Ihab Lamzabi

Predicting aggressive behavior in nonfunctioning pancreatic neuroendocrine tumors

PURPOSE The biologic potential of nonfunctioning pancreatic neuroendocrine tumors (PNETs) is highly variable and difficult to predict before resection. This study was conducted to identify clinical and pathologic factors associated with malignant behavior and death in patients diagnosed with PNETs. METHODS We used International Classification of Diseases 9th edition codes to identify patients who underwent pancreatectomy for PNETs from 1998 to 2011 in the databases of 4 institutions. Functioning PNETs were excluded. Multivariate regression Cox proportional models were constructed to identify clinical and pathologic factors associated with distant metastasis and survival. RESULTS The study included 128 patients-57 females and 71 males. The age (mean ± standard deviation) was 55 ± 14 years. The body mass index was 28 ± 5 kg/m(2). Eighty-nine (70%) patients presented with symptoms, and 39 (30%) had tumors discovered incidentally. The tumor size was 3.3 ± 2 cm with 56 (44%) of the tumors measuring ≤2 cm. Seventy-three (57%) patients had grade 1 histology tumors, 37 (29%) had grade 2, and 18 (14%) had grade 3. Peripancreatic lymph node involvement was present in 31 patients (24%), absent in 75 (59%), and unknown in 22 (17%). Distant metastasis occurred in 18 patients (14%). There were 12 deaths, including 1 perioperative, 8 disease related, and 3 of unknown cause. With a median follow-up of 33 months, the overall 5-year survival was 75%. Multivariate Cox regression analysis identified age >55 (hazard ratio [HR], 5.89; 95% confidence interval [CI], 1.64-20.58), grade 3 histology (HR, 6.08; 95% CI, 1.32-30.2), and distant metastasis (HR, 8.79; 95% CI, 2.67-28.9) as risk factors associated with death (P < .05). Gender, race, body mass index, clinical symptoms, lymphovascular and perineural invasion, and tumor size were not related to metastasis or survival (P > .05). Three patients with tumors ≤2 cm developed distant metastasis resulting in 2 disease-related deaths. CONCLUSION Age >55 years, grade 3 histology, and distant metastasis predict a greater risk of death from nonfunctioning PNETs. Resection or short-term surveillance should be considered regardless of tumor size.

Myocardial changes in a patient with anorexia nervosa: a case report and review of literature.

OBJECTIVES Anorexia nervosa (AN) is an eating disorder with high mortality and morbidity. Much of the mortality is related to cardiovascular complications manifesting with electrocardiogram abnormalities and morphologic abnormalities documented on ultrasound. However, gross and histologic abnormalities in the heart have been rarely described in association with this eating disorder. METHODS We present an autopsy case of an adult patient with AN. We describe the clinical presentation of this patient, as well as significant gross and histologic abnormalities of the heart, and discuss their implications. RESULTS At autopsy, the heart was small with mainly a small left ventricle. Histologically, we found endocardial and interstitial fibrosis, areas of myxoid material deposition with mast cells in the background, and increased cytoplasmic lipofuscin. CONCLUSIONS The gross findings in the heart correlate with the previously described anomalies on cardiac ultrasound of patients with AN. The fibrosis and myxoid material deposition might be a direct consequence of starvation and the mechanism of death in some patients with AN.

Comparison of tumor markers for predicting outcomes after resection of nonfunctioning pancreatic neuroendocrine tumors

BACKGROUND This study compares the predictability of 5 tumor markers for distant metastasis and mortality in pancreatic neuroendocrine tumors (PNETs). METHODS A total of 128 patients who underwent pancreatectomy for nonfunctioning PNETs between 1998 and 2011 were evaluated. Tumor specimens were stained via immunochemistry for cytoplasmic and nuclear survivin, cytokeratin 19 (CK19), c-KIT, and Ki67. Univariate and multivariate regression analyses and receiver operating characteristics curve were used to evaluate the predictive value of these markers. RESULTS A total of 116 tumors (91%) were positive for cytoplasmic survivin, 95 (74%) for nuclear survivin, 85 (66.4%) for CK19, 3 for c-KIT, and 41 (32%) for Ki67 >3%. Twelve (9%) tumors expressed none of the markers. Survivin, CK19, and c-KIT had no substantial effect on distant metastasis or mortality. Age >55 years, grade 3 histology, distant metastasis, and Ki67 >3% were associated with mortality (P < .05). A cut-off of Ki67 >3% was the best predictor (83%) of mortality with an area under the curve of 0.85. Ki67 >3% also predicted occurrence of distant metastases with odds ratio of 9.22 and 95% confidence interval of 1.55-54.55 (P < .015). CONCLUSION Of the 5 markers studied, only Ki67 >3% was greatly associated with distant metastasis and death. Survivin, CK19, and c-KIT had no prognostic value in nonfunctioning PNETs.

Blastomycosis of bone: a clinicopathologic study.

OBJECTIVES Blastomycosis osteomyelitis is a well-known but infrequently encountered complication of infection with the dimorphic mold, Blastomyces dermatitidis. Oftentimes, the diagnosis is unsuspected, resulting in a delay in making the diagnosis. The role of intraoperative consultation in making a rapid diagnosis has not been discussed previously. METHODS Retrospective chart review of clinicopathologic information was conducted from all cases of blastomycosis osteomyelitis and arthritis diagnosed at Rush University Medical Center between 2000 and 2010. RESULTS Fourteen cases of blastomycosis osteomyelitis and/or arthritis were identified, 12 of which clinically and radiologically presented as a bone tumor. The disease most commonly affected the lower extremities, particularly around the knee joint. Septic arthritis generally occurred secondary to osteomyelitis of the adjacent bone. Frozen section was performed in 10 cases, all of which were correctly diagnosed as granulomatous osteomyelitis. Two cases were culture negative, one of which showed many budding yeast forms typical of B dermatitidis on histology. CONCLUSION Blastomycosis osteomyelitis should be considered in the differential diagnosis of bone tumor, particularly when there is history of residence or travel in endemic areas. This disease can be correctly identified at frozen section, thus offering rapid diagnosis. There is an excellent correlation between morphologic and microbiologic studies.

Correlation of clinicopathologic parameters and immunohistochemical features of triple-negative invasive lobular carcinoma.

Purpose:Invasive lobular carcinoma (ILC) is a subtype of invasive breast carcinoma. With the advent of gene profiling, breast cancer has been classified into luminal A, luminal B, HER2-overexpressing, and triple-negative carcinoma (TNC). Several studies have described TNC (ER−, PR−, HER2−) as a surrogate for basal-like breast carcinoma. However, there is sparse literature on triple-negative lobular carcinoma (TNLC), as most of them show hormone receptor expression. The aim of this study was to investigate the correlation of clinicopathologic parameters of TNLC that has been demonstrated in invasive ductal carcinoma. Materials and Methods:Clinicopathologic parameters and immunohistochemical stains for ER, PR, E-cadherin, HER2, MIB1, and fluorescent in situ hybridization for HER2 of 255 ILC cases were retrieved. In addition, immunohistochemical analysis was performed for p53, c-kit, vimentin, p16, cyclinD1, and BCL2 on 78 cases where 12 were TNC cases and 66 were non-TNC cases. Results:Of the 255 ILC cases, 218 (85.5%) were classic and 37 (14.5%) were pleomorphic. Seventy-seven (30.1%) cases showed axillary lymph node metastasis. There were 14 of the 255 TNC cases (5.49%) that showed higher incidence in the elderly patients. Six of the 37 (16.21%) cases were pleomorphic and 8 of the 218 (3.7%) cases were classic. Positivity for vimentin was seen in 8 of the 12 cases (67.7%), CK 5 in 3 of the 12 (25%) cases, p16 in 11 of the 12 (91.6%) cases, p53 in 8 of the 12 (66.7%) cases, c-kit in 6 of the 12 (50%) cases, and cyclinD1 in 6 of the 12 cases (50%) indicating basal-like phenotype in 3 cases and nonbasal-like phenotype in 9 cases. There was no statistical significance in lymph node metastasis, tumor recurrence, and distant metastasis between TNC and non-TNC. Conclusions:TNLC showed distinct clinicopathologic features such as more frequently seen in the elderly, pleomorphic, larger tumor size, increased expression of vimentin, CK 5, p16, p53, and c-kit. Not all cases showed basal-like phenotype. TNLC is less frequently seen as compared with TNC in invasive ductal carcinoma.

Immunophenotype of myxopapillary ependymomas.

Myxopapillary ependymoma (MPE) is a slow-growing tumor occurring almost exclusively in the region of conus medullaris, cauda equina, and filum terminale. On microscopic examination, some of these tumors show solid sheets of cells with an epithelioid morphology mimicking a metastatic carcinoma. Several immunohistochemical studies addressed this issue with discordant results. We report the immunohistochemical findings of 9 additional cases of MPE. From 2004 to 2011, a total of 9 cases of MPE were recorded in our surgical pathology files. The histologic material and clinical data were reviewed for each case. There were 6 female and 3 male patients. The ages ranged from 15 to 58 years (mean, 31 y). Eight cases were intradural, lumbosacral (L1-S1), and 1 case was located in the sacrum. All tumors expressed CD99 and GFAP (100%). Eight tumors were positive for CD56 (89%). All tumors (100%) expressed focally CKAE1/AE3. One tumor (11%) was focally positive for CK8/18 and CK7. D2-40 was focally positive in 1 case (11%). PLAP and AFP were both negative in all cases. Synaptophysin was focally positive in 1 case. NSE was positive in all cases. All tumors were negative for CK5/6, CK20, E-cadherin, and TTF-1. Our study shows that the vast majority of MPE are positive for CD99, CD56, and GFAP. In selective cases, especially when the material obtained for pathologic evaluation is scanty and the tumor displays epithelioid appearance, the diagnosis may be challenging owing to cytokeratin positivity suggesting metastatic carcinoma. However, the clinical and radiologic features in addition to the positivity for GFAP should prompt pathologists to consider MPE in the differential diagnosis of such cases. Interestingly, we found that MPE are positive for NSE, which suggests a neuroglial differentiation.

Androgen receptor expression in vascular neoplasms of the breast.

Introduction:Androgen receptors (AR) have been reported to be present in normal breast tissue and breast carcinomas. The following study was undertaken to assess the expression of AR in vascular neoplasms of the breast. Materials and Methods:All patients with histologically diagnosed hemangioma, angiolipoma, atypical vascular proliferation, and angiosarcoma of the breast were retrieved from the clinical and pathology database at Rush University Medical Center. The slides stained with hematoxylin and eosin were reviewed and immunohistochemical staining for AR (Dako; clone AR441) was performed on paraffin-embedded tissue. Any amount of nuclear staining was considered positive and the intensity of staining was graded as 1+ to 3+. An estimate of the percentage of tumor and stromal cells staining was made. Results:There were a total of 36 cases, 10 hemangiomas, 20 angiolipomas, 2 atypical vascular proliferation, and 4 angiosarcomas. The male to female ratio was 1:4.1. The average age at presentation for men was 45 years and for women was 56.9 years. Anti-AR expression was present in stromal and adipocyte nuclei of the angiolipomas and stromal cells of hemangiomas and angiosarcomas. Interestingly, normal duct epithelium of the breast was positive in 7 of the 29 women and none in men. Androgen expression was present in 62.5% of the hemangiomas, 55% of the angiolipomas, and 50% of the angiosarcomas. The majority of tumors showed a low-intensity nuclear expression of androgens, with 1+ intensity in 13 cases and 2+ intensity seen in 2 cases, and only 1 case of angiolipoma showed 3+ expression. All positive cases of angiolipoma (55%) showed AR in adipocytes and stromal cells. Conclusions:Vascular neoplasms are uncommon tumors in breast and majority of them are benign. Androgen expression is present in >50% of benign vascular neoplasms. Stromal cells and adipocytes typically express AR only in angiolipomas, suggesting a role of androgens in pathogenesis and growth of this neoplasm.

Fine needle aspiration cytology of cystic primary adult granulosa cell tumor of the ovary: Potential diagnostic pitfalls with other cystic ovarian lesions.

Fine needle aspiration(FNA) of cystic adult granulosa cell tumors(CAGCT) has been sporadically reported in the literature. We undertook a retrospective study to further elucidate the cytologic features on FNA material in order to avoid possible misinterpretation with other primary tumors of ovary.

Prognostic Value of Coexisting Lobular Carcinoma In Situ With Invasive Lobular Carcinoma

Aims and Objectives:Recent studies show that lobular carcinoma in situ (LCIS) and invasive lobular carcinoma (ILC) share similar genetic molecular biology. There are increasing concerns regarding the biological significance of LCIS. The aim of this study is to investigate whether the presence of coexisting LCIS in ILC affects tumor biology and behavior and to correlate it with other clinicopathologic parameters. Materials and Methods:In this study, 254 cases of ILC were included. Clinicopathologic parameters and immunohistochemical stains for estrogen receptor (ER), progesterone receptor (PR), E-cadherin, human epidermal growth factor receptor (HER2), and MIB-1 of 254 ILC cases were retrieved. The patient with ILC and coexisting LCIS were compared with pure ILC cases with respect to different clinicopathologic parameters. Results:Of the 254 cases, 107 cases were pure ILC and 147 cases were ILC with coexisting LCIS. Seventy-six (76/184, 41.32%) cases showed axillary lymph node metastases. Lymph node metastasis was absent in 108 cases, micrometastasis was present in 5 cases, and stage N1, N2, N3 in 51, 5, and 15 cases, respectively. Nodal involvement, locoregional and distant recurrence of ILC with LCIS were less frequent compared with ILC without LCIS with P-value of 0.034 and 0.007, respectively. The presence of coexisting LCIS in ILC predicted higher disease-free survival (DFS) compared with pure ILC (P=0.034, log-rank test). When divided into different strata, ER-positive ILC cases with associated LCIS cases showed better DFS than ER-positive pure ILC cases (P=0.021, log-rank test). Similarly, ILC cases with LCIS in patient less than 50 years showed better DFS than the patient less than 50 years with pure ILC (P=0.045, log-rank test). Conclusions:In conclusion, ILC coexisting with lobular carcinoma in situ (ILC+LCIS) is characterized by less nodal involvement, lower locoregional, and distant recurrence and better DFS than pure ILC. When divided into different strata, ER-positive and less than 50-year groups with ILC+LCIS show even significant better DFS than pure ILC. These findings suggest that there is biological significance of coexisting LCIS in ILC and that this may have more effect on tumor aggressiveness in certain strata of ILC.

Colonic diffuse large B-cell lymphoma in a liver transplant patient with historically very low tacrolimus levels.

Posttransplant lymphoproliferative disorders (PTLDs) comprise a wide spectrum of hematologic malignancies that are found increasingly in orthotopic liver transplant (OLT) patients given the rising frequency of these surgeries and their long-term success. PTLDs are highly correlated with both the Epstein-Barr virus (EBV) infection and the degree of immunosuppression involved. Herein is reported a case of a 53-year-old male with successfully treated hepatitis C virus genotype 4 and hepatocellular carcinoma who underwent OLT and developed symptoms of weakness and poor appetite 4 years later while on tacrolimus 3 mg b.i.d. with historically very low plasma levels. He was found to be anemic and colonoscopy revealed a 4.5 cm cecal diffuse large B-cell lymphoma (DLBCL). Further workup revealed mesenteric lymph node enlargement consistent and nodal DLBCL dissemination. He was treated with cyclophosphamide-hydroxyldaunorubicin-oncovin-prednisone-rituximab (CHOP-R) chemotherapy and his tacrolimus dose was lowered. Additionally, he manifested PTLD-associated cryoglobulinemia leading to acute kidney injury. After a prolonged hospitalization he was discharged with close followup.