Submit Your Article CMED MEACR meeting
Home Print this page Email this page Users Online: 262
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
CASE REPORT
Year : 2018  |  Volume : 7  |  Issue : 5  |  Page : 187-190

Carcinosarcoma of the submandibular gland with a rhabdomyosarcoma component: A case report and review of the literature


Department of Pathology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India

Date of Web Publication10-Jan-2019

Correspondence Address:
Dr. Suma M Narayana
Department of Pathology, Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda Road, Bengaluru, Karnataka
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ccij.ccij_83_18

Rights and Permissions
  Abstract 


Carcinosarcoma of the salivary gland is a rare and aggressive malignancy with a poor prognosis. These neoplasms are composed of malignant epithelial and mesenchymal elements. This report describes a new case of carcinosarcoma arising in the submandibular gland, which had a rhabdomyosarcoma component, without clinical or histological evidence of a preexisting pleomorphic adenoma. Till date, only two case reports have described the occurrence of carcinosarcoma with a rhabdomyosarcoma component in the salivary gland, to the best of our knowledge. Histological and immunohistochemical results are presented. The literature is reviewed, and the possible histogenesis and pathogenesis of carcinosarcoma (true malignant mixed tumor) of the salivary gland are briefly discussed.

Keywords: Carcinosarcoma, rhabdomyosarcoma, salivary gland, submandibular gland, true malignant mixed tumor


How to cite this article:
Narayana SM, Singh S, Kumar RV. Carcinosarcoma of the submandibular gland with a rhabdomyosarcoma component: A case report and review of the literature. Clin Cancer Investig J 2018;7:187-90

How to cite this URL:
Narayana SM, Singh S, Kumar RV. Carcinosarcoma of the submandibular gland with a rhabdomyosarcoma component: A case report and review of the literature. Clin Cancer Investig J [serial online] 2018 [cited 2019 Mar 19];7:187-90. Available from: http://www.ccij-online.org/text.asp?2018/7/5/187/249816




  Introduction Top


Carcinosarcoma of the salivary gland is a rare and aggressive malignancy with a poor prognosis. Around 70 cases have been described in the literature. These neoplasms are composed of malignant epithelial and mesenchymal elements. This report describes a new case of carcinosarcoma arising in the submandibular gland with a rhabdomyosarcoma component, without clinical or histological evidence of a preexisting pleomorphic adenoma. Till date, only two case reports have described carcinosarcoma with a rhabdomyosarcoma component in the salivary glands.[1],[2] Both were in the parotid gland.


  Case Report Top


A 50-year-old male presented with a left-sided submandibular swelling for 6 months, with a rapid increase in size for 2 months. He also had complaints of difficulty in breathing. Examination revealed a large, firm, mobile mass. Ultrasound of the neck demonstrated a 7-cm homogenous mass with well-defined margins and posterior acoustic enhancement. Computed tomography (CT) revealed a homogenous mass in the left submandibular gland extending into the adjacent muscle. Following contrast, there was marked homogeneous enhancement greater than that of the normal submandibular gland parenchyma and muscle. The margins were well defined. CT chest revealed bilateral lung metastases. Fine-needle aspiration of the mass showed clusters of spindle-shaped cells with moderate to marked atypia and few epithelial cells showing increased nuclear-to-cytoplasmic ratio with coarse chromatin, in a background of necrosis. Extensive workup did not reveal any other malignancy.

The patient underwent total excision of the left submandibular gland mass and left modified radical neck dissection. The resected specimen was sent for histopathological examination.

Formalin-fixed, paraffin-embedded sections were examined with routine hematoxylin and eosin stain. Immunohistochemistry (IHC) was performed on 3 μ sections cut from paraffin blocks according to the manufacturer's instructions. The antibodies used are given in [Table 1].
Table 1: Details of the antibodies used

Click here to view


Grossly, the excised submandibular gland mass measured 16 cm × 7 cm × 6 cm. The mass was encapsulated and the external surface was nodular. Cut surface revealed a gray-white tumor measuring 6 cm × 6 cm × 5 cm with areas of hemorrhage and necrosis [Figure 1]a.
Figure 1: (a) Cut surface of the tumor showing gray-white areas; (b) section shows tumor cells forming glandular structures with an adjacent spindle cell component (H and E, ×10); (c) spindle cells arranged in intersecting fascicles (H and E, ×10); (d) tumor cells with large vesicular nuclei, prominent nucleoli with a rhabdomyoblast in the center (arrow) (H and E, ×40)

Click here to view


Microscopically, the tumor was composed of two components – carcinoma and sarcoma. The former was that of adenocarcinoma with neoplastic cells arranged in a glandular pattern [Figure 1]b. The latter was mainly composed of malignant spindle to ovoid cells in sheets and fascicles resembling fibrosarcoma [Figure 1]c. Frequent mitoses (>20/10 hpf) with areas of necrosis were present. Foci of rhabdomyosarcoma, containing sheets and clusters of cells with abundant eosinophilic cytoplasm and eccentric round nuclei, were observed [Figure 1]d. Fourteen regional lymph nodes were negative for tumor. No coexisting pleomorphic adenoma component was identified.

Both the carcinoma and sarcoma cells were positive for cytokeratin (CK) and negative for CD10 [Figure 2]a. The carcinoma cells were strongly positive for CK 5/6 [Figure 2]b and weakly positive for epithelial membrane antigen (EMA) [Figure 2]c. P63 was positive in scattered spindle cells [Figure 2]d. The spindle cells were strongly positive for vimentin [Figure 3]a an[Figure 3]d desmin [Figure 3]b but were negative for CD34, CD31, S100, and H-caldesmon. The rhabdomyosarcoma cells were positive for myogenin [Figure 3]c. Ki67 proliferation index was more than 80% [Figure 3]d.
Figure 2: (a) Tumor cells positive for cytokeratin in both the carcinoma and sarcoma components (×10); (b) tumor cells of the adenocarcinoma component strongly positive for cytokeratin 5/6 (×10); (c) tumor cells weakly positive for epithelial membrane antigen (×40); (d) tumor cells showing scattered positivity for p63 (×10)

Click here to view
Figure 3: (a) Tumor cells weakly positive for vimentin (×10); (b) tumor cells strongly positive for desmin (×10); (c) tumor cells showing nuclear positivity for myogenin (×40); (d) tumor cells showing nuclear positivity in >80% of the cells for Ki67 (×10)

Click here to view


The patient developed respiratory complications due to lower respiratory tract infection, 6 weeks after the surgery and passed away.


  Discussion Top


Carcinosarcoma is a malignant tumor composed of a mixture of both carcinomatous and sarcomatous elements. It is also known as true malignant mixed tumor. Carcinosarcoma of the salivary glands is a rare tumor with about 70 cases reported in the literature.[1],[2],[3],[4] Carcinosarcoma of the salivary glands was first described by Kirklin et al. in 1951.[3] Carcinosarcoma is an extremely rare and aggressive tumor.[4] It accounts for only 0.04%–0.16% of all salivary gland tumors.[2] The patients' age range from 14 to 87 years.[4] There is no gender predilection. Many patients had a history of recurrent pleomorphic adenoma, and several cases have developed in a preexisting pleomorphic adenoma (carcinosarcoma ex pleomorphic adenoma).[5],[6],[7],[8] Some cases, however, arose de novo, in the absence of a previous pleomorphic adenoma.[4],[9] The etiology is unknown. Accumulation of genetic mutations such as loss of heterozygosity (LOH) at 17p13.1, 17q21.3, and 18q21.3 could be a factor. Allelic losses in three genetic loci were seen to occur at high rates: 17p13, which is the location of the p53 gene (73% of targets), 17q in the location of the nm-23 gene (55% of targets), and 18q in the location of the DCC gene (50% of targets).[10],[11] Irradiation of pleomorphic adenoma has also been implicated as an etiologic factor.[8] Two schools of thought exist as to the origin of carcinosarcomas. The convergence hypothesis states that polyclonal stem cells of the epithelial and mesenchymal components play a causative role. The divergence hypothesis postulates a monoclonal origin from a single totipotent stem cell with divergent differentiation.[12] Götte et al. hypothesized that the tumor originated from a myoepithelial cell precursor.[13] Other authors have postulated that the tumor originates from inner ductal cells or a pluripotent primitive cell.[6] In the cases reported, majority (66%) occurred in the parotid gland, followed by the submandibular gland (19%), and the minor salivary glands in the palate (14%).[3],[4],[5] Other sites include the cheek, tongue, and the supraglottis.[3],[4],[5]

The tumor often presents as a rapidly enlarging mass that may or may not be associated with pain. If the parotid gland is involved, signs of facial nerve palsy are commonly seen.

Macroscopically, the neoplasm is either well delineated or poorly circumscribed with infiltrative borders. Focal areas of hemorrhage and necrosis may be present. Microscopically, it is characterized by the presence of two malignant components – an epithelial (carcinomatous) and a mesenchymal (sarcomatous) component. The carcinomatous component is usually a poorly differentiated adenocarcinoma, an undifferentiated carcinoma, or a squamous cell carcinoma, and the sarcomatous component is usually a chondrosarcoma.[4] However, the sarcomatous component in the reported cases is varied and includes spindle cell sarcoma not otherwise specified, fibrosarcoma, osteosarcoma, and rhabdomyosarcoma.[2],[4],[5],[9] Perineural invasion, angioinvasion, and tissue destruction are common. Lymphatic spread is less common.[3]

The immunohistochemical profile varies depending on the observed components of the tumor. Usually, the carcinomatous component is positive for CK and EMA, and the sarcomatous component is vimentin positive. However, in very poorly differentiated tumors, the carcinomatous component may show only focal or weak-positive staining for cytokeratins or EMA.

The prognosis of these tumors remains unfavorable, with rates of mortality at 5 years varying between 48% and 100%. This is clearly worse in comparison with that of carcinoma ex pleomorphic adenoma, probably because of the absence of the sarcomatous component.[14]

In a review by Gnepp, 58% of patients died as a result of the tumor.[4] Staffieri et al., in a review of 19 cases of de novo carcinosarcomas, found that 31.6% of patients died of the tumor.[9] The median period of survival after the diagnosis was 10 months.[9] In 63% of cases, there was no evidence of recurrence after a median period of 22.4 months.[9]

Although ultrasonography and CT scan are essential, the histologic examination is crucial to establish a definitive diagnosis.

Regarding therapy, the data in the available literature suggest that surgical resection (histologically negative margins) should always be associated with neck dissection including levels I, II, III and IV, and adjuvant radiotherapy. Some authors have suggested the combination of adjuvant chemotherapy with adjuvant radiotherapy.[3] However, the role of chemotherapy has not been well established.


  Conclusion Top


It can be seen from the review of literature that carcinosarcoma of the salivary gland is a rare neoplasm with rapid disease progression and an unfavorable prognosis. Even rarer is carcinosarcoma with a rhabdomyosarcoma component in the salivary gland, with only two case reports in the English literature. To establish a definite diagnosis and provide suitable therapy, histological examination and IHC are essential and help to rule out benign neoplasms, the exclusively epithelial malignant tumors of the salivary glands and submandibular and/or parotid lymph node metastases.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Gandour-Edwards RF, Donald PJ, Vogt PJ, Munn R, Min KW. Carcinosarcoma (malignant mixed tumor) of the parotid: Report of a case with a pure rhabdomyosarcoma component. Head Neck 1994;16:379-82.  Back to cited text no. 1
    
2.
Kwon MY, Gu M. True malignant mixed tumor (carcinosarcoma) of parotid gland with unusual mesenchymal component: A case report and review of the literature. Arch Pathol Lab Med 2001;125:812-5.  Back to cited text no. 2
    
3.
Kirklin JW, McDonald JR, Harrington SW, New GB. Parotid tumors; histopathology, clinical behavior, and end results. Surg Gynecol Obstet 1951;92:721-33.  Back to cited text no. 3
    
4.
Gnepp DR. Malignant mixed tumors of the salivary glands: A review. Pathol Annu 1993;28 Pt 1:279-328.  Back to cited text no. 4
    
5.
Stephen J, Batsakis JG, Luna MA, von der Heyden U, Byers RM. True malignant mixed tumors (carcinosarcoma) of salivary glands. Oral Surg Oral Med Oral Pathol 1986;61:597-602.  Back to cited text no. 5
    
6.
Alvarez-Cañas C, Rodilla IG. True malignant mixed tumor (carcinosarcoma) of the parotid gland. Report of a case with immunohistochemical study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;81:454-8.  Back to cited text no. 6
    
7.
Hellquist H, Michaels L. Malignant mixed tumour. A salivary gland tumour showing both carcinomatous and sarcomatous features. Virchows Arch A Pathol Anat Histopathol 1986;409:93-103.  Back to cited text no. 7
    
8.
Spraggs PD, Rose DS, Grant HR, Gallimore AP. Post-irradiation carcinosarcoma of the parotid gland. J Laryngol Otol 1994;108:443-5.  Back to cited text no. 8
    
9.
Staffieri C, Marioni G, Ferraro SM, Marino F, Staffieri A. Carcinosarcoma de novo of the parotid gland. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:e35-40.  Back to cited text no. 9
    
10.
Fowler MH, Fowler J, Ducatman B, Barnes L, Hunt JL. Malignant mixed tumors of the salivary gland: A study of loss of heterozygosity in tumor suppressor genes. Mod Pathol 2006;19:350-5.  Back to cited text no. 10
    
11.
Vékony H, Leemans CR, Ylstra B, Meijer GA, van der Waal I, Bloemena E, et al. Salivary gland carcinosarcoma: Oligonucleotide array CGH reveals similar genomic profiles in epithelial and mesenchymal components. Oral Oncol 2009;45:259-65.  Back to cited text no. 11
    
12.
Bhalla RK, Jones TM, Taylor W, Roland NJ. Carcinosarcoma (malignant mixed tumor) of the submandibular gland: A case report and review of the literature. J Oral Maxillofac Surg 2002;60:1067-9.  Back to cited text no. 12
    
13.
Götte K, Riedel F, Coy JF, Spahn V, Hörmann K. Salivary gland carcinosarcoma: Immunohistochemical, molecular genetic and electron microscopic findings. Oral Oncol 2000;36:360-4.  Back to cited text no. 13
    
14.
Qureshi A, Barakzai A, Sahar NU, Gulzar R, Ahmad Z, Hassan SH, et al. Spectrum of malignancy in mixed tumors of salivary gland: A morphological and immunohistochemical review of 23 cases. Indian J Pathol Microbiol 2009;52:150-4.  Back to cited text no. 14
[PUBMED]  [Full text]  


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Case Report
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed163    
    Printed3    
    Emailed0    
    PDF Downloaded5    
    Comments [Add]    

Recommend this journal