tissue giant cell tumor; giant cell tumor; head and neck; lip; surgery. Abstract word count: 109
Manuscript word count: 1128 Number of references: 21 Number of figures: 4 Number of tables: 1
ACCEPTED MANUSCRIPT ABSTRACT: Soft tissue giant cell tumor (GCT-ST) of low malignant potential, also called primary giant cell tumor of soft tissue, is usually located in the lower extremities and trunk, whereas it is extremely rare in the head and neck region. It is a rare neoplasm involving both superficial and deep soft
RI PT
tissues that mainly affects young to middle-age adults, presenting as an asymptomatic, wellcircumscribed multinodular mass covered by normal skin or with a fleshy red-brown surface when superficially located.
SC
The purpose of this article is to report a case of osteoclast-like giant cell tumors of the lip and to
AC C
EP
TE D
M AN U
review the literature about GCT-STs involving the head and neck region.
ACCEPTED MANUSCRIPT INTRODUCTION Soft tissue giant cell tumor (GCT-ST) of low malignant potential, also called primary giant cell tumor of soft tissue, is usually located in the lower extremities and trunk, whereas it is extremely rare in the head and neck region.1-21 It is a rare neoplasm involving both superficial and deep soft
RI PT
tissues that mainly affects young to middle-age adults, presenting as an asymptomatic, wellcircumscribed multinodular mass covered by normal skin or with a fleshy red-brown surface when superficially located. 1,2
SC
Histologically, GCT-ST is similar to the giant cell tumor of bone, with a mixture of uniformly scattered osteoclast-like giant cells and oval to polygonal mononuclear cells intermingled with short
M AN U
fascicles of spindled cells. The immunohistochemical profile of GCT-ST shows CD68 positivity, mainly in the osteoclast-like cells and focally in the mononuclear stromal cells. 1,2,6 Although GCT of soft tissues usually has a favorable natural history, it often persists unless it is excised with adequate surgical margins.7 GCT-ST has also been considered a low-grade soft tissue
TE D
sarcoma:2 however, it has a moderate local recurrence rate of approximately 15%, most likely reflecting the multinodular growth pattern exhibited by most cases, but metastases are extremely uncommon.3 In fact, today, GCT-STs are included in the group of socalled fibrohistiocytic tumors
of soft tissue tumors.8,9
EP
of intermediate (borderline) malignancy according to the World Health Organization classification
AC C
The purpose of this article is to report a case of osteoclast-like giant cell tumors of the lip and to review the literature about GCT-STs involving the head and neck region.
CASE REPORT A 36-year-old woman was referred to our outpatient clinic for the assessment of a painless cystic mass in correspondence of the inferior lip. The patient reported the lesion had been present for
ACCEPTED MANUSCRIPT several months, but it began to grow more rapidly in the last weeks. Past medical history was unremarkable. Clinical examination revealed a non-infiltrative, hard, superficially located, 1.5 cm mass in the lower lip. Therefore, the patient underwent an incisional biopsy.
RI PT
Histologically, the lesion showed a proliferation of spindle cells admixed with giant osteoclasticlike multinucleated cells with mild to moderate nuclear atypia.
Immunohistochemically, the osteoclast-like giant cells showed positive immunoreactivity for
SC
vimentin, CD68 and actin, whereas cells were negative for CD34, EMA, S-100, Cytokeratins, AE1/AE3, Desmin, and LCA. The Ki-67 labeling index was approximately 15%. (Figures 1 -2)
cell tumor of low malignant potential.
M AN U
The pathological interpretation of the biopsy results suggested the diagnosis of a soft tissue giant
In the meanwhile, the patient complained of a new 0.5 cm mass arising in the subcutaneous tissues of the anterior tibial region. A PET-CT confirmed two pathological localizations in correspondence
TE D
of lower lip and subcutaneous anterior tibial region. The anterior tibial lesion was widely excised with a pathological diagnosis of soft tissue giant cell tumor of low malignant potential. Finally, the patient underwent surgical intervention of wide excision of the tumor in correspondence
EP
of the inferior lip. Definitive pathological examination confirmed the previous diagnosis. Postoperative course was uneventful.
AC C
Six months after surgery the patient performed a PET-CT that showed the presence of a possible lesion in correspondence of the gluteus with a suspect of a further localization of the soft tissue giant cell tumor of low malignant potential. (Figure 3) Therefore, the patient underwent a surgical intervention of excision of the lesion that confirmed the hypothesized diagnosis. (Figure 4) The patient is currently followed up and no further recurrence or secondary localization have been observed. This article was exempt from IRB approval. We followed Helsinki Declaration guidelines.
ACCEPTED MANUSCRIPT DISCUSSION Soft tissue giant cell tumor of low malignant potential is an uncommon but distinct entity occurring primarily in the superficial and deep soft tissues of the extremities that resemble giant cell tumor of bone with multinodular aggregates.5 Primary GCT of soft tissues does not show age or sex
RI PT
predilection.9 Rare cases have been reported in the head and neck region. (Table 1)
This tumor has a biologically benign behavior, although the infiltrative growth pattern can involve deep delicate anatomical structures such as the neurovascular bundles, sometimes making complete
SC
surgical excision difficult and recurrences possible. 1,4
GCT-STs present as painless growing masses, with an average duration of symptoms of 6 months.
M AN U
Peripheral mineralization is exceedingly frequent in GCT-ST, that have a characteristic radiographic appearance.8
Most GCT-STs display a multinodular architecture, with the cellular nodules being separated by fibroconnective tissue septa of varying thickness and containing haemosiderin-laden macrophages.
TE D
The nodules are composed of a mixture of round to oval cells that are mononuclear and osteoclastlike giant cells that are multinucleated, with both cell types immersed in a richly vascularised stroma.8
EP
Mitotic activity generally is present in every GCT-ST, typically ranging from 1 to 30 figures per 10 high-power fields. Atypia, pleomorphism, and tumoural giant cells are absent, and areas of necrosis
AC C
are only focally present.6,8,9 Other degenerative changes such as stromal hemorrhage, hemosiderin deposition, and aneurysmal bone cyst-like changes can be observed too.6 GCT-STs usually show an immunohistochemical staining profile similar to GCT of bone, displaying immunoreactivity for vimentin, CD68, and smooth muscle actin. CD68 strongly marks the multinucleated giant cells; the mononuclear cells show focal staining only.8,9 Histologically, the differential diagnosis is broad, so it is advisable to plan treatment as clinical behavior and prognosis significantly differ. In fact, differential diagnosis should include benign lesions (such as GCT of tendon sheaths, cellular dermatofibroma with osteoclast-like giant cells,
ACCEPTED MANUSCRIPT ossifying dermatofibroma with osteoclast-like giant cells, reparative giant cell granuloma, nodular fasciitis, and brown tumor of hyperparathyroidism extending to soft tissues) and malignant lesions ( leiomyosarcoma with osteoclast- like giant cells, epithelioid sarcoma with giant cells, extra-skeletal osteosarcoma, atypical fibroxanthoma with osteoclast-like giant cells, and plexiform fibrohistiocytic
RI PT
tumor).1,4,7,9
In the literature, complete removal of the GCT-ST with negative surgical margins is advised.7 However, the incidence of local recurrence is high, with a 28% recurrence rate in skin and 45 % in
SC
deep soft tissue. Furthermore, distant metastasis are possible, as in our case, although in previous reports they were all in the lungs.1,7
M AN U
As for radiotherapy, no solid evidence is still available but it can be considered when the proximity of critical structures prevents clear surgical margins.7
TE D
CONCLUSION
GCT-ST is a tumor with low malignant potential and it should be considered in the differential diagnosis of giant cell-rich soft tissue neoplasms. Even if GCT-ST is completely excised with
EP
negative surgical margins, a strict follow up is recommended, as local and distant recurrences are
AC C
possible in the first years.
ACCEPTED MANUSCRIPT REFERENCES: 1. Boneschi V, Parafioriti A, Armiraglio E, Gaiani F, Brambilla L. Primary giant cell tumor of soft tissue of the groin - a case of 46 years duration. J Cutan Pathol. 2009;36 Suppl 1:20-4. 2. Albores-Saavedra J, Grider DJ, Wu J, Henson DE, Goodman ZD. Giant cell tumor of the extrahepatic biliary tree: a clinicopathologic study of 4 cases and comparison with
RI PT
anaplastic spindle and giant cell carcinoma with osteoclast-like giant cells. Am J Surg Pathol. 2006;30:495-500
3. Grabellus F, von Winterfeld F, Sheu SY, Metz KA, Jahnke K, Schmid KW. Unusual aggressive course of a giant cell tumor of soft tissue during immunosuppressive therapy.
SC
Virchows Arch. 2006;448:847-51.
4. Dodd LG, Major N, Brigman B. Malignant giant cell tumor of soft parts Skeletal Radiol.
M AN U
2004;33:295-9.
5. Holst VA, Elenitsas R. Primary giant cell tumor of soft tissue. J Cutan Pathol. 2001; 28: 492-5.
6. Guo H, Garcia RA, Perle MA, Amodio J, Greco MA. Giant cell tumor of soft tissue with pulmonary metastases: pathologic and cytogenetic study. Pediatr Dev Pathol. 2005;8:71824.
Clin Med. 2004;29:91-5.
TE D
7. Icihikawa K, Tanino R. Soft tissue giant cell tumor of low malignant potential. Tokai J Exp
8. Fletcher CDM, Unni K, Mertens F. Pathology and Genetics of Tumours of Soft Tissue and Bone. WHO Classification of Tumours. Lyon, France: IARC Press; 2002:310–313.
EP
9. Lentini M, Zuccalà V, Fazzari C. Polypoid giant cell tumor of the skin. Am J Dermatopathol. 2010;32:95-8.
AC C
10. Angervall L, Hagmar B, Kindblom LG, Merck C. Malignant giant cell tumor of soft tissues: a clinicopathologic, cytologic, ultrastructural, angiographic, and microangiographic study. Cancer. 1981;47:736-47. 11. Guccion JG, Enzinger FM. Malignant giant cell tumor of soft parts. An analysis of 32 cases. Cancer. 1972;29:1518-29. 12. Maheswaran P, Addis BJ. Osteoclastoma-like giant cell tumour of the skin. Histopathology. 1990;16:604-7. 13. Hoang MP, Rogers BB, Albores-Saavedra J. Giant cell tumor of the skin: a morphologic and immunohistochemical study of five cases. Ann Diagn Pathol. 2002;6:288-93.
ACCEPTED MANUSCRIPT 14. Oliveira AM, Dei Tos AP, Fletcher CD, Nascimento AG. Primary giant cell tumor of soft tissues: a study of 22 cases. Am J Surg Pathol. 2000;24:248-56. 15. Pepper T, Falla L, Brennan PA. Soft tissue giant cell tumour of low malignant potential arising in the masseter--a rare entity in the head and neck. Br J Oral Maxillofac Surg. 2010;48:149-51.
RI PT
16. Torabinezad S, Kumar PV, Hashemi SB, Rahimi A. Osteoclastomalike giant cell tumor of the parotid gland: report of a case with fine needle aspiration diagnosis. Acta Cytol. 2006;50:80-3.
17. Tuluc M, Zhang X, Inniss S. Giant cell tumor of the nasal cavity: case report. Eur Arch
SC
Otorhinolaryngol. 2007;264:205-8.
18. Wu CJ, Wu PH, Chu ST, Yu WW, Chen PC. Features of a giant cell tumour of the parotid gland: A case report. Oncol Lett. 2013;6:829-832.
M AN U
19. Gulavani N, Selavraju K. Primary Soft Tissue Giant Cell Tumor Of Neck. WebmedCentral general surgery 2010;1(10):WMC00901
20. Callı AO, Tunakan M, Katilmiş H, Kilçiksiz S, Oztürkcan S. Soft tissue giant cell tumor of low malignant potential of the neck: a case report and review of the literature. Turk Patoloji Derg. 2014;30(1):73-77.
TE D
21. Goze OF, Muslehiddinoğlu A. Primary giant cell tumor of soft tissue on mandibular region:
AC C
EP
a case report and literature review. Basic Clin Sci 2013;2:71-82
RI PT
ACCEPTED MANUSCRIPT
LEGENDS:
SC
Figure 1: Histological image of lip giant cell tumor of soft tissue (EE 10 x) Figure 2: CD68 immunohistochemical staining of the lip giant cell tumor.
M AN U
Figure 3: CT-PET images of the gluteus localization of the giant cell tumor of soft tissue. Figure 4: Histological image of the giant cell tumor of soft tissue in correspondence of the gluteus
AC C
EP
TE D
(EE 10 x)
ACCEPTED MANUSCRIPT TABLE 1. Clinicopathologic features of giant cell tumours of soft tissues with a head and neck localization.
Year 1981
Age 75
Sex M
Location neck
Size 3 cm
Treatment Local excision
Grabellus et al3
2006
73
M
Temporal forehead
1 cm
surgically resected
Guccion and Enzinger11
1972
33
F
Right face
2.5 cm
Maheswaran 1990 and Addis12
92
F
cheek
2.7 cm
2002
73
M
forehead
1 cm
Lentini et al9
2010
79
F
Oliveira et al14 Pepper et al15
2000
9
M
Right paranasal region skin neck
2010
59
F
Torabinezad et al16 Tuluc et al17
2006
35
1.5 cm
Wide excision excision
na
na
na
masseter
2 cm
na
F
parotid
1.5 cm
Incomplete excision + adiuvant radiotherapy (45 Gy in 20 fractions) excision
na
Nasal cavity parotid
0.7 cm
excision
NED
4 cm
Incomplete excision + adiuvant radiotherapy (64 Gy in 32 fractions)
NED
EP
AC C
Wu et al 18
TE D
13
2007
32
F
2013
58
M
SC
M AN U
Hoang et al
Follow-Up Died after 1% years with multiple subcutaneous tumors and lung metastases two tumor relapses of the GCT-ST after 6 and 11 months. Alive 1 local recurrence. Alive No recurrence. NED Alive Lost to follow-up NED
RI PT
Author Angervall et al10
Radical excision
Wide excision
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT