Sinonasal Neuroendocrine Neoplasms: Histopathologic Differentiation and Treatment Outcomes

Objectives: Sinonasal cancers of neuroendocrine origin are a rare group of malignancies that exhibit varying degrees of aggressive behavior; thus, presenting significant treatment challenges. They often show poorly differentiated morphology sharing several overlapping features, which makes their distinction from other poorly differentiated malignancies of the sinonasal tract difficult. A correct diagnosis is imperative for treatment and prognosis. The objective of this study was to report our experience with these malignancies and present a review of current literature with the emphasis on differential diagnosis, evaluation and treatment strategies.

Methods: Following IRB approval, the records of patients with biopsy-proven sinonasal malignancies at our institution were reviewed over a 5-year period (April 2010 to April of 2015). We identified 14 Esthesioneuroblasomas (ENB), 8 Sinonasal Undifferentiated Carcinomas (SNUC) and one Sinonasal Neuroendocrine Cancer (SNEC) case in 7 women and 16 men. Records were analyzed with regard to histopathologic diagnosis, treatment modalities, and outcomes.

Results: Thirteen patients with ENB presented with Kadish stages ranging from A to D (2/14 Kadish A, 4/14 Kadish B, 6/14 Kadish C and 1/14 Kadish D), or Dulguerov/UCLA staging from T1 to T3. One ENB patient was initially treated at another institution with no information about the initial tumor stage. Low-grade ENB was found in 9/14 (Hyam’s I-II) cases; whereas, 5/14 were high-grade (Hyam’s III) lesions. Patients with SNUC presented at advanced stages T4a-T4b by AJCC 7th TNM staging system, with assigned Kadish C-D stage (6/8 Kadish C stage and 2/8 Kadish D). The SNEC case was a poorly differentiated non-small cell type T4a tumor. At the time of diagnosis, two patients with ENB and two with SNUC had cervical node metastases. There were no distant metastases at the time of diagnosis.

In patients diagnosed prior to April of 2013 (11 of ENBs, 4 of SNUCs), the 2-year survival rates were 81% (9/11) for ENB and 75% (¾) for SNUC, however in one of the SNUC cases the final status was updated to “dead of disease” 2 months after 2-year cutoff. Four cases of recurrence (regional or distant) were noted (3 ENB and 1 SNUC). The SNEC patient succumbed to radiation treatment complications 21 months after the treatment. One ENB and three SNUC specimens required second pathologic consultation due to diagnostic challenges. Histopathologic markers aided in final diagnosis but had variable specificity.

Conclusions: Overlapping histopathologic features in poorly differentiated neuroendocrine sinonasal cancers continue to present a diagnostic challenge. Correct diagnosis is crucial for appropriate treatment and prognosis. Immunohistochemical markers are not specific, but serve as a useful adjunct to histologic evaluation of these malignancies. Individualized assessment and treatment strategies that take into account tumor stage, grade, and histopathologic characteristics can improve the accuracy of the initial assessment and treatment outcomes of sinonasal neuroendocrine malignancies.

Fig. 1 Coronal MRI of ENB, SNUC and SNEC Cases

Table 1

Table 2