Soft tissue sarcoma of the head and neck region in adults

Int. J. Oral Maxillofac. Surg. 2003; 32: 43–48 doi:10.1054/ijom.2001.0218, available online at http://www.sciencedirect.com

Clinical Paper Head and Neck Oncology

Soft tissue sarcoma of the head and neck region in adults M. Pandey, K. Chandramohan, G. Thomas, A. Mathew, P. Sebastian, T. Somanathan, E. K. Abraham, B. Rajan, M. Krishnan Nair: Soft tissue sarcoma of the head and neck region in adults. Int. J. Oral Maxillofac. Surg. 2003; 32: 43–48.  2002 Published by Elsevier Science Ltd on behalf of International Association of Oral and Maxillofacial Surgeons. Abstract. Soft tissue sarcomas (STS) are rare solid tumours accounting for less than 1% of all malignancies and are very unusual in the head and neck region. Histopathologically diagnosed cases of STS treated at Regional Cancer Centre (RCC), Trivandrum, India, between January 1989 and November 2000 were analyzed retrospectively. Survival analysis was carried out by Kaplan–Meier method and curves were compared using log rank test. A total of 22 cases were seen during the study period. The mean age of the patients was 36.4 years with male-to-female ratio of 2:1. The neck, lower jaw, tongue, cheek, scalp and maxilla were the commonest sites affected. None of the patients had palpable neck nodes or distant metastasis at presentation. All the patients were treated with primary surgical resection and this was followed by adjuvant treatment in 14 cases (63.6%). After a median follow-up of 14.5 months, two patients died, six developed local recurrence, four developed metastatic disease and another patient developed second primary sarcoma. The overall 5-year survival was 80% while the 5-year disease-free survival rate was 24.1%. The majority of the patients failed within first and second year. None of the parameters except grade of tumour (P=0.008) were found to have a significant effect on survival. The overall survival rate for patients with soft tissue sarcoma of the head and neck is good, however, disease-free survival is poor as the majority of these fail within 2 years of completing treatment.

Introduction Soft tissue sarcoma (STS) is a rare solid tumour that accounts for less than 1% of all malignancies among adults in the USA19. In India, the incidence ranges from 0.6 in Bangalore to 1.5 in New Delhi per 100 000 males and 0.3 in Bangalore to 1.7 in New Delhi per 100 000 females10,12. At the Regional Cancer Centre (RCC), Trivandrum, it constitutes about 1.4% and 0.8% of all malignancy among adult males and females respectively11. It mainly arises in the extremities and trunk and only 5–20% of all STSs arise 0901-5027/03/010043+06 $30.00/0

in the head and neck region13,18. It is still rare in the soft tisues of the oral cavity7,19. STSs have a varied cell of origin but are grouped together because of their similarities in clinical presentation, natural history, treatment and outcome. The most common STS occurring in the head and neck region is rhabdomyosarcoma (RMS), constituting 18%, followed by malignant fibrous histiocytoma (MFH), fibrosarcoma and neurofibrosarcoma18. A 45-year review of soft tissue sarcoma of the head and neck region from British Columbia found 139 cases of head and neck sarcoma constituting 1.24% of all

M. Pandey1, K. Chandramohan1, G. Thomas2, A. Mathew3, P. Sebastian1, T. Somanathan4, E. K. Abraham4, B. Rajan5, M. Krishnan Nair5 Divisions of 1Surgical Oncology, 2Community Oncology, 3Epidemiology, 4Pathology, and 5 Radiation Oncology, Regional Cancer Centre, Medical College, Thiruvananthapuram, Kerala, 695 011, India

Key words: sarcoma; soft tissue tumours; neurogenic neoplasm; vascular tumours; schwannoma; angiosarcoma; fibrous histiocytoma. Accepted for publication 23 December 2001

cases; only 16 (0.14%) of these were in intraoral sites5. Surgery is the primary modality of treatment. Radiotherapy is usually used as an adjuvant to achieve better local control, however, there are isolated case reports of use of radiotherapy as the primary modality1. The role of adjuvant chemotherapy is not clearly defined, as there are only a few randomized trials due to the low incidence of disease at these sites4. Furthermore, the head and neck region comprises many sub-sites and biologic behaviour of tumours may be different at these sub-sites. We carried

 2002 Published by Elsevier Science Ltd on behalf of International Association of Oral and Maxillofacial Surgeons.

42

54 33

53 35

30 36 22 40

15 16 34

17 56 68 73 28 15

54 15

52 13

1

2 3

4 5

6 7 8 9

10 11 12

13 14 15 16 17 18

19 20

21 22

M M

F M

M M M M F M

M F M

M M M M

F F

M F

F

Sex

Site

Face (NOS) Jaw

Face (NOS) Alv

Lip Neck Tongue Neck Maxilla Alveolus

Tongue Check Jaw

Neck Scalp Jaw Parotid region

Check Hypopharynx

Maxilla Scalp

Face (NOS)

Histopathology

Pleosarcoma MFH

Liposarcoma RMS

RMS Spindle cell Spindle cell Spindle cell Pleosarcoma Neurofibrosarcoma

Spindle cell Angiosarcoma Liposarcoma

Mal Sch MFH Spindle cell Mal Sch

Spindle cell Angiosarcoma

MFH RMS

Spindle cell

2 1

2 2

2 2 1 2 2 1

— 2 2

2 — 2 2

— —

2 —

2

T-stage

Grade

High Low

High High

High Intermediate Intermediate Intermediate High High

High Low Low

High — High High

Intermediate Low

Intermediate High

Intermediate

Surgery

Radical maxillectomy WE

Radical maxillectomy Alveolectomy

WE+HM+MND+PMMC WE WE WE+LD flap WE+radical maxillectomy WE+alveolectomy

WE+SOHND WE+HM+SHND WE

WE WE WE+HM+SHND WE+MM+MND+PMMC+DP

FTWE+Rhomboid flap WE

We+zygoma+part maxillectomy WE+STG+MND

WE+HM+PMMC

50/25 +

— 50/25

45/22 — — — — —

— ?/? ?/?

— — 55/25 ?/?

60/30 60/30

60/30 45/20

—

Adj RT dose/for

— +

Adr+C+Hol VCR+ActD

VAC — — — — —

VAC — —

— — — —

— —

— VAC

ADR

Adjuvant CT regimen

8 1

8 13

20 7 5 7 2 14

44 96 48

36 1 19 36

5 120

65 15

43

Total survival

6 1

6 6

9 7 5 7 2 6

44 96 26

36 1 14 24

5 9

58 0

43

Diseasefree survival

Outcome Base of skull Rec NED Progressive metastatic disease NED Presented with LR Salvaged by S+RT Presently NED NED LTF after surgery Expired Metastatic progressive disease NED NED Local rec salvaged by chemotherapy Expired lung mets NED/LFT Second primary NED NED/LTF Local rec Chemo/RT alive with Dis Local Rec+lung mets. Local Rec treated with chemo/NED at present Local Rec Disease free

Act D: actinomycin; Adj: adjuvant; ADR: adriamycin; DP: deltopectoral flap; FTWE: full-thickness wide excision; Hol: holoxon; HM: hemimandibulectomy; LD: lattismus dorsi; LTF: loss to follow-up; Mal: malignant; MFH: maligant fibrohistiocytoma; MM: marginal mandibulectomy; MND: modified neck dissection; NED: no evidence of disease; NOS: not otherwise specified; Pleo: pleomorphic; PMMC: pectoralis major myocutaneous flap; Rec: recurrence; RMS: rhabdomyosarcoma; Sch: schwannoma; SHND: suprahyoid neck dissection; mets-metastasis; SOHND: supraomohyoid neck dissection; STG: split thickness graft; VAC: vincristin, adriamycin, cyclophosphamide; WE: wide excision; part: partial; RT: radiotherapy; LR: local recurrence; CT: chemotherapy; C: cyclophosphamide; S: surgery; Dis: disease.

Age

Sl. No.

Table 1. Clinicopathological and treatment details in cases of soft tissue sarcoma

44 Pandey et al.

Head and neck sarcoma

45

out a retrospective analysis of adult patients with histologically proven STS of the head and neck region treated at RCC, Trivandrum, over a 12-year period (1989–2000).

Patients and methods The cases were extracted from the records of the Department of Surgical Oncology, RCC. Details of the clinical presentation, histology and the treatment were extracted from the case records. Histopathology slides were reviewed by the authors. All patients had undergone haematology and blood biochemistry tests and a chest roentgenogram on initial presentation as a routine procedure. Additional special investigations such as CT scanning, bone scans etc. were carried out as required. Survival analysis was carried out by Kaplan–Meier method and survival of different groups for variables such as duration of symptoms, tumour size and stage, grade, histopathology and adjuvant treatment was tested by log rank test.

Fig. 1. Clinical photograph showing an STS arising from the upper alveolus filling the buccogingival sulcus and protruding from the mouth.

Results Between January 1989 and November 2000, 22 cases of head and neck sarcoma were seen at the Surgical Oncology outpatient clinic. The mean age of the patients was 36.418.2 years, ranging from 13–73 years with a male to female ratio of 2:1. The most common sites were the neck, face (NOS) and lower jaw (three cases) followed by cheek, tongue, alveolus, scalp and maxilla in two patients each. Other sites were the hypopharynx, and parotid region in one patient each (Table 1, Figs 1 and 2). A progressive swelling or mass was the most common symptom, which was present in all cases. This was painful in three (13.6%) patients and painless in the rest. Facial nerve palsy was present in one case with a tumour of the parotid region and bleeding was present in another. The mean duration of symptoms was 10.4 months (range 1 month to 60 months). The average tumour size was 6.4 cm in its longest diameter and this ranged from 1–15 cm. The largest tumour was in the parotid region. It started as a small swelling, which was biopsied elsewhere and was reported as a malignant schwannoma. The tumour showed rapid growth after biopsy and

Fig. 2. Clinical photograph showing STS arising from the cheek and upper alveolus.

it reached 15 cm in size in less than 1 month (Table 1). Diagnosis The commonest histopathological type was RMS and MFH, seen in three cases each (13.6%). Malignant schwannoma, angiosarcoma, liposarcoma and pleomorphic sarcoma were present in two cases each (9.1%), and neurofibrosarcoma in one (4.5%) (Table 1). There were seven cases (31.8%) of spindle-cell sarcoma, in which further histological typing was not possible. Based on tumour size, 13 cases (59%) were T2 and four (18.2%) were in T1 stage. Ten cases (45.4%) had high-grade (G3) tumours, six (27.3%) had intermedi-

ate grade (G2) and five (22.7%) had low-grade (G1) tumours. In one case (4.5%) grading could not be carried out. None of the patients had palpable neck nodes or distant metastasis at the time of presentation. Treatment All patients were treated by surgery as a primary modality. Wide excision was carried out in all cases – this was full thickness in one case. This was combined with hemimandibulectomy in five cases (22.7%), maxillectomy in four (18.2%) alveolectomy in two (9.1%) and excision of zygoma in one case (4.5%). Neck dissection was performed in six cases (27.3%); procedures comprised

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Fig. 3. DFS (Kaplan–Meier) among patients with head and neck STS. Table 2. Overall and disease free survival (DFS) and factors influencing DFS in head and neck sarcoma and results of univariate analysis for various prognostic factors Variable Overall survival Disease-free survival Factors Age <35 years >35 years Duration of symptoms <3 months >3 months Grade of the tumour Low Intermediate High Sex Male Female Adjuvant treatment None Adjuvant Sites Intraoral Neck Craniomaxillofacial Histopathology Vascular Neural origin RMS SCS Others

No. of Mean Median 1-year 2-year 3-year patients survival† survival† survival‡ survival‡ survival‡ P-value 22 22

100 33

— 14

100 51.5

80 51.5

80 32.2

—

15 7

32 33

14 —

55.1 51.4

39.3 51.4

31.5 51.4

0.9

9 10

14 47

6 43

25.4 77.1

12.7 64.2

12.7 51.4

0.07*

4 6 10

44 43 16

26 43 9

66.6 83.3 40.4

66.6 83.3 20.2

33.3 83.3 20.2

0.008*

12 10

27 25

24 6

64.3 30

42.8 30

32.1 30

0.45

8 14

21 33

— 14

52.5 54.1

52.5 38.6

52.5 30.9

0.78

8 3 11

33 — 21

9 — 14

29.1 100 58.4

29.1 100 35

29.1 100 23.3

0.27

2 3 3 7 7

48 22 5 37 40

9 24 6 43 26

50.0 66.7 33.3 83.3 52.5

50.0 33.3 33.3 83.3 52.5

50.0 33.3 33.3 83.3 35

0.77

*Significant difference; †months; ‡percentage.

suprahyoid neck dissection in one case (4.5%) supraomohyoid neck dissection in two (9.1%) and modified neck dissection in three cases (13.6%). The modified neck dissection was carried out for those either with bulkydisease or to facilitate reconstruction by means of a pectoralis major flap, while supramohyoid dissection was carried out for cases where the clinically negative neck was entered for excision of a primary tumour (Table 1). The primary surgical excision was combined with reconstruction in six

cases (27%). The pectoralis major myocutaneous flap was used for reconstruction in three cases (13.6%); it was combined with a deltopectoral flap in one (4.5%). The lattisimus dorsi myocutaneous flap was used in one case (4.5%), while a rhomboid flap was used in another case (4.5%). The mandible was not reconstructed in any patient. While; the defect of the patients undergoing maxillectomy was skin grafted and an obturator prosthesis inserted in the post operative period undergoing maxillec-

tomy or who had a skin graft, or an obturator prosthesis inserted in the postoperative period. Adjuvant treatment was given in 14 cases (63.6%). Radiotherapy alone was given in seven cases (31.8%) and was combined with chemotherapy in four (18.2%). Chemotherapy alone was given to three patients (13.6%), while eight (36.4%) received no adjuvant treatment (Table 1). After a median follow-up of 14.5 months, nine patients (45.5%) are alive and are still disease-free. Six cases (27.3%) had local recurrences that was salvaged in two cases. Four (18.2%) had metastatic disease while one patient (4.5%) developed a secondary primary tumour. Two patients (4.5%) died during the follow-up; four cases with metastasis are alive with progressive disease, while three patients were lost to follow-up. The 5-year overall survival rate was 80%, whereas the 5-year disease-free survival (DFS) rate was 24.1% (Fig. 3). The majority of the failures occurred within the first (1-year DFS 51.5%) and second year (2-year DFS 38.6%) after treatment (Table 2). The survival rate was better among older patients (>35 years) compared to those younger than 35 years old (Table 2). DFS at 5 years was 51.4% for older patients and 21.0% for younger patients but the difference was not statistically significant (P=0.9). The duration of symptoms was found to have near significance on survival (P=0.07) (Fig. 4). The patients with a mean duration of symptoms to treatment of less than 3 months had a 5year survival rate of 12.7% compared to 34.2% among patients with symptom duration of more than 3 months (Table 2). Patients with smaller tumours had a better survival rate. Patients with tumours <5 cm had a 5-year DFS rate of 33.3%. None of the patients with tumours larger than 5 cm survived for more than 43 months; the difference in survival was however not statistically significant (P=0.79) (Fig. 5). The grade was found to have a statistically significant effect on survival (P=0.008). Patients with grade 3 tumours had a 5-year DFS rate of 18.3%; patients with grade 2 tumours had a 41.7% 5-year DFS, and in those with grade 1 tumours there was a 50% 5-year DFS rate (Table 3, Fig. 6). The site of origin of the tumour was found to have no statistically significant effect upon survival (P=0.27).

Head and neck sarcoma

47

Males were found to have a 5-year DFS rate of 34.9%, while it was 15% in females; the differences was not statistically significant (P=0.33). Those with tumours of neural origin were found to have a 5-year DFS of 33.33%, while all patients with vascular sarcomas and RMS failed, the difference in survival between various histopathological types was not statistically significant (P=0.27).

Discussion

Fig. 4. DFS by duration of symptoms in head and neck sarcoma.

Fig. 5. DFS by size of tumour in patients with sarcoma of the head and neck region.

Fig. 6. DFS by grade of tumour in patients with sarcoma of the head and neck region.

STSs arising in the head and neck region account for about <5% of all sarcomas. STS comprises a group of relatively rare but anatomically and histologically diverse neoplasms despite having a common embryonic origin, arising from tissues derived from the mesoderm. STS usually occurs in all age groups and shows a bimodal age distribution. Sarcomas in the head and neck region are more common among children and young adults. E et al.2 found the median age to be 32 years; 53% of their patients were males. In the present series, the mean age was almost similar with a higher incidence among males. A progressive mass lesion was the commonest presenting symptom in our series and was associated with pain in 20% of cases. The incidence of pain in one series reported earlier was up to 33%5,13. One patient with a large tumour in the parotid region presented with facial nerve palsy and another patient with extensive maxillary STS presented with intractable bleeding following biopsy. In contrast to earlier reports of lymphadenopathy in up to 15% of cases15, in the present series lymphadenopathy was absent in all cases. The patients who underwent neck dissections were found to have pathologically negative nodes. T et al.17 reporting on 164 cases of adult STS of the head and neck found angiosarcoma to be the most common histopathological type (15.8%), followed by fibrosarcoma (12%) and unclassified sarcomas (11%) in cases. Similarly in the series of G et al.6 fibrosarcoma was the commonest tumour in 26.5% followed by malignant schwannoma in 15%. In the present series, the commonest pathological type was unclassified spindle-cell sarcoma present in 31.8% of the patients followed by malignant fibrous histiocytoma, and RMS (13.6%). The large numbers of unclassified sarcomas (spindle cell and pleomorphic) in this series are due to a lack of

48

Pandey et al.

immunohistochemistry for the majority of the earlier cases. In the present series, all patients were treated by surgery as a primary modality of treatment with or without adjuvant radiotherapy, chemotherapy or both. This is in contrast to an earlier reported series2,5,6,9,17, where a small percentage of patients were treated with radiotherapy alone or in combination with chemotherapy. However, in all studies there is consensus that surgery is the primary modality of choice. The role of radiotherapy is mostly adjuvant2,16. However, a small percentage of patients have been treated with radiotherapy as the primary modality with or without chemotherapy6,9,17. The role of chemotherapy is purely adjuvant either in combination with surgery or radiotherapy or both16. G et al.4 in a randomized prospective trial on adjuvant chemotherapy found a statistically significant tendency towards improved DFS among patients treated with chemotherapy (P=0.018) but there was no statistically significant improvement in overall survival (P=0.46)4. The 5-year survival rate in head and neck sarcoma is reported to range between 20–80% in various studies3,4,8. The 5-year overall survival rate in the present series too was high at 80%, but the DFS at 5 years was 24.1%. Earlier studies reporting on prognostic factors have found that site of origin, histological type, grade of the tumour, tumour depth, compartmental status, age, tumour size, tumour margins, quality of excision, presence of necrosis, mitotic count and blood vessel invasion have a significant effect on prognosis2,3,9,17. In contrast, in our study, analysis showed only the grade and duration of symptoms to have a prognostic importance. This may be due to the small number of participants and absence of complete information on all cases, this being a retrospective analysis.

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Address: Dr Manoj Pandey Assistant Professor, Surgical Oncology Regional Cancer Centre Medical College PO Thiruvananthapuram Kerala, 695 001, India Tel: +91 471 442541/443667 Fax: +91 471 447454 E-mail: [email protected]; [email protected]