Nuclear expression of AFF2 C-terminus is a sensitive and specific ancillary marker for DEK::AFF2 carcinoma of the sinonasal tract.

DEK::AFF2 carcinoma of the sinonasal tract is an emerging entity. The tumor is typically characterized by papillary proliferation of non-keratinizing squamous epithelial cells with monotonous cytologic features, which may mimic other sinonasal tumors. The confirmation of this gene fusion has thus far relied solely on next-generation sequencing, fluorescence in situ hybridization (FISH), or reverse transcription polymerase chain reaction (RT-PCR). This current study aimed to validate an immunohistochemical assay for AFF2 C-terminus as an ancillary marker. We first analyzed publicly available RNA sequencing data of sinonasal tumors from the national center for biotechnology information (NCBI) sequence read archive and identified 3 DEK::AFF2 carcinomas out of 28 sinonasal tumors. The gene expression of AFF2 was significantly higher in the fusion-positive cases compared to the wild-type tumors (p < 0.001), while DEK was not. We then optimized an immunohistochemical assay with an anti-AFF2 C-terminus antibody for ancillary diagnosis. Seventeen DEK::AFF2 carcinomas, including 11 cases with predominantly low-grade morphology and one showing glandular differentiation, as well as 78 DEK FISH-negative sinonasal tumors were evaluated by AFF2 immunohistochemistry (IHC). Sixteen of the 17 DEK::AFF2 carcinomas showed nuclear AFF2 expression in ≥30% of tumor cells, including one decalcified case that failed FISH and RT-PCR confirmation. The one case that was negative for AFF2 IHC in the tumor cells also lacked expression in the internal positive control. It was thus considered a failure of the IHC rather than a truly negative case and was excluded from the statistical analysis. All DEK FISH-negative sinonasal tumors were negative for nuclear AFF2 expression. The nuclear expression of AFF2 IHC showed 100% sensitivity and specificity for DEK::AFF2 carcinoma. Accordingly, AFF2 IHC is a highly sensitive and specific ancillary marker that distinguishes DEK-AFF2 carcinoma from the other sinonasal tumors with overlapping morphological features and may be an especially useful alternative for decalcified specimens.

Rare Undiagnosed Primary Amyloidosis Unmasked During Surgical Treatment of Primary Hyperparathyroidism: A Case Report.

Primary amyloidosis (PA) is a protein deposition disorder that presents with localized or multisystemic disease. The incidence is low in the general public, ranging from three to eight cases per million, and with nonspecific presenting symptoms typically occurring later in life. Due to late presentation, substantial and irreversible damage has usually already occurred by the time of the diagnosis. However, if inadvertent diagnosis occurs before irreversible damage has taken place, as it did in the following case, some patients may benefit from the disease-arresting treatment. A 70-year-old female with a history of obstructive sleep apnea, hypertension, and arthritis presented with worsening dysphagia and biochemically confirmed primary hyperparathyroidism (PHPT). Further workup demonstrated multinodular goiter with compressive symptoms and substernal extension, osteopenia, and discrepant parathyroid localization on imaging. Intraoperatively, markedly difficult dissection and obliteration of tissue planes were encountered. Extensive, diffuse amyloid deposition in both the normal and pathologic parathyroid glands and thyroid tissue on surgical pathology leads to subsequent fibril typing by mass spectrometry and leads to the diagnostic of primary amyloid light-chain (AL) amyloidosis (PA; λ light chains). Subsequent workup for the underlying cause of the amyloid deposition revealed an immunoglobulin A monoclonal gammopathy of unknown significance. The surgical treatment of PHPT and compressive thyroid nodule unmasked an undiagnosed PA, allowing for early workup and monitoring of the progression of amyloidosis. The temporal comorbidity of PHPT and PA raises an interesting and, as yet, unanswered question regarding the pathophysiologic association between the two conditions.