Differential Diagnosis for Sinonasal Tumors

BACKGROUND

Malignant neoplasms arising in the nasal cavity and paranasal sinuses (sinonasal malignancies) are rare and comprise %3C;1% of all malignancies1 and only 3% of malignancies involving the upper aerodigestive tract.2

One such area is the “small round blue cell” tumor category. This group of tumors encompasses a wide diversity of both benign and malignant neoplasms. The separation and distinction between tumors is critical as some are managed by conservative medical therapy, others by local surgery, a different group by primarily radiation, some by chemotherapy only, whereas others are managed by exenterative surgery and multimodality therapies.

Here, we present two cases of small blue round cell tumors of the sinonasal tract, along with their management.

CASE DESCRIPTION

DISCUSSION

The differential diagnosis for small round cell tumors in the sinonasal tract is diverse and a thorough approach should be taken before rendering a diagnosis. Small tissue samples, with limitations of tumor volume, lack of architectural context, and a non-specific gross description, often make it difficult to reach a diagnosis. The pathologist may need to perform ancillary studies, including a broad panel of immunohistochemical stains and molecular studies.3

Ewing’s sarcoma/PNET is a closely related family of small round cell sarcomas with varying degrees of neuroectodermal differentiation. This was first described by pathologist James Ewing in 1921.4

Two clinical types of ES can be defined. The classical skeletal type may appear in any bone of the body; most frequently in long bones (35%) and pelvis (24%). The extraskeletal ES/PNET type usually occurs in the lower extremities, paravertebral tissues, chest wall, retroperitoneum, and occasionally head and neck (2–7%).5

Fertillo described four cases of head and neck sites that were most likely of skeletal origin6 but there are only several reported cases of sinonasal ES.7 It usually affects those <20 years old and has its peak incidence between 10 and 15 years. There is a 1.5:1 male to female ratio for this tumor.^8,9

Histopathologically, the tumors show high cellularity arranged in a diffuse, easily identified with limited vascular stroma.¹⁰

Due to advances in the treatment of EFT in recent years, survival rates (for all sites) are reported to have improved and have reached up to 86% in patients with non-metastatic disease at initial presentation.¹¹ Those with metastases have poorer outcomes.¹¹ Approximately 12–38% had metastases at first presentation.^11,12 Approximately 32% of patients overall died of the disease in one study¹¹ and those with metastases had an overall survival of only 21% in another study.¹²

Tumors are managed with multimodality therapy consisting of surgical debridement, chemotherapy, and radiotherapy, but there is a risk of post-treatment sarcoma development. Poor prognosis may be related to p53 aberrations.¹³

Rhabdomyosarcoma is a rare tumor that typically affects children and adolescents, with an annual incidence of 4.3 cases per 1 million population aged <20 years, with a peak incidence between ages 3 and 5 years and a second, smaller peak in adolescence, after which the incidence drops significantly with increasing age.¹⁴

Rhabdomyosarcoma arises in the head and the neck region in 40% of the cases. It commonly metastasizes to the lung and cervical lymph nodes. Patients’ prognosis depends on the age of the patient, histologic and clinical stage, and the exact tumor location. In the head and neck region, RMS is generally found in 1 of 3 characteristic sites: parameningeal, meningeal, and orbital. Parameningeal locations are the most common and include the middle ear, nasal cavity, paranasal sinuses, nasopharynx, and infratemporal fossa.¹⁵

Histologically, fibrovascular septa separate the tumor into nests of small to medium round cells, which aggregate in the center, showing a clinging dilapidated appearance at the fibrous septa.¹⁰

Stepan et al. found that the most common treatment used was chemotherapy with radiation therapy, in 49.5% of patients. The second-most commonly used treatment was a combination of surgery, chemotherapy, and radiation therapy, used in 25.8% of patients. Few patients underwent surgery and either chemotherapy or radiation alone.¹⁶

The overall 5-year survival is 44%. For patients treated with chemotherapy and radiotherapy or chemotherapy, radiotherapy, and surgery, the 5-year survival is 60%, compared with 19% for patients treated with the other forms of therapy. Factors associated with poorer survival are the adult onset of disease, alveolar histology, and treatment with systemic chemotherapy for less than 1 year. Patients receiving chemotherapy for %3E;1 year have a 5-year survival of 82%, compared with 71% for those with <1 year of treatment. Improved survival is associated with a lower incidence of distant metastasis.¹⁷ Young patients (5-year survival 62.5%) tend to have a better prognosis.^18–20

In an undifferentiated tumor, showing a small round blue cell morphology, the mnemonic “MR SLEEP” is helpful, as it highlights a series of tumors that must be considered in the differential diagnosis: melanoma, mesenchymal chondrosarcoma, rhabdomyosarcoma, sinonasal undifferentiated carcinoma (SNUC), squamous cell carcinoma (including NUT carcinoma), small cell osteosarcoma, lymphoma, esthesioneuroblastoma (olfactory neuroblastoma), ES/PNET, pituitary adenoma, and plasmacytoma.¹⁰

CONCLUSION

Small round blue cell tumors should be kept in mind while dealing with undifferentiated masses of the sinonasal tract, especially in childhood a high degree of suspicion should be present. A thorough clinical and endoscopic examination along with imaging is a must for the complete evaluation of such patients. The most common symptoms of such patients are nasal obstruction and epistaxis. Although eye symptoms are not present in every case, a thorough neurological and ophthalmological examination should be done. Early diagnosis and treatment of such patients lead to prognostic improvement and less morbidity for the patient.

CLINICAL SIGNIFICANCE

Early diagnosis and proper management of the tumors effectively improve the treatment outcome and lead to lowering of mortality and morbidity for the patient, without exposing the patient to unnecessary investigations.

REFERENCES

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