Confirmed laryngeal sarcomatoid carcinoma after three vocal cord surgeries in a short period of time: A case report and literature review

  • Authors:
    • Di Ji
    • Xinyu Liang
    • Li Zhao
    • Xianbai Zhu
    • Junjie Yang
    • Bo Liu
    • Anchun Deng
    • Xueqin Zhou
  • View Affiliations

  • Published online on: October 3, 2024     https://doi.org/10.3892/ol.2024.14718
  • Article Number: 584
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Abstract

Sarcomatoid carcinoma is a rare disease, while larynx sarcomatoid carcinoma is a rarer type of cancer characterized by high malignancy and rapid growth. This type of cancer is prone to misdiagnosis and recurrence. The present case study aimed to provide a detailed report on the diagnosis and treatment of a male patient who underwent three tumor resections in the same location of the vocal cords within a short time. Immunohistochemical analysis was not performed after the first two surgeries at other hospitals, thus resulting in an inconclusive diagnosis. Within a short time, it was suspected that the patient experienced local recurrence, thus rapidly leading to the onset of grade III laryngeal obstruction symptoms. During his last visit to the Second Affiliated Hospital of the Army Military Medical University Outpatient Department (Chongqing, China), a biopsy was carried out and tissue samples were collected for immunohistochemical examination. The diagnosis of larynx sarcomatoid carcinoma was therefore verified. Subsequently, partial laryngectomy combined with laryngeal functional reconstruction and left neck lymph node dissection were performed. Post‑surgery immunohistochemical analysis also verified larynx sarcomatoid carcinoma. During the 6‑month follow‑up, there was no evidence of metastasis or recurrence.

Introduction

Sarcomatoid carcinoma is a rare neoplasm with distinct cellular differentiation (18). It is considered as a more aggressive variant of squamous cell carcinoma in the head and neck region (18). Due to limited literature, there are currently no clear and unified diagnostic and treatment guidelines for laryngeal sarcomatoid carcinoma (9). This malignancy can occur in various anatomical sites, including the upper respiratory tract, lungs, breast, skin, gastrointestinal tract and the urogenital system (10). However, it most commonly affects the lungs (1115). Laryngeal sarcomatoid carcinoma is rare (1,2,16), accounting for 2–3% of all laryngeal cancers (3), with glottis being the most common site affected, with an incidence of ~1.5% of all laryngeal-related cancers (4). Although lymph node metastasis and distant spread are relatively uncommon in laryngeal sarcomatoid carcinoma, the recurrence rates remain high (57).

Squamous cell carcinoma originates from the epithelium, whereas sarcoma arises from the mesenchyme. Carcinosarcoma is a biphasic tumor comprising either in situ or invasive squamous cell carcinoma and a malignant spindle cell component of epithelial origin, showing mesenchymal characteristics (18). It is considered as an aggressive variant of squamous cell carcinoma (18). Due to their morphological and immunohistochemical similarities, pathologists face significant challenges in differentiating carcinosarcoma from spindle cell sarcoma (17,18). Therefore, the rate of misdiagnosis is high and this type of tumor is often mistaken with vocal cord polyps or laryngeal squamous cell carcinomas (9,10).

In the present study, the case of a patient who underwent two vocal cord tumor resection surgeries in another hospital, followed by partial resection of the larynx combined with laryngeal functional reconstruction surgery in the Second Affiliated Hospital of the Army Military Medical University (Chongqing, China) was reported. Shortly after each surgery, signs of recurrence at the surgical site were suspected. Histopathological and immunohistochemical examinations on tumor specimens verified sarcomatoid carcinoma of the larynx and, therefore, a third surgery on the larynx was performed. After surgery, the patient was followed up for an additional 6 months and no signs of recurrence were observed.

The analysis of the present case study could assist clinical practitioners in drawing from relevant experiences, reducing misdiagnosis rates for laryngeal sarcomatoid carcinoma and achieving early detection and diagnosis.

Case report

The present study reports the case of a 69-year-old male patient. Approximately 18 months prior admission to the Second Affiliated Hospital of the Army Military Medical University (Chongqing, China), the voice of the patient remained hoarse after contracting a cold, while the medication treatment was not satisfactory. At 16 months prior admission, the patient sought medical attention in the People's Hospital of Hechuan Chongqing (Chongqing, China) and underwent surgical resection of vocal cord lesions under laryngoscopy. Postoperative pathological diagnosis revealed inflammatory granulation tissue and a small amount of fibrinous exudate in the vocal cords. However, no further immunohistochemical examinations were performed. At 14 months prior admission, although the patient reported improved postoperative hoarseness, the patient subsequently experienced a recurrence of persistent hoarseness and morning voice loss. Laryngoscopy revealed the regrowth of the mass in the surgical area. Therefore, at 11 months prior admission, the patient was subjected to an endoscopic excision procedure to support the removal of the vocal cord mass. The postoperative pathological diagnosis still indicated inflammatory granulation tissue with multinucleated giant cell reaction in the left vocal cord mass. However, no additional immunohistochemical examination was conducted. At 1 month after the second surgery, the patient experienced a recurrence of hoarseness in his voice. However, no further medical intervention was applied. Furthermore, at 1 month prior to admission, the patient suddenly developed symptoms of grade III laryngeal obstruction, which required immediate medical attention. To alleviate respiratory distress, the patient underwent tracheostomy. Subsequently, the patient sought further treatment by our medical team at the Second Affiliated Hospital of the Army Military Medical University in November 2023.

Therefore, the patient was first subjected to throat spiral computed tomography. The results revealed a tumor mass of ~1.9×1.7 cm2 in size (Fig. 1A-E). Additionally, as shown in Fig. 1D and E, complete obstruction at the glottis level in the larynx was observed, which directly resulted in the patient's sudden onset of upper airway obstruction prior to hospital admission. In addition, laryngoscopy followed by biopsy was performed at the tumor site. Laryngoscopic images were captured at 1 month and 1 day prior to surgery. The tumor displayed a polypoid growth pattern, occupying a substantial portion of the glottis with localized expansion, smooth surface and absence of evident ulceration or secretion (Fig. 2A and B).

The significant increase in tumor size within <1 month between both laryngoscopic examinations aligned with the findings from previous imaging studies and further underscored the characteristic features of sarcomatoid carcinoma of the larynx, namely high malignancy and rapid progression. Then, at 5 days prior surgery the patient was subjected to neck magnetic resonance imaging scan with both plain and enhanced scans. The results showed that the tumor size was ~2.8×1.9 cm2 (Fig. 3A-D), which signified a significant increase compared with the spiral CT results obtained 1 month prior, thereby highlighting the rapid tumor progression rate. In addition, immunohistochemical pathological analysis of preoperative outpatient tumor biopsy sections taken 1 month prior to surgery under local anesthesia was performed using rapid paraffin-embedded tissue sections [Fig. 4A, Image 1 of the preoperative biopsy paraffin section indicating nuclear atypia and typical spindle-shaped cells; Fig. 4B, Image 2 of the preoperative biopsy immunohistochemistry showing positivity for cytokeratin (CK) and vimentin]. Eventually, based on its morphology and immunophenotyping, the patient was diagnosed with laryngeal sarcomatoid carcinoma. The laryngeal tumor was classified as T2N0M0, according to the established criteria of the TNM staging system (19).

Based on the aforementioned findings, the patient underwent partial laryngectomy and left neck lymph node dissection with concurrent functional reconstruction of the larynx under general anesthesia. The surgical procedure was carried out as follows: A transverse incision in the shape of a ‘T’ was created using a tungsten needle, thus gradually dissecting through the layers of the skin, subcutaneous tissue and platysma myoides. The left sternocleidomastoid muscle was then carefully separated to access and examine the lymph nodes adjacent to the carotid sheath for clearance purposes. No significantly enlarged lymph nodes were identified during this process. To expose the thyrohyoid membrane, an incision was made on the thyroid cartilage, cutting along the midline. From there, the incision was continued downwards to reach the cricoid membrane. Subsequently, a vertical incision at the posterior part of the thyroid cartilage on the side of the tumor was created, while preserving a narrow strip of cartilage, 3–5 mm in width, connecting its upper and lower angles. The laryngeal ventricle was accessed from the contralateral side through a cartilage incision, thus revealing an extensive neoplasm involving the left laryngeal ventricle, the vestibular fold and the vocal cord. The tumor was excised at a vertical angle and specimens of the left upper, left lower, right and posterior margins were collected for intraoperative frozen section analysis. The analysis results were all negative for malignancy. The vocal fold function was ultimately restored through the use of absorbable thread to suture the thyroid cartilage membrane, reconstruction of the laryngeal cavity with a strap muscle flap and subsequent alignment suturing of the anterior strap muscles.

The tumor images captured intraoperatively revealed that the tumor was spherical in shape with distinct sarcoma-like characteristics, completely occupying the laryngeal space (Fig. 5A and B). In addition, frozen section pathology examinations of the tumor margin tissue revealed that there were no cancer cells, thus indicating that complete resection was achieved. The results of the intraoperative frozen section biopsy of the upper left, lower left, right and posterior margins of the tumor are depicted in Fig. 4C and D.

Postoperatively, histopathological analysis of paraffin sections verified the diagnosis as laryngeal sarcomatoid carcinoma without any evidence of cancer cells in the lymph nodes [paraffin embedding of tissues (10% neutral formalin; temperature, 25°C; duration, 24 h), immunohistochemical sections were prepared with a thickness of 3 µm and routine HE staining with a thickness of 4 µm; blocking reagent, 3% H2O2; temperature, 37°C; duration, 4 min (BenchMark ULTRA IHC/ISH Staining Module, Ventana Medical Systems, Inc., used according to the manufacturer's instructions); microscope, Leica DM1000LED (Leica Microsystems GmbH].

More specifically, the postoperative pathological and immunohistochemical analyses were performed using monoclonal antibodies, special staining [Gomori's silver ammonium hydroxide staining method; Henan Sainuote Biotechnology Co.; Yu Zheng Food and Drug Administration Equipment Production Record no. 20140010 (updated)] and enzyme histochemistry (Fig. 4E and F). The tumor tissue was positive for the epithelial immunohistochemical marker CK and the sarcomatoid tissue-related marker vimentin, thus verifying the diagnosis of laryngeal carcinosarcoma. No tumor cells were found in the neck lymph node biopsy, thus suggesting that metastasis did not occur in the neck lymph nodes. The immunohistochemical protocol referred to the study by De Stefani et al (6) and Heidarian and Wenig (17) and experimental and antibody details are provided in Fig. S1.

The reticulin staining was positive (temperature, 25°C; duration, potassium permanganate solution oxidized for 5 min; oxalic acid solution bleached for 1–3 min; ammonium iron sulfate solution stained for 3–5 min; silver ammonia solution stained for 3–5 min; formaldehyde solution restored for 2–3 min; gold chloride solution reacted for 30 sec; sodium thiosulfate solution reacted for 2 min).

The patient received symptomatic supportive therapy after surgery and recovered well. The patient was discharged on the 10th day after surgery. Laryngoscopic follow-up examinations were performed on days 7 and 20, and on the 3rd and 6th months after surgery (Fig. 2C-F). The results showed good healing of the surgical site, with no signs of tumor recurrence. Therefore, after 20 days of surgery, the follow-up laryngoscopy showed good postoperative recovery. Consequently, radiotherapy was deemed unnecessary. Subsequent follow-up examinations in June 2024, the 6th month after surgery, indicated significant improvement in the patient's condition. Currently, there is no evidence of tumor recurrence or metastasis.

Discussion

The nature of sarcomatoid carcinoma has long been a subject of controversy. Several hypotheses have been proposed regarding its histogenesis, including the theories of metaplasia, collision, embryonic remnants and pluripotent stem cells. As a result, there are multiple terms used to describe sarcomatoid carcinoma, including carcinosarcoma, pleomorphic carcinoma, spindle cell carcinoma, carcinoma in a sarcomatoid stroma and sarcomatoid carcinoma (20,21). Currently, there is a growing consensus on the transformation of squamous epithelial cancer into sarcomatoid components. Therefore, sarcomatoid carcinoma is now widely accepted as the preferred terminology.

In a previous retrospective study of 103 patients with sarcomatoid carcinoma in the head and neck region, the proportion of laryngeal cancer was the second highest (17.5%), behind only to that of oral cavity cancer (63.1%) (16). Between 2004 and 2007, a total of 171 spindle cell tumors were reported at the pathology department of this hospital (Tata Memorial Hospital, Parel, Mumbai, India), with 103 cases diagnosed as sarcomatoid carcinoma, accounting for ~70% (16). Among them, 95% of patients had symptoms lasting <1 year. Follow-up data from 39 patients confirmed eight cases of recurrence, two cases of distant metastasis and three deaths. The most common sites of metastasis were the lungs (4), followed by the lymph nodes (16). The metastatic components included conventional squamous cell carcinoma, sarcomatoid carcinoma or a combination of both (17). Sarcomatoid carcinoma predominantly affects the glottis within the larynx, accounting for ~72% of all cases (4). Hoarseness of voice is the most common initial symptom of sarcomatoid carcinoma. However, coughing and breathing difficulties can also occur in the later stages (18). Another study also reported a mortality rate ranging from 18 to 32% for this disease (16). In the present study, the follow-up period was still short and therefore further monitoring of prognosis is needed. Sarcomatoid tumors often present as polypoid growths or ulcerative lesions, which is consistent with the findings of the large polypoid protrusions within the airway observed in the present case. Sarcomatoid carcinoma usually occurs between the ages of 20–90 years, mainly affecting men, while the highest incidence is observed in individuals aged 50–60 years (16). Consistently, in the present study the case of male patient aged between 50 and 60 years was reported.

There are several risk factors associated with the development of sarcomatoid carcinoma, including tobacco use (both smoking and chewing), alcohol consumption, exposure to radioactive substances and contact with toxic chemicals. Among these risk factors, chewing tobacco is the most significant, followed by smoking (16). In this particular case, the patient had a prolonged history of smoking, which aligns with previous findings.

Sarcomatoid carcinoma typically presents as a large polypoid neoplasm, with or without the presence of ulceration (22). Fibrinogen deposits can be also present on the surface (4). A case study documented a massive tumor-like carcinoma lesion in the throat, with a volume of 6×5×3 cm3 (3). In the present study, the tumor size was 2.8×1.9 cm2. Under microscopic examination, sarcomatoid carcinoma displays prominent atypical spindle-shaped and polygonal cells, with a diffuse distribution pattern. In particular areas with transitional zones, nest-like structures could occasionally be observed.

In cases where conventional squamous cell carcinoma components cannot be identified histologically, the diagnosis of the disease primarily relies on rapid paraffin sectioning combined with immunohistochemistry (17). However, in a previous study, sarcomatoid carcinoma was misdiagnosed as vocal cord polyps or other tumors based solely on rapid paraffin sections (9). The monoclonal nature of carcinosarcoma cells has been well established, thus supporting their origin from the transformation of squamous cell carcinoma into sarcomatoid differentiation. It has been reported that these cells exhibit positive expression of several epithelial-related immunohistochemical markers, including CK(AE1/AE3), epithelial membrane antigen, keratin (K)I and K18 (57). Additionally, carcinosarcoma cells can display positivity for the sarcomatoid tissue-related immunohistochemical markers, vimentin and K (1,2). However, the occasional aberrant expression of mesenchymal markers can also lead to misdiagnosis. Furthermore, emerging evidence has suggested that sarcomatoid carcinoma cells can carry intricate genetic alterations. Therefore, Choi et al (1) reported a consistent phenomenon of heterozygous deletion or retention in 80% of sarcomatoid carcinoma cases. Furthermore, the study (1) supported the notion that sarcomatoid carcinoma could be evolved from conventional squamous cell carcinoma, thus verifying the malignant nature of the sarcomatoid component, eventually supporting the sarcomatoid transformation-related molecular progression. Ki67 serves as an indicator of cellular proliferation. Therefore, a higher Ki67 rate is associated with poorer tissue differentiation, accelerated cell growth and enhanced tumor development (9). In the current case, the Ki67 expression rate was 70%, accompanied by rapid tumor growth over a short period of time. The aforementioned findings clearly verified the rapid growth of the sarcomatoid tumor. Therefore, an extended follow-up period is necessary.

As widely acknowledged, early tumor diagnosis plays a pivotal role in distinguishing sarcomatoid tumors from other benign and malignant tumors, such as leiomyosarcoma, malignant fibrous histiocytoma, reactive or benign spindle cell proliferation, malignant peripheral nerve sheath tumor and synovial sarcoma (monophasic type) (23). Therefore, the early diagnosis directly affects the extent of surgical intervention and treatment approach. The diagnostic criteria for distinguishing sarcoma from other types of cancer can be as follows (23): i) Malignant fibrous histiocytoma exhibits a complex cellular composition with pleomorphism, primarily consisting of fibroblasts and histiocytes arranged in a ‘spoke-wheel’ pattern. These tumor cells do not commonly express CK. ii) Leiomyosarcoma is characterized by larger and tightly arranged cells, with frequent mitotic figures. Immunohistochemical staining shows positivity for diethylstilbestrol and actin expression, but not for CK. iii) Malignant peripheral nerve sheath tumor presents spindle-shaped tumor cells with wavy or dot-like nuclei, without significant atypia. Immunohistochemical testing commonly displays positive expression of S100, Leu-7 and myelin basic protein (23). Pathologists should also be aware of reported cases of laryngeal carcinosarcoma with heterologous of striated muscle cells components (3), as this information is significant in the field.

Currently, there are no particular treatment guidelines or expert consensus available for laryngeal carcinosarcoma. However, surgical resection is considered the primary treatment approach, with radiotherapy being recommended as an adjunctive treatment option based on staging (24,25). It has been proposed that postoperative radiotherapy can be beneficial for patients with positive surgical margins, since their survival outcomes are comparable with those with negative ones (26). However, a previous study reported rapid systemic metastasis in patients with laryngeal sarcomatoid carcinoma following radiotherapy (27). By contrast, a retrospective analysis compared the data of 187 patients with laryngeal sarcomatoid carcinoma treated solely by surgery with those of patients who underwent surgery combined with postoperative radiotherapy, with a follow-up period of 7.7 and 6.7 years, respectively. The analysis revealed that the former had an improved prognosis (4). Several proponents advocate primary local radiotherapy for patients with stage T1 and T2 glottic carcinoma, aiming to optimize vocal function preservation. For patients with stage T3 and T4 glottic carcinoma, partial or total laryngectomy is recommended as the primary treatment modality, accompanied by postoperative radiotherapy (4). A study by the Mayo Clinic indicated that surgical treatment alone for advanced laryngeal sarcomatoid carcinoma had a higher recurrence rate, reaching 39% (8). According to previous reports, the 5-year survival rate of patients with laryngeal sarcomatoid carcinoma after surgery can exceed 70% (3,4,28).

The reasons for the previous two pathological diagnosis errors can be as follows: i) According to the theory supported by the majority of studies (18), laryngeal sarcomatoid carcinoma can evolve from squamous cell carcinoma. The first two events can occur during the process of epithelial hyperplasia prior its differentiation into cancer. Therefore, only inflammatory granulomatous lesions can be observed on the pathological examination. ii) During the early stage of the disease, the tumors are characterized by a small volume. Therefore, it is difficult to obtain tissue samples. The pathological tissue sampling is relatively superficial, resulting in failure to obtain truly cancerous tissues or obtaining very few ones. The specimens mainly consist of inflammatory tissues of the surface of the tumor, leading to misdiagnosis. In addition, early throat tumors exhibit well-defined boundaries, a smooth surface and small dimensions, and they can be therefore misdiagnosed as benign tumors. And iii) the main factor leading to misdiagnosis is the lack of immunohistochemical analysis, which is required to identify rapidly progressing vocal cord lesions.

In the present study, the patient underwent three consecutive vocal cord tumor resections within a short period of time. However, it was unacceptable that immunohistochemical examination was not performed in the first two surgeries. Without these tests, establishing a definitive diagnosis and determining whether the subsequent development of sarcomatoid carcinoma in the surgical area was due to missed diagnoses in the previous pathologies or simply due to disease progression could be challenging. Therefore, due to the lack of evidence, the cause of sarcomatoid carcinoma cannot be determined. The literature review highlighted that there can be a significant misdiagnosis rate in cases where laryngeal sarcomatoid carcinoma is misdiagnosed as vocal cord polyps or other types of tumors, followed by surgical resection (10). Therefore, clinicians should pay close attention to the management of recurrent vocal cord polyps or masses, particularly in patients without habitual voice use and with a prolonged history of smoking. Special consideration should be given in cases where rapid growth of vocal cord masses is observed. The tissue should be excised intact for paraffin section examinations, followed by immunohistochemistry, to rule out conditions, such as sarcomatoid carcinoma. Further surgical resection should be considered based on the results of postoperative pathology. Clarifying the nature of the tumor necessitates the utilization of intraoperative frozen section pathological tests for guidance, while ensuring that the tumor margin tissue is sent for pathological examination to further ensure complete tumor resection.

Supplementary Material

Supporting Data

Acknowledgements

Not applicable.

Funding

This study was funded by The Key Project of the Youth Doctoral Program at the Second Affiliated Hospital of the Army Military Medical University: Screening and Validation of Urinary Protein Biomarkers for Obstructive Sleep Apnea-Hypopnea Syndrome (grant no. 2023YQB031).

Availability of data and materials

The data generated in the present study may be requested from the corresponding author.

Authors' contributions

AD and XZ conceived and designed the work. DJ, XL and LZ acquired the data. JY, BL and XZ analyzed and interpreted the data. DJ and XL drafted the manuscript. All authors read and approved the final manuscript. DJ and XL confirm the authenticity of all the raw data.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Written consent from the patient has been obtained for all quoted information and associated patient images.

Competing interests

The authors declare that they have no competing interests.

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Spandidos Publications style
Ji D, Liang X, Zhao L, Zhu X, Yang J, Liu B, Deng A and Zhou X: Confirmed laryngeal sarcomatoid carcinoma after three vocal cord surgeries in a short period of time: A case report and literature review. Oncol Lett 28: 584, 2024.
APA
Ji, D., Liang, X., Zhao, L., Zhu, X., Yang, J., Liu, B. ... Zhou, X. (2024). Confirmed laryngeal sarcomatoid carcinoma after three vocal cord surgeries in a short period of time: A case report and literature review. Oncology Letters, 28, 584. https://doi.org/10.3892/ol.2024.14718
MLA
Ji, D., Liang, X., Zhao, L., Zhu, X., Yang, J., Liu, B., Deng, A., Zhou, X."Confirmed laryngeal sarcomatoid carcinoma after three vocal cord surgeries in a short period of time: A case report and literature review". Oncology Letters 28.6 (2024): 584.
Chicago
Ji, D., Liang, X., Zhao, L., Zhu, X., Yang, J., Liu, B., Deng, A., Zhou, X."Confirmed laryngeal sarcomatoid carcinoma after three vocal cord surgeries in a short period of time: A case report and literature review". Oncology Letters 28, no. 6 (2024): 584. https://doi.org/10.3892/ol.2024.14718