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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 4  |  Issue : 3  |  Page : 466-471

Clinical presentation and pattern of care for sarcomatoid variant of squamous cell carcinoma of the head-and-neck region: A retrospective study


1 Department of ENT, BARC Hospital, Mumbai, Maharashtra, India
2 Department of Surgical Oncology, Division of Head and Neck Oncology, Tata Memorial Center, Mumbai, Maharashtra, India
3 Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India

Date of Submission24-Jun-2021
Date of Decision07-Aug-2021
Date of Acceptance16-Sep-2021
Date of Web Publication08-Oct-2021

Correspondence Address:
Shivakumar Thiagarajan
Department of Surgical Oncology, Division of Head and Neck Oncology, Tata Memorial Center, Parel, Mumbai - 400 012, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/crst.crst_148_21

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  Abstract 


Background: The sarcomatoid variant of squamous cell carcinoma (SCC) is an uncommon variant of head-and-neck cancer with a clinically aggressive course and poor outcomes. The data on the clinical presentation and pattern of treatment received by patients with sarcomatoid variant of SCC are scarce.
Objectives: In this study, we aimed to assess the clinical presentation, intent of treatment, and the subsequent treatment-related outcomes of patients with sarcomatoid variant of SCC of the head-and-neck region.
Materials and Methods: This retrospective study was conducted among treatment-naïve patients with sarcomatoid variant of SCC of the head-and-neck region who presented to the Tata Memorial Center, a tertiary care center, in Mumbai, India, between January 2012 and December 2018. The primary objective was to evaluate the stage at presentation and the intent of treatment received. The secondary outcome was disease-free survival (DFS). Variables were analyzed using simple descriptive statistical methods. DFS was calculated using the Kaplan–Meier method.
Results: A total of 60 patients with sarcomatoid variant of SCC were included in the study. The median age of the patients was 51 years, with a male-to-female ratio of 5:1. The oral cavity was the most common subsite, reported in 39 (65%) patients. A total of 43 (71.6%) patients presented with advanced-stage disease, and 41 (68.3%) received curative-intent treatment. The DFS of patients who received curative treatment was 76.3 months (95% confidence interval [CI], 60.3–92.4) and that of patients who received palliative-intent treatment was 11.6 months (95% CI, 9.2–14).
Conclusions: Sarcomatoid variant of SCC of the head-and-neck region usually presents with advanced-stage disease, however, has a reasonable DFS when treated appropriately with curative intent.

Keywords: Head and neck, sarcomatoid variant, squamous cell carcinoma, HNSCC, HNC


How to cite this article:
Chakraborthy A, Thiagarajan S, Bal M, Chaukar D. Clinical presentation and pattern of care for sarcomatoid variant of squamous cell carcinoma of the head-and-neck region: A retrospective study. Cancer Res Stat Treat 2021;4:466-71

How to cite this URL:
Chakraborthy A, Thiagarajan S, Bal M, Chaukar D. Clinical presentation and pattern of care for sarcomatoid variant of squamous cell carcinoma of the head-and-neck region: A retrospective study. Cancer Res Stat Treat [serial online] 2021 [cited 2021 Dec 9];4:466-71. Available from: https://www.crstonline.com/text.asp?2021/4/3/466/327760




  Introduction Top


Squamous cell carcinoma (SCC) is the most common histopathological subtype of cancers affecting the upper aerodigestive tract. It has many histopathological variants, the sarcomatoid variant being one among them.[1],[2] The sarcomatoid variant is uncommon and comprises only about 3% of all SCCs. The sarcomatoid variant of SCC is considered to be poorly differentiated and has an unfavorable prognosis.[1],[2] Sarcomatoid carcinoma is a biphasic tumor consisting of both epithelial and spindle cell components, which could be one of the reasons for its diverse nomenclature. Since its initial description in 1864,[3] various terms have been used to describe this malignancy, including spindle cell carcinoma, pseudosarcoma, carcinosarcoma, and pleomorphic carcinoma.[2] Sarcomatoid variant of SCC usually presents as a fleshy polypoidal growth in the upper aerodigestive tract, with the larynx being the most commonly reported site in the literature, followed by the oral cavity and hypopharynx.[4],[5],[6] It can also develop at other sites in the upper aerodigestive tract such as the paranasal sinuses and oropharynx.[7] These tumors usually present in the seventh decade of life, and men are affected more frequently compared to women.[7] Patients are known to present with a short history and an aggressive disease course with a tendency recur locally.[1],[5] The treatment of the sarcomatoid variant of SCC is usually dictated by the anatomic site and stage of the disease. However, surgery followed by adjuvant radiotherapy appears to provide good outcomes.[8] There are limited data in the literature regarding the presentation and management of patients with sarcomatoid variants of SCC. Therefore, in this study, we assessed the clinical presentation and the intent/pattern of treatment of patients diagnosed with the sarcomatoid variant of SCC of the head-and-neck, along with their outcomes, pattern of recurrence, and further treatment.


  Materials and Methods Top


General study details

This was a single-center retrospective study of patients with a histopathological diagnosis of sarcomatoid variant of SCC of the head-and-neck region treated at the Tata Memorial Center, a tertiary cancer center, in Mumbai, India. The study included patients treated in the Department of Head and Neck Surgical Oncology between January 1, 2012, and December 31, 2018. The study was conducted in accordance with the Declaration of Helsinki as revised in 2013 and adhered to the existing ethical standards. All patients received the standard of care for their condition and provided consent for the treatment that they received. No funding was obtained for this study.

Participants

Patients diagnosed with sarcomatoid carcinoma, spindle cell carcinoma, carcinoma with sarcomatoid features, or carcinosarcoma of any site in the upper aerodigestive tract and head-and-neck region, who received either curative or palliative treatment at our institute for their cancer were included in the study. Patients who had received any prior treatment (surgery, neoadjuvant treatment) and those who had recurrent/second primary cancers were excluded from the study. Patients who presented with recurrent tumors and tumors of different pathologies as well as those with incomplete records were also excluded from the study.

Variables

The primary outcomes of the study were the stage at presentation (early vs. advanced) and intent of treatment received (curative vs. palliative). The secondary outcome was disease-free survival (DFS) in patients who received curative-intent treatment.

Study methodology

We searched the information and technology server of our institution using the following search terms: sarcomatoid carcinoma, carcinoma sarcomatoid, carcinoma with sarcomatoid features, and squamous carcinoma with sarcomatoid features. All patients with a final histopathological diagnosis of sarcomatoid variant of SCC (as confirmed by an oncopathologist) were identified and, based on the eligibility criteria and availability of clinical information, were finally included in the study. Clinical and demographic data including the age and sex of the patients, tumor location in the head-and-neck region, stage at presentation according to the American Joint Committee on Cancer 8th edition, treatment intent, details of treatment received, and their outcomes were recorded.

The diagnosis of sarcomatoid or spindle cell variant of SCC was arrived at after adequate histopathological examination as per the algorithm described by Viswanathan et al. for mucosal spindle cell neoplasms.[9] According to this algorithm, a diagnosis of sarcomatoid variant of SCC was made in the presence of an in situ component, dysplasia, or squamoid traits in mucosal malignant tumors. In the absence of these pathological features, immunohistochemical markers such as cytokeratin, epithelial membrane antigen, AE1/AE3, high-molecular-weight cytokeratin, p63, CD10, SMA, calponin, desmin, S100 protein, HMB45, and melan A were used to rule out the various differential diagnoses such as melanoma, neurogenic sarcoma, leiomyosarcoma, and myoepithelial carcinoma. If all the markers were negative in a spindle cell neoplastic lesion, a diagnosis of sarcomatoid variant of SCC (until proven otherwise) was made [Figure 1].
Figure 1: The histopathological features of the sarcomatoid variant of squamous cell carcinoma: (a) Spindle-to-stellate-shaped carcinoma cells infiltrating in a desmoplastic stroma. On immunohistochemistry, the tumor cells are positive for AE1/AE3 (b) and p40 (c) confirming epithelial and squamous differentiation

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Definitions

DFS was defined as the duration from treatment initiation to the first recurrence or death, whichever occurred earlier.

Statistics

As this was a retrospective study, no formal sample size calculation was performed and all patients fulfilling the eligibility criteria were included in the study. Statistical analysis was performed using the Statistical Package for the Social Sciences (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, version 21.0. Armonk, NY, USA: IBM Corp.). Variables were analyzed using simple descriptive statistical methods. DFS was calculated using the Kaplan–Meier method.


  Results Top


Baseline characteristics

A total of 177 patients were diagnosed with sarcomatoid carcinoma of the head-and-neck region between January 2012 and December 2018. Of these, 60 patients fulfilled the eligibility criteria [Figure 2] and were included in the study for analysis. The demographic characteristics of the patients are shown in [Table 1]. The median age of the patients was 51 years (range, 24–78). The majority of the patients were men (49, 81.6%). The most commonly affected site in the upper aerodigestive tract was the oral cavity in 29 (65%) patients, followed by the larynx and hypopharynx in a 13 (21.6%) patients [Figure 3]. A total of 38 patients used tobacco alone (63.3%), while 6 (10%) used tobacco with alcohol. A total of 43 (71.6%) patients had advanced stage (III/IV) disease at presentation. Patients with oral cancer frequently presented with advanced disease, whereas those with laryngeal cancer presented more often with early-stage disease.
Table 1: Clinical and demographic details of the patients

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Figure 2: Flow diagram delineating the inclusion and exclusion criteria of the study, (SVSCC: Sarcomatoid variant of squamous cell carcinoma; HPR: histopathology report)

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Figure 3: Clinical appearance of the disease

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Treatment

Out of 60 patients in the cohort, 41 (68.3%) received curative-intent treatment, while the remaining 19 (31.7%) received palliative therapy because of the advanced nature of the disease. Palliative treatment was provided due to an advanced inoperable primary tumor in 16 patients and the presence of distant metastasis at presentation in 3 patients [Table 1]. The details of the curative treatment received by the patients are provided in [Table 2].
Table 2: Details of treatment received by the patients

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Recurrences

The median follow-up for patients who received curative treatment was 29 months (range, 1–106). Among patients who received curative treatment, 12 (29.2%) developed recurrences, most commonly at a distant site [Table 1]. Nine out of these 12 patients received palliative chemotherapy or radiotherapy depending on the site or extent of the disease and the other 3 patients could undergo salvage treatment in the form of surgery [Table 1]. The DFS of patients who received curative treatment was 76.3 months (95% confidence interval [CI], 60.3–92.4), while that of patients who received palliative-intent treatment was 11.6 months (95% CI, 9.2–14) [Figure 4].
Figure 4: Disease-free survival of the patient cohort

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  Discussion Top


We found that the oral cavity was the most common anatomic subsite in the head-and-neck region among patients with sarcomatoid variant of SCC, and the majority presented with advanced-stage disease. Most patients received curative-intent treatment and had a median DFS of 76.3 months.

The sarcomatoid variant of SCC is considered to be an uncommon entity, composed of both epithelial and mesenchymal components. This is mainly due to the dedifferentiation associated with sarcomatoid transformation.[10],[11],[12] The most common etiological agents responsible for this transformation are tobacco and alcohol consumption, as seen with any other variant of SCC.[12] Many studies have also attributed prior exposure to radiation as a possible reason for the development of this type of cancer.[1],[13]

In previous studies, many sites other than the head-and-neck region such as the lung, breast, skin, prostate gland, and female reproductive tract have been reported to develop this form of malignancy.[14],[15],[16] However, the head-and-neck region has been reported to be the most commonly affected.[17] In the head-and-neck region, the most commonly affected site is the larynx followed by the oral cavity.[4],[5] However, considering the geographical location and patient demographics in India, sarcomatoid carcinoma affecting the oral cavity has been shown to be the most prevalent.[10] This can be attributed to the habit of chewing tobacco, which is more common in our region compared to other forms of tobacco use like smoking.[18] Similarly, in our study, the most common site of development of the sarcomatoid variant of SCC was the oral cavity, followed by the larynx and hypopharynx.

This variant of SCC is known to affect patients in their fifth to seventh decades of life, with men being affected more commonly than women (11:1).[1],[19] A similar trend was observed in our cohort, with the median age of the patients being 51 years. The variant commonly presents as a polypoidal fleshy tumor with a short duration of onset and rapid progression.[5] The majority of the patients in our cohort presented with advanced-stage disease. However, advanced stage at presentation is reported quite frequently even with other variants of SCC.[18],[20] Sarcomatoid carcinomas tend to have a more aggressive clinical course and higher mortality rates compared to other variants of SCC at a similar stage.[21],[22]

The histopathological features of these tumors often pose a diagnostic challenge, which in turn makes appropriate treatment decision-making more challenging. The most appropriate management plan to provide the highest chance of cure for the patient is based on the site of the tumor. Hence, for the sarcomatoid variant of SCC occurring in the oral cavity, surgery followed by adjuvant therapy, based on histopathological findings, is the mainstay of treatment.[8] Organ preservation protocols in the form of concurrent chemoradiation can be considered for advanced laryngeal and hypopharyngeal sarcomatoid variants of SCC.[23] Earlier, as this variant of SCC was considered to be resistant to radiation therapy, the efficacy of radiotherapy alone in the treatment of early-stage lesions was a matter of debate.[24] However, it was later shown that the use of radiation therapy alone in T1-T2 glottic sarcomatoid SCC can produce acceptable locoregional control rates.[25] In our study, treatment decisions were based on the site and clinical stage of the tumor. Another debate prevails regarding the effectiveness of adjuvant treatment in this variant of SCC. Contradictory reports exist regarding the benefit of adjuvant radiation therapy on the survival outcomes.[26],[27] Even with the use of aggressive treatment regimens, the recurrence rates and prognosis are poor for this subset of tumors. This is especially true in cases of oral cavity sarcomatoid carcinomas, where the overall survival and disease-specific survival have been shown to be much lower than those reported for conventional SCC.[28] Similarly, in our study, 29.7% of the patients developed recurrent disease despite receiving complete treatment, out of which only 3/12 (7.31%) patients could be salvaged. Furthermore, 6 of these patients (14.6%) presented with distant metastasis, and hence, received palliative treatment.

The current study helps us understand the pattern of presentation as well as the treatment given to patients with sarcomatoid carcinoma and its outcomes. In addition, it emphasizes the fact that it most commonly occurs in the oral cavity. However, our study had its limitations, which include the retrospective design and the small sample size. In addition, as the cohort included patients who were treated either with curative or palliative intent and as the primary aim of the study was to study the clinical presentation and the pattern of treatment, we did not assess the prognostic factors influencing the survival in our patients. We did not compare our cohort of patients with sarcomatoid SCC with patients diagnosed with the classic variant of SCC treated during that time period. It was beyond the scope of our study to assess for any biomarker levels, including the PD-L1 score or genomic characterization.


  Conclusions Top


Sarcomatoid variant of SCC of the head-and-neck region usually presents with advanced disease, however, has a reasonable DFS when treated appropriately with curative intent.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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