Faculty Bibliography

We report 3 new patients with sinonasal renal cell-like adenocarcinoma (SNRCLA). One case submitted in consultation demonstrated robust carbonic anhydrase IX (CA-IX) expression, leading us to a broader inquiry of CA-IX and carbonic anhydrase II (CA-II) expression in other SNRCLA, Schneiderian tissues, and histologic mimickers. Robust cytoplasmic and membranous CA-IX expression is demonstrated in 6 of 7 SNRCLAs; CA-II expression was demonstrated in 2 of 5 cases. Robust, diffuse CA-II expression is demonstrated throughout sinonasal seromucinous glands in all 10 normal Schneiderian samples. CA-IX is also expressed in all normal sinonasal samples, albeit focally. The closest salivary mimic to SNRCLA is hyalinizing salivary clear cell carcinoma; only focal CA-IX expression was demonstrated in 1 of 2 cases studied. Carbonic anhydrase expression in Schneiderian tissue speaks to its role in regulating the ion concentration of sinonasal secretions and may also explain the origin of this rare tumor.

Over the past 40 years, the incidence of neuroendocrine tumors (NETs) has been increasing. Distal small bowel (i.e., midgut) NETs most often cause carcinoid syndrome manifested as cutaneous flushing, diarrhea, bronchial constriction, and cardiac involvement. Carcinoid abdominal crisis occurs when submucosal tumors impede the vascular supply to the gut leading to mesenteric ischemia and worsening abdominal pain. Here, we report the case of a young woman with progressively worsening abdominal pain. J. Surg. Oncol. 2014 110:348-351. (c) 2014 Wiley Periodicals, Inc.

OBJECTIVE: Chronic blood transfusion therapy reduces clinical events in children with sickle cell anemia but increases risk for an iron-related liver injury. Liver biopsy is the gold standard technique for quantifying liver iron content (LIC) and evaluating liver pathology. Ferritin, liver enzymes, and R2* magnetic resonance imaging of the liver are obtained as surrogate markers. In this study we compared surrogate markers with the gold standard, liver biopsy, in assessing liver histology. METHODS: We conducted a retrospective review of 259 liver biopsies in 109 children with sickle cell anemia on chronic transfusion therapy and chelation therapy during a 9-year period at a single center. Liver pathology was compared with LIC, ferritin, and alanine aminotransferase. RESULTS: Ferritin correlates with LIC (r = 0.74, P < 0.001), although there is a broad range of ferritin values for a given LIC. Furthermore, patients with a high LIC (>/=7 mg Fe/g dry weight) demonstrated significantly higher ferritin as compared to the patients with lower LIC <7 (P < 0.001). Periportal/portal inflammation also showed a significant relation. There was no significance when comparing ferritin and lobular inflammation or ferritin and alanine aminotransferase. When evaluating LIC in relation to fibrosis, the present study revealed that there was only a significant correlation with severe fibrosis (F = 36, P < 0.001). CONCLUSIONS: The results suggest that although correlations exist among ferritin and LIC and severe fibrosis and LIC, caution should be taken when they are used in isolation. Liver biopsy provides important pathologic information that cannot be obtained through surrogate markers.

The Risk Model is a validated outcome predictor for patients with head and neck squamous cell carcinoma (Brandwein-Gensler et al. in Am J Surg Pathol 20:167-178, 2005; Am J Surg Pathol 34:676-688, 2010). This model may potentially shift treatment paradigms for patients with low-stage cancers, as current protocols dictate that they might receive only primary surgery. Here we test the hypothesis that the Risk Model has added prognostic value for low-stage oral cavity squamous cell carcinoma (OCSCC) patients. 299 patients with Stage I/II OCSCC were characterized according to the Risk Model (Brandwein-Gensler et al. in Am J Surg Pathol 20:167-178, 2005; Am J Surg Pathol 34:676-688, 2010). Cumulative incidence and competing risk analysis were performed for locoregional recurrence (LRR) and disease-specific survival (DSS). Receiver operating characteristic analyses were performed for worst pattern of invasion (WPOI) and the risk categories. 292 patients were analyzed; 30 T1N0 patients (17 %) and 26 T2N0 patients (23 %) developed LRR. Disease-specific mortality occurred in 9 T1N0 patients (6 %) and 9 T2N0 patients (10 %). On multivariable analysis, the Risk Model was significantly predictive of LRR (p = 0.0012, HR 2.41, 95 % CI 1.42, 4.11) and DSS (p = 0.0005, HR 9.16, 95 % CI 2.65, 31.66) adjusted for potential confounders. WPOI alone was also significantly predictive for LRR adjusted for potential confounders with a cut-point of either WPOI-4 (p = 0.0029, HR 3.63, 95 % CI 1.56, 8.47) or WPOI-5 (p = 0.0008, HR 2.55, 95 % CI 1.48, 4.41) and for DSS (cut point WPOI-5, p = 0.0001, HR 6.34, 95 % CI 2.50, 16.09). Given a WPOI-5, the probability of developing locoregional recurrence is 42 %. Given a high-risk classification for a combination of features other than WPOI-5, the probability of developing locoregional recurrence is 32 %. The Risk Model is the first validated model that is significantly predictive for the important niche group of low-stage OCSCC patients.

Mucoepidermoid carcinoma (MEC) is a relatively common salivary tumor with varying potential for aggressive behavior. Mucoepidermoid carcinoma grading has evolved from descriptive two-tiered schemata to more objective three-tiered systems. In 2001, we published a grading system Brandwein et al. in Am J Surg Pathol 25:835-845, (2001) which modified the prevailing criteria of Auclair et al. in Cancer 69:2021-2030 (1992), and included additional features of aggressive MEC. Here we seek to validate our modified grading system in a new multicenter cohort. The retrospective cohort consisted of 76 patients with confirmed MEC and known outcome data. The resection specimens were reviewed and uniformly graded according to our modified criteria Brandwein et al. in Am J Surg Pathol 25:835-845 (2001), and the Auclair criteria Auclair et al. in Cancer 69:2021-2030, (1992), Goode et al. in Cancer 82:1217-1224, (1998). Case distribution was as follows: Montefiore Medical Center: 41 (1977-2009), University of Alabama at Birmingham: 21 (1999-2010), and Rhode Island Hospital: 14, (1995-2011). Patient age ranged from 7 to 81 years (mean 51 years). The female to male ratio was 3:1. The most commonly involved sites were: parotid: n = 39 (51%), palate: n = 10 (13%), retromolar trigone: n = 6 (8%), buccal: n = 5 (7%), and submandibular gland: n = 5 (7%). The modified criteria upgraded 41% MEC; 20/25 MEC from AFIP Grade 1 to Grade 2 and 5/25 from AFIP grade 1 to grade 3. Eleven patients had positive lymph nodes; the AFIP MEC grade for cases were: grade 1-3/11, Grade 2-1/11, and grade 3-7/11; the modified grading criteria distribution for these cases were Grade 1: 0/11, grade 2: 1/11, and grade 3: 10/11. Nine patients developed disease progression after definitive treatment. High-stage and positive lymph node status were significantly associated with disease progression (p = 0.0003 and p < 0.0001, respectively). For the nine patients with disease progression, the modified grading schema classified eight MEC as grade 3 and one as grade 2. By comparison, the AFIP grading schema classified three of these MEC as grade 1, and the remaining six as grade 3. Despite the fact that this multicenter retrospective study accrued 76 patients with outcome, the predictive performance of the two grading schema could not be compared due to the few patients who experienced disease progression and were also reclassified with respect to grade (n = 3).

Intraosseous hibernoma is a rare benign bone tumor, with only 3 cases reported in English literature. In this report, we describe a 50-year-old woman with a history of stage IIB breast cancer and posterolateral right hip pain. Imaging studies showed a sclerotic lesion in the right ilium, which was biopsied and showed mildly thickened bone trabeculae and multivacuolated brown fat cells replacing the normal white fat and hematopoietic elements, diagnostic of intraosseous hibernoma.

Granulosa cell tumors are classified as juvenile and adult types. They may be misinterpreted as a yolk sac tumor when they exhibit a "reticular" growth pattern and contain prominent mitotic activity. In this study, the authors performed immunohistochemical stains for SALL4 and steroidogenic factor-1 (SF-1) on 27 cases of yolk sac tumors and 24 granulosa cell tumors. Nuclear stains for both antibodies were considered as positive and the intensity of staining was graded as negative, weak, moderate, and strong. All the yolk sac tumors were positive for SALL4 (100%) with moderate to strong grade staining and negative for SF-1 (100%). In contrast, all the granulosa cell tumors were positive for SF-1 (85% moderate to strong grade staining and 15% weak staining) and negative for SALL4 (100%). The difference was significant (P < .01, Student's t test). This result indicates that these 2 markers could be used to distinguish these 2 tumors in a difficult situation.

Sclerosing epithelioid fibrosarcoma (SEF) is a distinctive variant of fibrosarcoma characterized by epithelioid tumor cells arranged in nests, cords, or sheets embedded within a sclerotic collagenous matrix. It is a relatively newly described malignant fibroblastic tumor, with only fewer than 100 cases reported in English literature. Most cases are located in the lower extremities and limb girdles. Here, we present a case of SEF of the pancreas in a 67-year-old white man and provide a review of literature to date, with emphasis on the differential diagnosis. To our knowledge, this is the first reported case of SEF involving the pancreas.