Report of a Rare Case of Spindle Cell Ameloblastic Carcinoma and the Diagnostic Utility of Immunohistochemistry.

Ameloblastic carcinoma is a rare aggressive malignant epithelial odontogenic tumor. The spindle cell variant of ameloblastic carcinoma (SCAC) is exceedingly rare with 15 cases of SCAC having been reported. Therefore, because of the paucity of cases in literature related to SCAC, the biological behavior of the entity has not been well evaluated. Herein the authors report a case of incidentally diagnosed SCAC in a 20-year-old woman identified on imaging as part of the evaluation of a work-related facial injury. Histologically, the tumor had background of cystic ameloblastoma with areas of dense hypercellular spindle cells with short-to-long intersecting fascicles and occasional herringbone pattern intermixed with solid epithelial nests. Both the epithelial and spindle cells were positive for cytokeratin including cytokeratin 19, D2-40, and transducin-like enhancer of split proteins-1 immunohistochemical stains. The patient was followed for 18 months with no evidence of recurrence or metastasis. To the knowledge this is a first case of reporting D2-40 positivity in spindle ameloblastic carcinoma and this immunostain could be used as helpful marker to diagnose this entity.

Highly differentiated follicular carcinoma of ovary: Use of imprint cytology at intraoperative consultation.

Highly differentiated follicular carcinoma of ovary (HDFCO) is a rare entity known to arise in struma ovarii. Clinical presentation and radiological features mimic other cystic ovarian neoplasm. Thus, intraoperative diagnosis of this entity can be challenging. We hereby report a HDFCO case of a 52-year-old woman, who presented with significant abdominal bloating for 3 months. Imaging showed a 11.7 cm left adnexal-mixed cystic and solid mass, adhering to the bowel with ascites. The mass was examined intraoperatively and showed multilocular cysts filled with straw or red brown-colored gelatinous fluid. Microscopically, the tumor consisted of small and large follicles with proteinous material and bland-looking cuboidal cells, suspicious for struma ovarii or granulosa cell tumor with extensive cystic changes, while imprint cytology slides showed watery colloid with cracking artifact favoring the former. However, the adherence to the bowel suggested HDFCO, and prompted surgical staging. The histology of the ovarian mass in the permanent section resembled goiterous thyroid tissue with invasion of endocervical stroma, uterine wall and colonic serosa, and presence of tumor nodules in omentum leading to the diagnosis of HDFCO. Due to striking resemblance of HDFCO to benign thyroid goiter, searching for invasive and metastatic foci is crucial for correct diagnosis. In addition, intraoperative imprint cytology revealing colloid with cracking artifact is helpful for differentiating struma ovarii and/or HDFCO from other ovarian lesions.

Correlation of p16 Expression on Cancer and Stromal Cells With Clinicopathologic and Immunohistochemical Features of Lobular Breast Carcinoma.

BACKGROUND: Cancer-associated fibroblasts, play a central role in the tumor-stroma interaction and promote tumorigenesis. However, it is still unclear how these processes are regulated. The aim of this study is to investigate p16 expression in cancer and stromal cells of invasive lobular carcinoma (ILC). DESIGN: Clinicopathologic parameters and immunohistochemical stains for estrogen receptor (ER), progesterone receptor, E-cadherin, and human epidermal growth factor receptor 2 of 70 ILC cases were retrieved. In addition, immunohistochemical were performed for p53, p16, and cyclin D1. The p16 expression in cancer and stromal cells were correlated with different clinicopathologic parameters. RESULTS: Of the 70 cases, 8 cases were p16- cancer and stromal cells, 14 cases p16- cancer and p16+ stromal cells, 14 cases p16+ cancer and p16- stromal cells, and 34 cases p16+ cancer and stromal cells. Thirty-one of the 59 cases showed axillary lymph node metastases. Nodal involvement, recurrence, and metastasis of ILC with p16+ cancer cells and p16- stromal cells were more frequent compared with other groups. ILC with p16+ cancer and p16- stromal cells were frequently negative for ER, progesterone receptor, and cyclin D1, p53 positive and triple negative compared with other groups. There was no recurrence and metastasis in ILC with p16- cancer and p16+ stromal cells. ILC with p16+ cancer and stromal cells were significantly node negative and were positive for ER and cyclin D1 compared with other groups. CONCLUSIONS: ILC with p16+ cancer and p16- stromal cells were characterized by frequent nodal involvement, recurrence, and metastatic propensity. These results suggest that p16, has novel anticancer properties capable of suppressing cancer cell migration and invasion and pharmacologic restoration of p16 level in stromal fibroblasts may be exploited as therapeutic strategy to prevent nodal or distant metastasis.

Aberrant Cytokeratin 20 Reactivity in Epithelioid Malignant Mesothelioma: A Case Report.

Malignant mesothelioma is an uncommon neoplasm that should be distinguished from the more common pulmonary adenocarcinomas and other metastatic lesions. Although diagnosis is based on morphologic features, immunohistochemical stains such as Calretinin, WT-1, CK-5/6, D2-40, Ber-Ep4, and MOC-31 are routinely used. Other organ-specific immunohistochemical markers are used when metastases from unknown primary lesion is suspected clinically. Here, we report a case of pleural epithelioid malignant mesothelioma expressing CK20. A 68-year-old male presented to the Emergency Department with nonproductive cough and progressive shortness of breath. Chest x-ray showed a large left-sided pleural effusion. Metastasis from a gastrointestinal primary was clinically suspected. Cytopathologic examination of the pleural fluid demonstrated atypical cells singly and in clusters with round nuclei, prominent nucleoli, and dense cytoplasm. The cell block demonstrated single and clusters of atypical cells positive for calretinin, D2-40, WT-1, CK-5/6, and CK7. Ber-EP4, MOC-31, TTF-1, Napsin-A, and CDX-2 were negative. CK20 was diffusely positive. A diagnosis of atypical mesothelial proliferation with aberrant CK20 expression was made. A subsequent pleural biopsy demonstrated sheets of highly atypical cells that were diffusely and strongly positive for the mesothelial markers and CK20. Multiple studies have shown malignant mesotheliomas to lack CK20 reactivity. To our knowledge, this is the first case report of a diffuse and strong CK20-positive mesothelioma. Such aberrant expressions should be kept in mind when cases are histologically atypical or lack reactivity for multiple mesothelial markers, especially when a gastrointestinal primary malignancy is suspected.

Amyloidosis diagnosed in cytology specimen of pleural effusion: A case report.

Amyloidosis is a rare condition resulting from extracellular deposition of amyloid, a fibrillary material derived from various precursor proteins. Involvement of the pleura by amyloidosis is a rare but serious complication. Pleural amyloidosis is primarily diagnosed by identifying amyloid deposition by histology on pleural biopsy specimens. Hereby, we report a case of systemic amyloidosis where we were able to identify amyloid in a pleural effusion specimen sent for cytopathology evaluation. A 59-year-old male with newly diagnosed multiple myeloma and systemic amyloidosis underwent therapeutic thoracentesis. The H&E stained cell block sections revealed a single, less than one millimeter focus of waxy material surrounded by a rim of reactive mesothelial cells suspicious for amyloid deposit in a background of fibrin, lymphocytes, and reactive mesothelial cells. The focus stained salmon pink with Congo-red special stain and showed apple-green birefringence under polarized light. Our finding suggests that pleural involvement in patients with systemic amyloidosis can be identified on effusion specimens and avert the need for more invasive procedures like pleural or pulmonary parenchymal biopsies.

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

INTRODUCTION: 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. MATERIALS AND METHODS: During 1992 and 2014, FNA of five cases of CAGCT were recorded. RESULTS: The patient's age ranged from 28 to 62 years. One was bilateral and all cases involved right side of ovary. The size of tumor was 5.5 to 10 cm. FNA of the five CAGCT show similar cytologic features except one case. Four cases contained a background composed of histiocytic cells and debris material. The tumor cells were small with round to oval nuclei and fine chromatin pattern, inconspicuous nucleoli, scanty cytoplasm with rare intranuclear longitudinal grooves. Tumor cells were arranged in small groups as well as single cells were appreciated some of which were deprived of cytoplasm. Microfollicular or rosette pattern were vague, some of which contain amorphous material resembling Call-Exner bodies. In addition, two cases also showed prominent papillary component and one of which was misdiagnosed for serous papillary carcinoma. All five cases were surgically resected and CAGCT was confirmed. CONCLUSIONS: FNA of CAGCT of ovary can be a challenging diagnosis as classic cytologic features may not be present and can be confused with benign follicular cyst especially when the ultrasound study favor benign cystic lesion. Rarely this tumor may show prominent papillary component and can be confused for a more clinically aggressive tumor such as papillary serous carcinoma. Diagn. Cytopathol. 2016;44:461-465. © 2016 Wiley Periodicals, Inc.

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.

Cytomorphology and immunohistochemistry of a recurrent clear cell odontogenic carcinoma with molecular analysis: A case report with review of literature.

Clear cell odontogenic carcinoma (CCOC) is a rare, odontogenic tumor of the jaws with mandibular involvement usually present in sixth decade of life with female preponderance. It is classified as a malignant tumor of odontogenic origin in 2005 by the World Health Organization because of its aggressive and destructive growth capacity and potential to metastasize. It needs to be distinguished from other primary and metastatic clear cell tumors of the oral and maxillofacial region. Recently, CCOCs have been noted to harbor a Ewing sarcoma breakpoint region 1 gene RNA-binding protein 1 (EWSR1) and activating transcription factor (ATF) gene translocation. To date, cytologic features of only one case have been reported in the literature. We report an additional case of 55-year-old woman with enlarging mass in the left mandible. This report describes cytologic and immunohistochemical features of CCOC with positive EWSR1 gene rearrangements by fluorescence in situ hybridization (FISH). As diagnosis of CCOC is challenging on fine-needle aspiration, immunohistochemistry and FISH analysis are very useful diagnostic tool in clear cell lesions of mandible.

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.

Hematologic lesions in urine cytology.

INTRODUCTION: Bladder infiltration by leukemia or lymphoma is rare and can mimic benign processes such as follicular cystitis (FC). MATERIALS AND METHODS: Eight benign and malignant hematologic diseases encountered in urine cytology were retrospectively reviewed for clinical, radiographic, and cytologic findings. RESULTS: There were 2 cases of acute myeloid leukemia, 2 cases of diffuse large B-cell lymphoma, and 4 cases of FC. The most common presenting symptom was hematuria. Imaging findings included echogenic debris within the bladder or an adjacent soft tissue mass in acute myeloid leukemia cases and bladder wall thickening in diffuse large B-cell lymphoma cases. No FC cases had any imaging abnormalities. Cytologic material of the leukemia cases showed numerous myeloid blasts with markedly increased nuclear-to-cytoplasmic ratios, centrally located nuclei, inconspicuous nucleoli, nuclear indentations, and some irregular nuclear membranes. The background showed sparse urothelial cells and histiocytes. Both lymphoma cases showed a discohesive population of atypical large lymphoid cells with irregular nuclear borders and prominent nucleoli. The FC cases had a background lymphoid cell population with a maturation spectrum from small lymphocytes to large lymphoid cells (immunoblasts) and histiocytes including tingible body macrophages. Additionally, there were many mature squamous cells and reactive urothelial cells. CONCLUSIONS: Bladder leukemia, lymphoma, and FC are infrequently encountered on urine cytology. FC can be distinguished from a hematologic malignancy by the presence of a lymphocytic maturation spectrum and tingible body macrophages. Radiologic abnormalities are associated with malignant processes; however, discrete bladder masses are usually not identified.

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.

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.

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.

Use of cervical mucus to screen for gynecological malignancies: a pilot study.

High-grade malignancies are the leading cause of death from gynecological tumors. Unfortunately, no efficient screening method is available for these tumors. In this paper we report the results of a pilot study based on the frequency of TP53 mutations in these cancers. Mucus from the cervix of 32 hysterectomy specimens with no grossly visible cervical or serosal involvement were included in this study. TP53 exons 5-9 mutations were screened for mutations using single strand conformation polymorphism (SSCP). Immunostain for p53 protein was performed in all fallopian tubes and in a sample from the tumors that were identified prospectively. A total of 32 cases including 19 malignant, and 13 benign cases were included. P53 immunostain was positive in only 5 cases including 3 high grade malignant tumors and 2 precancerous lesions (serous tubal intraepithelial lesion or p53 signature) in the fallopian tubes. A TP53 mutation band pattern was detected by SSCP in 2/3 and 2/2 cases respectively. Twenty-seven cases were negative for p53 imunostain, 4 of which were positive for TP53 mutation by SSCP including 3 low-grade malignancies. The results of this study provide evidence that DNA from precursor lesions of high grade ovarian, fallopian tube and endometrial carcinomas can be detected in cervical mucus. Further studies using different markers, in preoperative setting and large scale screening studies will determine the utility of using cervical mucus to screen for gynecological malignancies.

Gallbladder carcinoma in a pregnant patient with Crohn's disease complicated with gallbladder involvement.

Primary gallbladder (GB) carcinoma and Crohn's disease (CD) of the GB are individually rare. We present a case of a pregnant woman with CD found to have GB involvement and primary GB carcinoma. A 34-year-old female at 6 wk gestation with a 21 year history of CD of uncertain extent presented with 3 mo of diarrhea, urgency and abdominal pain. During work-up, she was found to have elevated transaminases and an abnormal alkaline phosphatase. Imaging revealed two gallbladder polyps both greater than 1 cm in size. Resection and histological evaluation was consistent with Crohn's involvement of the GB, poorly differentiated adenocarcinoma of the GB with invasion through the muscularis propria and matted lymph nodes in the porta hepatis positive for metastatic carcinoma (stage pT2N1). Six cases of CD involving the GB, two cases of primary GB carcinoma in CD, and ten cases of cholangiocarcinoma in pregnancy have been published. This is the only case that describes all three factors. Common features in CD of the GB include acute cholecystitis, ileal involvement, and presence independent of active intestinal disease. Common features in CD patients with GB malignancy include younger age of detection, a long history of CD, extensive colonic and ileal involvement of disease, the absence of cholelithiasis, and pre-existing gallbladder disease (primary sclerosing cholangitis and gallbladder polyps). Pregnancy is specific to this case. The role of CD in the development of GB malignancy is not well understood nor is the contribution of pregnancy to the spread of disease. Chronic inflammation and immunosuppression compounded by hormonal influence is implicated.

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.

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.