Introduction
Leiomyosarcomas are rare, accounting for only 4 per cent of head and neck sarcomas.Reference Pfeiffer, Boedeker, Ridder, Maier and Kayser1, Reference Takahashi, Higo, Nakata and Sugasawa2 They are malignant mesenchymal tumours and are most commonly seen within the gastrointestinal tract.Reference Ulrich, Feiz-Erfan, Spetzler, Isaacs, Hott and Nakaji3 In the head and neck, leiomyosarcomas have been reported within the larynx, cervical oesophagus, skin, sinonasal tract and oral cavity, with most cases arising from the latter two sites.Reference Ramkrishnan, Said and Kingdom4, Reference Maronio, Bertino, Mariuzzi, Berhamin-Bracale, Lombardo and Beltrami5 Risk factors include previous irradiation and immunosuppression.Reference Pfeiffer, Boedeker, Ridder, Maier and Kayser1, Reference Ramkrishnan, Said and Kingdom4, Reference Grabowska, Zimnoch, Hubert, Duraj and Wincewicz-Pietrzykowska6
We report a case of leiomyosarcoma arising from the tonsil in a 73-year-old man. Our patient presented with a short history of haemoptysis and unilateral odynophagia, with no identifiable risk factors. Clinical examination revealed an ulcerated lesion in the tonsil, and histological examination confirmed the diagnosis of leiomyosarcoma. To our knowledge, this is the first reported case in the English language literature of leiomyosarcoma arising from the tonsil.
Case report
A 73-year-old, male, ex-pipe smoker presented acutely with a two week history of left-sided odynophagia associated with haemoptysis. His past medical history was insignificant.
On examination, the patient had an enlarged left tonsil with an ulcerated, exophytic lesion. There was no palpable neck lymphadenopathy, and all inflammatory markers were within the normal range.
He was commenced on antibiotics; however, malignancy was suspected.
The patient underwent left tonsillectomy. Intra-operatively, a firm mass was found on the left tonsil, with no clinical invasion of immediate structures. The left tonsil was resected and sent for histological analysis. Endoscopy of the pharynx and larynx was normal.
A subsequent magnetic resonance imaging scan of the neck did not show any associated lymphadenopathy or extension of the tumour outside the tonsil (Figures 1 and 2), and a computed tomography (CT) scan of the mediastinum, abdomen and pelvis was normal.
Fig. 1 Axial, T1-weighted, post-gadolinium magnetic resonance imaging scan taken after tonsillectomy. There is swelling and enhancement of the left tonsillar bed and lateral oropharyngeal wall, extending into the parapharyngeal space and medial pterygoid muscle. A = anterior; R = right; L = left; P = posterior
Fig. 2 Axial short T1 inversion recovery (STIR) magnetic resonance imaging scan taken after tonsillectomy. There is swelling and oedema of the left tonsillar bed and lateral oropharyngeal wall, extending into the parapharyngeal space and medial pterygoid muscle. A = anterior; R = right; L = left; P = posterior
Macroscopically, the resected tonsil measured 30 × 25 × 20 mm with focal mucosal ulceration. On sectioning, the tonsillar parenchyma was found to be almost completely replaced by a firm, pale tumour measuring 25 mm in maximum dimension. The entire tonsil was sectioned and processed.
Microscopic examination showed the specimen to consist mainly of interwoven bundles of spindle cells (Figure 3) with eosinophilic cytoplasm, nuclear pleomorphism and a high mitotic rate, including atypical mitoses (Figure 4). The more superficial tissue was formed by polygonal cells with pleomorphic nuclei and abundant eosinophilic cytoplasm. The overlying squamous epithelium was extensively ulcerated.
Fig. 3 Low power photomicrograph showing interlacing bundles of spindle cells with mitotic figures. (H&E; ×10)
Fig. 4 High power photomicrograph showing an atypical mitotic figure within a spindle cell. (H&E; ×40)
Extensive immunocytochemical analysis was performed, with strong positivity for smooth muscle actin, desmin and vimentin, focal expression of epithelial membrane antigen, and focal nuclear expression of myogenin. There was no expression of cytokeratins (i.e. MNF116, CAM 5.2, CK7, AE1 and AE3), p63, E-cadherin, BCl2, ALK-1, melanocytic markers (i.e. HMB45 and S-100), endothelial markers (i.e. cluster of differentiation 31 and 34 glycoproteins), factor 13a, CD117 or PGP 9.5. The surface squamous epithelium did not show any dysplasia, and the neoplasm did not arise from the squamous epithelium at any point. No conventional squamous cell carcinoma (SCC) was identified in any of the tissue planes examined. Since all cytokeratin markers were consistently negative, epithelial membrane antigen showed very focal immunoreactivity, myogenin showed focal nuclear expression, and smooth muscle actin, desmin and vimentin showed marked, extensive positivity, the appearances were those of a high grade spindle cell sarcoma, with an immunocytochemical pattern favouring a diagnosis of high grade leiomyosarcoma.
Post-operatively, the patient was treated with a course of radical radiotherapy.
At 18 months, although he was clinically well, a subsequent CT scan of the chest revealed pulmonary metastases. The patient was offered chemotherapy but refused further treatment.
Discussion
Leiomyosarcomas are malignant tumours originating from smooth muscle cells and myoepithelial cells of salivary glands.Reference Ulrich, Feiz-Erfan, Spetzler, Isaacs, Hott and Nakaji3 Within the head and neck, these cells are mainly found in the walls of blood vessels and in the erector pili of the skin.Reference Tommerup, Mogensen and Nielsen7 The first reported case in the English language literature was in a 34-year-old patient who presented with a retromolar leiomyosarcoma.Reference Geever, Ackerman, Dublin and Stout8
Such tumours account for approximately 7 per cent of all soft tissue sarcomas and are most commonly seen in the gastrointestinal tract, uterus and retroperitoneum. They are extremely rare within the head and neck, where they usually arise in the skin, larynx, cervical oesophagus and sinonasal tract.Reference Ulrich, Feiz-Erfan, Spetzler, Isaacs, Hott and Nakaji3, Reference Ramkrishnan, Said and Kingdom4
Factors associated with an increased risk of leiomyosarcoma include previous irradiation and immunosuppression (particularly due to human immunodeficiency virus).Reference Sedghizadeh, Angiero, Allen, Kalmar, Rawal and Albright9,Reference Mbulaiteye, Prakin and Rabkin10 Associations have also been reported with Epstein–Barr virus infection and with a number of syndromes, including retinoblastoma, Gardner's syndrome and Recklinghausen's neurofibromatosis.Reference Maronio, Bertino, Mariuzzi, Berhamin-Bracale, Lombardo and Beltrami5
The clinical features of leiomyosarcoma are dependent on the site. Very few cases have been described in the pharynx, although hypopharyngeal lesions have been reported.Reference Tommerup, Mogensen and Nielsen7, Reference Fuller, Van Vliet, Lillie and Devine11, Reference Mankodi, Shah, Kanvinde and Joshi12 One patient presented with pyrexia of unknown origin, another with dysphagia and hoarseness.Reference Mankodi, Shah, Kanvinde and Joshi12 Another patient with tumour arising from the posterior pharyngeal wall presented with symptoms of dysphagia and hypernasal speech.Reference Glover and Park13 Two further cases of pharyngeal leiomyosarcoma have been described, but their exact site was unknown.Reference Montgomery, Golbulum and Fisher14, Reference Lajer, Daugaard, Hansen, Kirkegaard, Holmgaard and Christensen15
The differential diagnosis of leiomyosarcoma includes leiomyoma, malignant melanoma, spindle cell SCC and sarcoma. Diagnosing leiomyosarcoma based on microscopy alone can be difficult, and immunohistochemical and ultrastructural investigation may be required.Reference Maronio, Bertino, Mariuzzi, Berhamin-Bracale, Lombardo and Beltrami5, Reference Montgomery, Golbulum and Fisher14
In particular, spindle cell SCC can masquerade as leiomyosarcoma, as the conventional element of the SCC can be elusive and the spindle cell element can show striking morphological and immunohistochemical differentiation into sarcoma. Spindle cell SCC is usually a polypoid, mucosa-based tumour, and extensive sampling may be required to demonstrate an in situ or obvious epithelial infiltrating element. The epithelial component may show only focal cytokeratin positivity, although no immunoreactivity with desmin is noted.
The cell morphology of melanomas ranges from spindled to epithelioid, with prominent nucleoli. Pigment may or may not be present in the cytoplasm. However, these cells will be immunoreactive with at least one melanocytic marker, either S100 or HMB45.
Sarcomas (other than leiomyosarcoma) include myofibrosarcoma, fibrosarcoma, synovial sarcoma and malignant nerve sheath tumours. Myofibrosarcomas have tapered (rather than blunt-ended) nuclei and indistinct cell margins, and are immunoreactive for smooth muscle actin and (rather less frequently) for desmin. Fibrosarcomas have a sweeping fascicular arrangement with or without a herringbone pattern, they lack more than very focal muscle marker positivity, and they do not express S100 or epithelial markers. Synovial sarcomas have ovoid, smaller, rather uniform nuclei and scattered positivity for epithelial markers and BC12. Malignant peripheral nerve sheath tumours have serpentine nuclei and focal S100 positivity.
Our patient's tumour had an immunohistochemical profile characteristic of smooth muscle differentiation, with expression of smooth muscle actin and desmin. Immunoreactivity for cytokeratins was not detected, despite using a large panel of epithelial markers, except for very focal epithelial membrane antigen positivity, which can occur in leiomyosarcoma. No immunoreactivity was noted with S100, HMB45, BCL2 or ALK-1, thereby excluding melanoma, synovial sarcoma and myofibroblastic sarcoma. The surgical specimen was processed in its entirety, and there was no epithelial differentiation or dysplasia of the overlying squamous epithelium, which was ulcerated. Despite the various differential diagnoses to be considered in the case of a malignant spindle cell lesion, the findings for this tonsillar neoplasm were morphologically those of leiomyosarcoma. Moreover, extensive immunohistochemical staining was performed to establish that the neoplasm was a leiomyosarcoma; the findings of this staining excluded the presence of a carcinoma, melanoma or other type of sarcoma.
Contrary to previously reported pharyngeal leiomyosarcoma cases, which presented with chronic symptoms, our patient presented acutely with a two week history of odynophagia and haemoptysis. He underwent surgical resection followed by adjuvant radiotherapy; based on the current, limited literature, this would seem to be the treatment of choice. Certainly, for low grade tumours, complete surgical resection is considered to be the most effective treatment, although all treatment modalities have shown poor results when the lesion is high grade.Reference Ramkrishnan, Said and Kingdom4 Radiotherapy is frequently used as an adjuvant, as chemotherapy is considered to be less effective.Reference Ulrich, Feiz-Erfan, Spetzler, Isaacs, Hott and Nakaji3, Reference Goda, Saravanan, Vashistha, Kumar and Gupta16
• Leiomyosarcomas are rare within the head and neck
• This is the first reported case in the English language literature of leiomyosarcoma of the tonsil
• Leiomyosarcomas of the head and neck have a poor prognosis
The behaviour of smooth muscle tumours is dependent of their site of origin, and can be unpredictable.Reference Montgomery, Golbulum and Fisher14, Reference Dry, Jorgensen and Fletcher17 In the head and neck, leiomyosarcomas have been found to be aggressive tumours with a poor prognosis, with a five-year survival rate of 20 per cent.Reference Ulrich, Feiz-Erfan, Spetzler, Isaacs, Hott and Nakaji3 Metastatic spread is common.Reference Ulrich, Feiz-Erfan, Spetzler, Isaacs, Hott and Nakaji3, Reference Montgomery, Golbulum and Fisher14 Leiomyosarcomas presenting within the oral cavity typically show a more aggressive pattern, with higher rates of local recurrence and metastasis.Reference Dry, Jorgensen and Fletcher17 In a series of 13 patients with leiomyosarcoma in the head and neck, 27 per cent suffered recurrence within six to 24 months, and 55 per cent eventually developed regional or distant metastases.Reference Montgomery, Golbulum and Fisher14 Indeed, 34 per cent of leiomyosarcoma cases have evidence of distant metastasis at the time of presentation.Reference Pfeiffer, Boedeker, Ridder, Maier and Kayser1
To our knowledge, our patient represents the first case of leiomyosarcoma of the tonsil to be reported in the English language literature. The patient presented acutely, and was treated with complete surgical excision and adjuvant radiotherapy. This case highlights the natural progression and prognosis of such tumours, and the treatment modalities available.
