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Spindle cell carcinoma: the general demographics, basic clinico-pathologic characteristics, treatment, outcome and prognostic factors

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Oncotarget. 2017; 8:43228-43236. https://doi.org/10.18632/oncotarget.18017

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Lei Feng, Deng Cai, Alanuer Muhetaer, Yin-Long Yang, Fei Ren, Mumingjiang Yishake, Hao Zhang, Yuan Fang and Alimujiang Wushou _

Abstract

Lei Feng1, Deng Cai2, Alanuer Muhetaer3, Yin-Long Yang4, Fei Ren5, Mumingjiang Yishake6, Hao Zhang7, Yuan Fang8 and Alimujiang Wushou1

1Department of Oral and Maxillofacial Surgery, Shanghai Stomatological Hospital, Fudan University, Shanghai 200001, China

2Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China

3Department of Gynaecology, Zhongshan Hospital, Fudan University, Shanghai 200000, China

4Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China

5Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China

6Department of Orthopedics Surgery, Zhongshan Hospital, Fudan University, Shanghai 200000, China

7Department of Epidemiology and Biostatistics, Shanghai Stomatological Hospital, Fudan University, Shanghai 200001, China

8Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200000, China

Correspondence to:

Alimujiang Wushou, email: wushoua@fudan.edu.cn

Keywords: spindle cell carcinoma, SEER analysis, prognostic factors

Received: February 20, 2017     Accepted: April 17, 2017     Published: May 19, 2017

ABSTRACT

Background: Owing to the rarity, the general demographics, basic clinico-pathologic features, management, outcome and prognostic factors of spindle cell carcinoma (SpCC) were unexplored. Methods: A SEER analysis was performed with 2336 cases (1973-2016). Results: A peak incidence occurred at 70~80 years without any gender predominance and 83.13% occurred in white people. The respiratory system was mostly affected tumor site (35%). Significant overall survival (OS) and disease specific survival (DSS) were found differentiated in gender, age, marital status, primary tumor location, AJCC stage, T stage, N stage, M stage, pathologic grade and treatment modality. In the multivariate Cox model, the age > 69 years (Hazard ratio [HR] = 1.427 for OS, P = 0.01 and HR = 1.491 for DSS, P = 0.003; Reference [Ref] age ≤ 69 years), tumor location in respiratory system (HR = 1.550 for OS, P = 0.041 and HR = 1.561 for DSS, P = 0.04; Ref: digestive system), N2 stage (HR = 1.962 for OS, P = 0.006 and HR = 1.982 for DSS, P = 0.004; Ref: N0 stage) and AJCC stage IV (HR = 4.601 for OS, P = 0.000 and HR = 5.107 for DSS, P = 0.000; Ref: stage I) were independently associated with worse OS and DSS. Conclusions: SpCC mostly occurred in white people at 70~80 years old without predominance in any gender. The respiratory system was mostly affected site. The patient’s age, primary tumor location, AJCC stage were independent prognostic indicators for both DSS and OS of SpCC.


Spindle cell carcinoma: the general demographics, basic clinico-pathologic characteristics, treatment, outcome and prognostic factors | Feng | Oncotarget

INTRODUCTION

Spindle cell carcinoma (SpCC), also called sarcomatoid carcinoma, is a relatively uncommon and it has histologic, cytologic and molecular properties of both epithelial and mesenchymal tumors [1, 2]. Thus, it presents heterogeneous pathologic features, clinical behavior and prognosis [35]. In the past, it was easily be misdiagnosed because of the unfamiliarity. Nowadays, sophisticated pathologic molecular techniques has made the diagnosis of SpCC reliable [6].

For SpCC, there is no standard treatment protocol available from previously published studies. Treatment modalities of SpCC has varied across previous reports [7, 8]. Although the mainstay treatment for SpCC is surgery, it varied from local excision to radical surgery [5, 7, 9]. The addition of radiotherapy or chemotherapy to treatment protocol has also varied. In most cases, radiotherapy and chemotherapy were added after surgery considering various common cancer adverse prognostic factors such as unconfirmed surgical margins, poor pathologic differentiation and advanced tumor stage etc [8, 1012].

Regarding general demographics, basic clinico-pathologic features, management strategies and prognosis, there is lack of instructive data to guide SpCC management and to evaluate prognosis, owing to the rarity of the disease. We assume that a nationwide population-based cohort may provide an opportunity to evaluate trends in overall demographic features, basic clinico-pathologic characteristics and compare treatment modalities and outcome of SpCC. Thus, we performed a generalized investigation of all SpCC cases registered in the Surveillance, Epidemiology, and End Results (SEER) from 1973 to 2016.

RESULTS

A total of 2336 cases with diagnosis of SpCC were found in the SEER database from 1973 to 2016. The median follow-up time was 32.5 months (range, 1-437 months). Gender distribution was nearly equal including 1191 men and 1145 women. Majority of SpCC occurred in white people (83.13%, 1942/2336). A peak incidence occurred during the seventh decade of life. SpCC could be found in almost any site of the body. However, one third of SpCC originated from respiratory system. The age and site distribution are shown in Figure 1. The basic demographic and clinico-pathologic characteristics of the whole cases are summarized in Table 1.

Figure 1:

Figure 1: The distribution of age (A) and primary tumor location (B) of all SpCC cases registered in the SEER database.

Table 1: The basic demographic and clinico-pathologic characteristics of SpCC patients

Demographic and clinico-pathologic parameters

Disease specific survival

Overall survival

Alive

Dead

Total

P-value

Alive

Dead

Total

P-value

Gender

Female

216

666

882

0.005

271

874

1145

0.001

Male

173

738

911

213

978

1191

Age

≤ 69 years

271

661

932

0.000

318

794

112

0.000

> 69 years

118

743

861

166

1058

1224

Race

White

307

1156

1463

0.027

390

1552

1542

0.095

Black

41

153

194

48

190

238

Others

42

94

136

46

110

156

Tumor
location

Digestive system

152

361

513

0.000

110

231

331

0.000

Respiratory system

105

729

834

94

590

684

Endocrine system

15

131

146

10

105

115

Reproductive system

125

184

1969

100

161

261

Urinary system

30

131

161

28

80

108

Other site

16

22

38

6

11

17

Unknown

41

294

335

41

226

267

T stage

TX+ T0

42

244

286

0.000

54

312

366

0.000

T1

104

72

176

135

105

240

T2

81

192

273

100

265

365

T3

41

135

176

50

163

213

T4

26

213

239

34

288

322

N stage

NX+N0

262

596

858

0.000

335

802

1137

0.000

N1

17

80

97

20

109

129

N2

13

152

165

15

188

203

N3

2

29

31

3

35

38

M stage

MX

13

48

61

0.000

18

75

93

0.000

M0

264

462

726

335

620

955

M1

17

347

364

20

437

457

AJCC stage

I stage

119

96

215

0.000

137

86

223

0.000

II stage

73

103

176

96

130

226

III stage

37

157

194

30

108

138

IV stage

25

263

288

33

349

382

SEER historic stage

Localized

233

265

498

0.000

289

380

669

0.000

Regional

73

229

302

83

418

501

Distant metastasized

24

494

518

31

636

667

Pathologic grade

Grade I

22

11

33

0.000

27

18

45

0.000

Grade II

23

27

50

34

34

68

Grade III

82

367

449

99

479

578

Grade IV

40

224

264

51

278

329

Treatment

Surgery alone

209

343

552

0.000

262

488

750

0.000

Radiotherapy

34

302

336

44

375

419

Surgery with radiotherapy

83

215

298

98

263

361

Kaplan-Meier analysis was performed for time-to-event analysis for OS. Significant OS differences were identified depending on gender (P = 0.000), age (P = 0.000), marital status (P = 0.005), tumor site (P = 0.000), AJCC stage (P = 0.000), T stage (P = 0.000), N stage (P = 0.000), M stage (P = 0.000), pathologic grade (P = 0.000) and treatment modality (P = 0.000) (Figure 2). Univariate and multivariate survival analysis using the cox proportional hazards regression model were performed. In the univariate analysis, gender, age, marital status, primary tumor site, AJCC stage, T stage, N stage, M stage, pathologic grade and treatment modality were associated with OS. Details of these analysis are shown in Table 2. More importantly, the age > 69 years [HR 95% CI: 1.427 (1.090-1.868), P = 0.01, age ≤ 69 years - as Ref], tumor location in respiratory system [HR 95% CI: 1.550 (1.001-2.400), P = 0.04, digestive system - as Ref], N2 stage [HR 95% CI: 1.962 (1.209-3.181), P = 0.006, stage N0 - as Ref], AJCC stage III [HR 95% CI: 2.242 (1.106-4.545), P = 0.025, stage I - as Ref] and AJCC stage IV [HR 95% CI: 4.601 (2.084-10.160), P = 0.000, stage I - as Ref] were independently associated with worse OS (Table 3).

Figure 2:

Figure 2: OS curves of cases with SpCC compared according to (A) gender, (B) age, (C) marital status, (D) tumor location, (E) AJCC stage, (F) T stage, (G) N stage, (H) M stage, (I) pathologic grade and (J) treatment modalities. Log-rank test was utilized to compare curves, and significance is presented on each panel.

Table 2: Univariate Cox regression analysis of characteristics associated with disease specific survival and overall survival

Parameters

Disease specific survival

Overall survival

HR (95% CI)

P-value

HR (95% CI)

P-value

Gender

Male

1.00 Reference

0.003

1.00 Reference

0.000

Female

0.854 (0.768-0.948)

0.841 (0.767-0.921)

Age

≤ 69 years

1.00 Reference

0.000

1.00 Reference

 

> 69 years

1.618 (1.455-1.800)

1.605 (1.462-1.763)

0.000

Marital status

Other status

1.00 Reference

 

1.00 Reference

 

Married

0.877 (0.790-0.975)

0.015

0.880 (0.803-0.965)

0.006

Tumor
location

Digestive system

1.00 Reference

 

1.00 Reference

 

Endocrine system

2.365 (1.874-2.984)

0.000

2.150 (1.758-2.630)

0.000

Reproductive system

0.791 (0.646-0.967)

0.022

0.716 (0.599-0.855)

0.000

Respiratory system

1.951 (1.673-2.276)

0.000

2.024 (1.781-2.300)

0.000

Urinary system

1.384 (1.071-1.789)

0.013

1.525 (1.247-1.864)

0.000

AJCC stage

Stage I

1.00 Reference

 

1.00 Reference

 

Stage II

1.418 (1.075-1.871)

0.014

1.414 (1.087-1.841)

0.010

Stage III

3.266 (2.526-4.223)

0.000

3.511 (2.662-4.632)

0.000

Stage IV

6.904 (5.406-8.818)

0.000

7.026(5.556-8.884)

0.000

T stage

T1

1.00 Reference

 

1.00 Reference

 

T2

2.014 (1.536-2.642)

0.000

1.951 (1.555-2.446)

0.000

T3

3.036 (2.296-4.085)

0.000

2.950 (2.305-3.776)

0.000

T4

5.337 (4.062-7.014)

0.000

5.014 (3.990-6.302)

0.000

N stage

N0

1.00 Reference

 

1.00 Reference

 

N1

1.472 (1.163-1.863)

0.001

1.485 (1.215-1.816)

0.000

N2

2.525(2.104-3.030)

0.000

2.424 (2.061-2.850)

0.000

N3

2.972 (2.039-4.331)

0.000

2.892 (2.055-4.070)

0.000

M stage

MX

1.00 Reference

 

1.00 Reference

 

M0

0.649 (0.482-0.875)

0.004

0.591 (0.465-0.752)

0.000

M1

2.730 (2.011-3.706)

0.000

2.356 (1.840-3.018)

0.000

Pathologic grade

G1

1.00 Reference

 

1.00 Reference

 

G2

1.620 (0.804-3.268)

0.177

1.220 (0.689-2.161)

0.0495

G3

3.823 (2.097-6.968)

0.000

3.164 (1.975-5.068

0.000

G4

4.092 (2.232-7.502)

0.000

3.367 (2.089-5.428)

0.000

Treatment

Surgery alone

1.00 Reference

 

1.00 Reference

 

Radiotherapy alone

2.814 (2.402-3.296)

0.000

2.725 (2.374-3.128)

0.000

Surgery + radiotherapy

1.300 (1.095-1.542

0.000

1.236 (1.064-1.436)

0.006

Table 3: Multivariate Cox regression analysis of characteristics associated with disease specific survival and overall survival

Parameters

Disease specific survival

Overall survival

HR (95% CI)

P-value

HR (95% CI)

P-value

Age

≤ 69 years

1.00 Reference

 

1.00 Reference

 

> 69 years

1.491 (1.149-1.935)

0.003

1.427 (1.090-1.868)

0.010

Tumor location

Digestive system

1.00 Reference

 

1.00 Reference

 

Respiratory system

1.561 (1.009-2.415)

0.040

1.550 (1.001-2.400)

0.041

AJCC stage

Stage I

1.00 Reference

 

1.00 Reference

 

Stage III

-

 

2.242 (1.106-4.545)

0.025

Stage IV

5.107 (2.563-10.173)

0.000

4.601 (2.084-10.160)

0.000

N stage

N0

1.00 Reference

 

1.00 Reference

 

N2

1.982 (1.241-3.165)

0.004

1.962 (1.209-3.181)

0.006

There were 1793 cases available for diseases specific survival (DSS) analysis in the total cases. The median follow-up time was 34.2 months (range, 1-381 months) for these cases. Nearly two fifths of cases occurred in the respiratory system (38.2%, 685/1793). The median age was 69 years and cases with age ≤ 69 years account for 52%. The early AJCC stage cases (stage I + II) were 391 and advanced stage (stage III + IV) cases 482. Most of the cases were pathologically poorly differentiated or undifferentiated carcinoma. Nearly one third of the cases were treated by surgery alone. The detailed demographic and clinico-pathologic characteristics of SpCC cases with DSS status are presented in the Table 1.

The DSS analysis was performed as OS was done. Significant DSS differences were found depending on gender (P = 0.002), age (P = 0.000), marital status (P = 0.0126), primary tumor site (P = 0.000), AJCC stage (P = 0.000), T stage (P = 0.000), N stage (P = 0.000), M stage (P = 0.000), pathologic grade (P = 0.000) and treatment (P = 0.000) (Figure 3). In the univariate Cox regression model, gender, age, marital status, primary tumor site, AJCC stage, T stage, N stage, M stage, pathologic grade and treatment modality were correlated with DSS (Table 2). In the multivariate analysis, age [P = 0.003, HR 95% CI: 1.491 (1.149-1.935) for > 69 years; ≤ 69 years - as Ref], tumor location [P = 0.04, HR 95% CI: 1.561 (1.009-2.415) for respiratory system; digestive system - as Ref], N stage [P = 0.004, HR 95% CI: 1.982 (1.241-3.165) for N2 stage; N0 stage - as Ref] and AJCC stage [P = 0.000, HR 95% CI: 5.107 (2.563-10.173) for stage IV; stage I - as Ref] were independent prognostic parameters for DSS. Details of the multivariate Cox proportional hazards regression analysis are shown in Table 3.

Figure 3:

Figure 3: DSS curves of cases with SpCC compared according to (A) gender, (B) age, (C) marital status, (D) tumor location, (E) AJCC stage, (F) T stage, (G) N stage, (H) M stage, (I) pathologic grade and (J) treatment modalities. Log-rank test was utilized to compare curves, and significance is presented on each panel.

DISCUSSION

Except for sporadic case reports and small retrospective case series, there is no adequate data to describe SpCC demographics [13]. Current study results demonstrate a peak incidence of SpCC in the seventh decades of life and the male-to-female ratio is almost 1:1 without predominance in any gender. The typical incidence of SpCC was from fifth to seventh decades in majority of the previous reports [35]. The most studies about SpCC are based on single-center experience and their study population is less than fifty cases. Because of the small sample size, those studies are often not sufficiently powerful to find considerable differences in survival analysis regarding to general demographic parameter such as age, gender, etc. In this survival analysis, remarkable differences were identified in both age and gender regarding DSS and OS (Figures 2A, 2B, 3A and 3B). One of the most important findings in SpCC demographics is that age is an independent prognostic indicator for DSS and OS.

More than one thousand reports are available about SpCC with variety of tumor location in the PubMed to date. Well consisted with previous reports, SpCC almost occur at any site of the body in present investigation. For better characterization, the tumor locations were categorized into five groups according to the distribution of primary tumor site: (a) respiratory system, (b) digestive system, (c) endocrine system, (d) reproductive system and (e) urinary system. In the survival comparison of these five groups, significant survival differences were found in both DSS and OS (Figures 2D and 3D). The endocrine system, respiratory system and urinary system were unfavorably associated with DSS and OS of SpCC patients (Digestive system - as a ref) in univariate Cox model. Furthermore, the respiratory system (Digestive system - as a ref) was another adverse independent prognostic indicator not only for DSS but also for OS.

Much like other carcinomas, the AJCC staging of SpCC is a valuable tool for physicians in treatment planning and prognosis evaluation [14]. The AJCC staging data of SpCC was incomplete and two thirds of them were missing in the SEER database. Survival analysis was performed with available data. There were typical survival differences in T stage, N stage, M stage and AJCC stage (Figures 2 and 3). Among them, only N stage and AJCC stage were independent prognostic parameters for DSS and OS of SpCC (Table 3).

It has been widely investigated and recognized that SpCC has worse prognosis than SCC [15]. Intrinsic tumor properties and lack of standard treatment guidelines may be the possible explanations for the unfavorable prognosis. However, SpCC showed site specific prognosis [1618]. In this study we compared obtainable treatment modalities (Figures 2J and 3J). The results demonstrate that the surgery alone group had better DSS and OS than radiotherapy alone and surgery combined with radiotherapy group. Although this is not a standardized treatment comparison, it likely indicates that radiotherapy alone is the least option for SpCC treatment. Besides, it is difficult to draw firm conclusion that SpCC patients cannot benefit from radiotherapy according to the results in this study because there were many other confounding factors, such as unclear surgical margin, advanced tumor stage, pathologic grade, etc. Therefore, it is urgently necessary to reassess the effectiveness of radiotherapy for SpCC with multi-center well-controlled studies.

A few limitations of SEER registry and current investigation itself should be acknowledged. Firstly, not all cases have complete information, data on important parameters such as treatment modalities, pathologic grade and TNM/AJCC stage are incomplete. Secondly, due to the lack of chemotherapy data, the role of chemotherapy for SpCC could not be established. Thirdly, the median follow-up time was 32.5 months for OS and 34.2 months for DSS. The relatively short follow up time may not reveal longterm survival differences. Lastly, the retrospective nature of current investigation may have introduced bias into the overall analysis.

In conclusion, the main interest of this study is to give audience concise and generalized information about SpCC. Thus, we did not demonstrate many possible subgroup analysis and develop detailed discussions. Although SEER database are capable of providing the largest data about SpCC, those available date is still incomplete. Despite the limitation of the incomplete data and study itself, the present investigation is the first of its kind with the largest study population from multiple centers to define the overall demographic trends, basic clinico-pathologic characteristic, management and prognosis of SpCC. The investigation results demonstrate that SpCC mostly occurred at 70~80 years old in white people and sex distribution was almost equal. The patient’s age, primary tumor location, N stage and AJCC stage were independent prognostic indicators for both DSS and OS.

MATERIALS AND METHODS

International Classification of Diseases for Oncology codes (ICD-O-3) for spindle cell carcinoma (8032/3) was used for identification of cases with a diagnosis of SpCC registered in the SEER database and SEER*Stat software, version 8.3.2, was applied for data extraction.

For statistical analysis, the following demographic and clinico-pathologic parameters were selected: age, gender, race, marital status, primary tumor site, American joint committee on cancer (AJCC) stage, pathologic grade, treatment modality, follow-up time and outcome status. Not all of the cases that we identified contained all these data. Statistical analysis was performed by using the software of the Statistical Package for Social Sciences, version 23.0, for Windows (SPSS, Chicago, IL). Differences in the numerical parameters were evaluated by using the Student’s test or non-parametric Wilcoxon test and the chi square test or Fisher exact test was used for categorical variables comparison. The survival curves were generated by using the Kaplan-Meier method, and the log-rank test was performed to evaluate the survival difference. Adjusted hazard ratios (HRs) along with 95% confidence intervals (CIs) were calculated by using the Cox proportional hazards regression model. When the P-value was < 0.05, the difference was regarded as statistically significant. All statistical tests were two tailed.

ACKNOWLEDGMENTS

We are grateful to Dr. Kamila Abulimiti (MD) from Strayer University (USA) for checking the English of the manuscript.

CONFLICTS OF INTEREST

The authors declare no conflicts of interest.

FUNDING

This study was supported by The Scientific Research Foundation of Shanghai Stomatological Hospital, Fudan University (SSDCZ-2016-01).

REFERENCES

1. Battifora H. Spindle cell carcinoma: ultrastructural evidence of squamous origin and collagen production by the tumor cells. Cancer. 1976; 37:2275-2282.

2. Gupta R, Singh S, Hedau S, Nigam S, Das BC, Singh I, Mandal AK. Spindle cell carcinoma of head and neck: an immunohistochemical and molecular approach to its pathogenesis. J Clin Pathol. 2007; 60:472-475.

3. Ung M, Rouquette I, Filleron T, Taillandy K, Brouchet L, Bennouna J, Delord JP, Milia J, Mazières J. Characteristics and clinical outcomes of sarcomatoid carcinoma of the lung. Clin Lung Cancer. 2016; 17:391-397.

4. Malla M, Wang JF, Trepeta R, Feng A, Wang J. Sarcomatoid carcinoma of the urinary bladder. Clin Genitourin Cancer. 2016; 14:366-372.

5. Chang NJ, Kao DS, Lee LY, Chang JW, Hou MM, Lam WL, Cheng MH. Sarcomatoid carcinoma in head and neck: a review of 30 years of experience—clinical outcomes and reconstructive results. Ann Plast Surg. 2013; 71:S1-S7.

6. Lee AH. Recent developments in the histological diagnosis of spindle cell carcinoma, fibromatosis and phyllodes tumour of the breast. Histopathology. 2008; 52:45-57.

7. Ellis GL, Corio RL. Spindle cell carcinoma of the oral cavity. A clinicopathologic assessment of fifty-nine cases. Oral Surg Oral Med Oral Pathol. 1980; 50:523-33.

8. Olsen KD, Lewis JE, Suman VJ. Spindle cell carcinoma of the larynx and hypopharynx. Otolaryngol Head Neck Surg. 1997; 116:47-52.

9. Viswanathan S, Rahman K, Pallavi S, Sachin J, Patil A, Chaturvedi P, D’Cruz A, Agarwal J, Kane S. Sarcomatoid (spindle cell) carcinoma of the head and neck mucosal region: a clinicopathologic review of 103 cases from a tertiary referral cancer centre. Head Neck Pathol. 2010; 4:265-275.

10. Kim JH, Leeper RD. Treatment of anaplastic giant and spindle cell carcinoma of the thyroid gland with combination Adriamycin and radiation therapy. A new approach. Cancer. 1983; 52:954-957.

11. Sneige N, Yaziji H, Mandavilli SR, Perez ER, Ordonez NG, Gown AM, Ayala A. Low-grade (fibromatosis-like) spindle cell carcinoma of the breast. Am J Surg Pathol. 2001; 25:1009-1016.

12. Mainwaring MG, Poor C, Zander DS, Harman E. Complete remission of pulmonary spindle cell carcinoma after treatment with oral germanium sesquioxide. Chest. 2000; 117:591-593.

13. Bigby SM, Eva LJ, Jones RW. Spindle cell carcinoma of the vulva: a series of 4 cases and review of the literature. Int J Gynecol Pathol. 2014; 33:203-212.

14. Marrelli D, Morgagni P, De MG, Coniglio A, Marchet A, Saragoni L, Tiberio G, Roviello F. Prognostic value of the 7th AJCC/UICC TNM classification of noncardia gastric cancer: analysis of a large series from specialized Western centers. Ann Surg. 2012; 255:486-491.

15. Bice TC, Tran V, Merkley MA, Newlands SD, van der Sloot PG, Wu S, Miller MC. Disease-specific survival with spindle cell carcinoma of the head and neck. Otolaryngol Head Neck Surg. 2015; 153:973-980.

16. Gerry D, Fritsch VA, Lentsch EJ. Spindle cell carcinoma of the upper aerodigestive tract: an analysis of 341 cases with comparison to conventional squamous cell carcinoma. Ann Otol Rhinol Laryngol. 2014; 123:576-583.

17. Dubal PM, Marchiano E, Kam D, Dutta R, Kalyoussef E, Baredes S, Eloy JA. Laryngeal spindle cell carcinoma: a population-based analysis of incidence and survival. Laryngoscope. 2015; 125:2709-2714.

18. Moten AS, Jayarajan SN, Willis AI. Spindle cell carcinoma of the breast: a comprehensive analysis. Am J Surg. 2016; 211:716-721.


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