Activity of the endo-beta-glucuronidase heparanase, capable of cleaving heparan sulfate (HS), is most often elevated in many types of tumors, associating with increased tumor metastasis and decreased patients’ survival. Heparanase is therefore considered to be a valid drug target, and heparanase inhibitors are being evaluated clinically in cancer patients. Heparanase 2 (Hpa2) is a close homolog of heparanase that gained very little attention, likely because it lacks HS-degrading activity typical of heparanase. The role of Hpa2 in cancer was not examined in detail. In head and neck cancer, high levels of Hpa2 are associated with decreased tumor cell dissemination to regional lymph nodes and prolonged patients’ survival, suggesting that Hpa2 functions to attenuate tumor growth. Here, we examined the role of Hpa2 in normal thyroid tissue and in benign thyroid tumor, non-metastatic, and metastatic papillary thyroid carcinoma (PTC) utilizing immunostaining in correlation with clinicopathological parameters. Interestingly, we found that Hpa2 staining intensity does not significantly change in the transition from normal thyroid gland to benign, non-metastatic, or metastatic thyroid carcinoma. Remarkably, we observed that in some biopsies, Hpa2 is accumulating on the membrane (envelop) of the nucleus and termed this cellular localization NM (nuclear membrane). Notably, NM localization of Hpa2 occurred primarily in metastatic PTC and was associated with an increased number of positive (metastatic) lymph nodes collected at surgery. These results describe for the first time unrecognized localization of Hpa2 to the nuclear membrane, implying that in PTC, Hpa2 functions to promote tumor metastasis.

Objective To examine associations of laboratory and imaging data with diagnostic parameters of necrotizing otitis externa (NOE) and its severity, and to compare between bacterial and fungal infections. Methods Records of patients diagnosed with NOE during 2010–2018 at the Department of Otolaryngology, Head and Neck Surgery were reviewed retrospectively for demographics; disease characteristics; and laboratory, scintigraphy, and imaging results. Results Of 48 patients with NOE, the mean age is 73±11.6 years; 32 (67%) were males; 83% had diabetes mellitus. Common pathogens were pseudomonas (49%) and fungi (33%). Sensitivities of the technetium-scan (SPECT ratio ≥1.5), temporal bone computed tomography (CT), and gallium-scan (SPECT ratio ≥1.3) were: 78.7%, 48.8%, and 31.4%, respectively. Gallium-scan results correlated positively with CT bone involvement (p=0.002) and hospital length of stay (p=0.0014). C-reactive protein (CRP) level correlated with hospital length of stay (p=0.028) and positive technetium-scan results (p=0.012). Fungal infection had a higher technetium SPECT ratio (2.16 vs. 1.77, p=0.04), gallium SPECT ratio (1.4 vs. 1.2, p=0.02), longer duration of systemic treatment (87.4 vs. 37.9 days, p=0.014), and longer hospital length of stay (31.6 vs. 15.2 days, p=0.004) compared to non-fungal infection. Eight (17%) patients had responded poorly to treatment. Fungal pathogens, facial nerve paresis, extra-auricular, and bilateral disease were more prevalent among the non-responders. Conclusion The technetium scan has higher sensitivity than temporal bone CT for diagnosing NOE. The gallium scan and CRP correlated well with hospital length of stay. A high rate of fungal infection was found, with significantly higher technetium and gallium SPECT ratios and worse outcome compared to bacterial infection. Fungal NOE remains therapeutically challenging.