Surg Pathol Research Articles

Abstract CN13-03: Next-generation stool DNA testing

Abstract CN13-03: Next-generation stool DNA testing

Identifying Patients with Atypical Ductal Hyperplasia Diagnosed at Core-Needle Biopsy Who Are at Low Risk of Malignancy

HomeRadiologyVol. 257, No. 3 PreviousNext CommunicationsLetters to the EditorIdentifying Patients with Atypical Ductal Hyperplasia Diagnosed at Core-Needle Biopsy Who Are at Low Risk of MalignancyConstance T. Albarracin*, Christopher V. Nguyen*, Gary J. Whitman†, Wei Weiang†, Nour Sneige* Constance T. Albarracin*, Christopher V. Nguyen*, Gary J. Whitman†, Wei Weiang†, Nour Sneige* Author AffiliationsDepartments of Pathology* and Diagnostic Radiology† University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030e-mail: [email protected]Constance T. Albarracin*Christopher V. Nguyen*Gary J. Whitman†Wei Weiang†Nour Sneige* Published Online:Dec 1 2010https://doi.org/10.1148/radiol.101253MoreSectionsFull textPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In References1 Kohr JR, Eby PR, Allison KHet al.. Risk of upgrade of atypical ductal hyperplasia after stereotactic breast biopsy: effects of number of foci and complete removal of calcifications. Radiology 2010;255(3):723–730. Link, Google Scholar2 Ely KA, Carter BA, Jensen RA, Simpson JF, Page DL. Core biopsy of the breast with atypical ductal hyperplasia: a probabilistic approach to reporting. Am J Surg Pathol 2001;25(8):1017–1021. Crossref, Medline, Google Scholar3 Forgeard C, Benchaib M, Guerin Net al.. Is surgical biopsy mandatory in case of atypical ductal hyperplasia on 11-gauge core needle biopsy? a retrospective study of 300 patients. Am J Surg 2008;196(3):339–345. Crossref, Medline, Google Scholar4 Nguyen C, Albarracin CT, Whitman G, Lopez A, Sneige N. Atypical ductal hyperplasia in directional vacuum-assisted biopsy of breast microcalcifications: considerations for surgical excision. Ann Surg Oncol [in press]. Google Scholar5 Sneige N, Lim SC, Whitman GJet al.. Atypical ductal hyperplasia diagnosis by directional vacuum-assisted stereotactic biopsy of breast microcalcifications: considerations for surgical excision. Am J Clin Pathol 2003;119(2):248–253. Crossref, Medline, Google Scholar6 Wagoner MJ, Laronga C, Acs G. Extent and histologic pattern of atypical ductal hyperplasia present on core needle biopsy specimens of the breast can predict ductal carcinoma in situ in subsequent excision. Am J Clin Pathol 2009;131(1):112–121. Crossref, Medline, Google ScholarArticle HistoryPublished online: Dec 2010Published in print: Dec 2010 FiguresReferencesRelatedDetailsCited ByComplex General Surgical Oncology: A Case-Based Approach - Volume 1VanceSohn2013Multidisciplinary Considerations in the Management of High-Risk Breast LesionsSavitriKrishnamurthy, ThereseBevers, HenryKuerer, Wei T.Yang2012 | American Journal of Roentgenology, Vol. 198, No. 2Definitive Diagnosis for High-Risk Breast Lesions Without Open Surgical Excision: The Intact Percutaneous Excision Trial (IPET)Pat W.Whitworth, Jean F.Simpson, William R.Poller, Steven M.Schonholz, John F.Turner, Rogsbert F.Phillips, Joel M.Johnson, F. DavidMcEachin2011 | Annals of Surgical Oncology, Vol. 18, No. 11Radiopaedia.orgRohitSharma, TheRadswiki2010Accompanying This ArticleErrataMar 1 2011RadiologyRecommended Articles Underestimation Rate at MR Imaging–guided Vacuum-assisted Breast Biopsy: A Multi-Institutional Retrospective Study of 1509 Breast BiopsiesRadiology2016Volume: 281Issue: 3pp. 708-719Ductal Carcinoma in Situ: State-of-the-Art ReviewRadiology2021Volume: 302Issue: 2pp. 246-255Growth Dynamics of Mammographic Calcifications: Differentiating Ductal Carcinoma in Situ from Benign Breast DiseaseRadiology2019Volume: 292Issue: 1pp. 77-83Digital Mammography Stereotactic Biopsy versus Digital Breast Tomosynthesis–guided Biopsy: Differences in Biopsy Targets, Pathologic Results, and Discordance RatesRadiology2020Volume: 294Issue: 3pp. 518-527High-Risk Breast Lesions: A Machine Learning Model to Predict Pathologic Upgrade and Reduce Unnecessary Surgical ExcisionRadiology2017Volume: 286Issue: 3pp. 810-818See More RSNA Education Exhibits How to Recognize Ductal Carcinoma in SITU: Tips for New ResidentsDigital Posters2020Catch Me Before I Go Invasive! The Role of Ultrasound in Depicting Calcified and Non-Calcified DCISDigital Posters2019Help Your Pathologist Help You: Successfully Arriving at a Diagnosis on Breast BiopsyDigital Posters2019 RSNA Case Collection Breast Papillomatosis with DCISRSNA Case Collection2020Ductal carcinoma in situRSNA Case Collection2020Invasive Papillary CarcinomaRSNA Case Collection2020 Vol. 257, No. 3 Metrics Altmetric Score PDF download

Infiltrating syringomatous adenoma presenting as microcalcification in the nipple on screening mammogram: case report and review of the literature of radiologic features

Infiltrating syringomatous adenoma (ISA) of the nipple, first described by Rosen in 1983 ( Am J Surg Pathol, 1983, 7, 739–745), is a rare benign tumor that can be misdiagnosed as a malignancy. ISA is characterized by its specific location in the subareolar region, its distinct histologic appearance resembling sweat duct or syringomatous tumors, and its locally infiltrating growth. We describes a case of ISA of the nipple presenting as microcalcification that was found on screening mammography. We also reviewed previously reported radiologic features of ISA.

A Bleeding Gastric Tumor With Concurrent Hypervascular Hepatic Nodules

Question: A 61-year-old man was admitted for dizziness and tarry stool for 5 days. Vital signs and laboratory results were within normal limits except for a decreased hemoglobin level of 6.6 g/dL (normal, 13.0–17.0). During an evaluation for suspected gastrointestinal bleeding using an endoscopic gastroduodenoscopy, a polypoid mass with central ulceration was detected in the antrum along the greater curvature of the stomach (FigureA). The results of contrast-enhanced computed tomography (CT; FigureB) revealed a 4-cm, well-circumscribed, homogeneously enhancing tumor (arrow) along the greater curvature side of the gastric antrum. Concurrently, multiple, small-sized, nodular lesions were suspected in the liver. Magnetic resonance imaging (MRI) of the liver was performed to obtain a differential diagnosis of the hepatic lesions. In the MRI (FigureC), multiple, small, nodular lesions (arrows) were seen in the liver, which showed a strong enhancement, similar to that of the gastric lesion depicted in the CT. The hepatic lesions were considered multiple metastases from the gastric tumor. What is the diagnosis for this patient? Look on pagepage 1798for the answer and see the Gastroenterologyweb site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Palliative wedge resection of the stomach and concurrent liver biopsy were performed. The surgical specimens from the stomach and liver showed identical histologic features of prominent vasculature and uniform tumor cells with nuclear atypia and high mitotic activity (FigureD). The results of immunohistochemical study revealed positive reactions to smooth muscle actin, vimentin, and synaptophysin. The pathologic diagnosis of malignant glomus tumor with hepatic metastases was made. Glomus tumors arise from modified smooth muscle cells of the glomus body, a specialized arteriovenous anastomosis that involves in thermoregulation. They are composed of epithelioid smooth muscle cells identical to those in the glomus body.1Tsuneyoshi M. Enjoji M. Glomus tumor: a clinicopathologic and electron microscopic study.Cancer. 1982; 50: 1601-1607Crossref PubMed Scopus (183) Google Scholar The majority of glomus tumors are benign, small, and solitary, and classically subungual in location. Glomus tumors of the stomach are rare and typically reported as well-circumscribed submucosal masses in the antrum. Most gastric glomus tumors are histologically and biologically benign.2Miettinen M. Paal E. Lasota J. et al.Gastrointestinal glomus tumors: a clinicopathologic, immunohistochemical, and molecular genetic study of 32 cases.Am J Surg Pathol. 2002; 26: 301-311Crossref PubMed Scopus (243) Google Scholar Most affected patients are asymptomatic or present with nonspecific symptoms, including epigastric discomfort or pain. However, larger lesions are prone to ulcerate and may cause gastrointestinal bleeding. On CT and MRI, these tumors show strong enhancement in the early phase of contrast material-enhanced images, reflecting their abundant vascularity, which persisted to the late phase.3Park S.H. Han J.K. Kim T.K. et al.Unusual gastric tumors: radiologic-pathologic correlation.RadioGraphics. 1999; 19: 1435-1446Crossref PubMed Scopus (83) Google Scholar The imaging findings of malignant glomus tumor of the stomach have not yet been reported. As shown in our case, malignant glomus tumor of the stomach demonstrated imaging findings similar to those of typically benign tumors. Although the majority of gastric glomus tumors can be considered benign, a small number of them may have a malignant behavior. An awareness of malignant potential of gastric glomus tumors correlated with their characteristic imaging can facilitate preoperative diagnosis.

A Rare Cause of Dysphagia: Malignant Pleural Mesothelioma in the Posterior Mediastinum

A 69-year-old man presented to the emergency room with dysphagia and vomiting. A computed tomographic scan revealed a posterior mediastinal mass surrounding the lower portion of the esophagus. Endoscopic examination demonstrated narrowing of the lower esophagus without malignant mucosal lesions. Thoracoscopic biopsies of the mediastinal mass failed to yield a pathologic diagnosis. The hyaluronic acid concentration in the left pleural effusion was remarkably high (755 mg/L), which is a finding strongly suggestive of malignant mesothelioma. Four months after the initial admission, a subcutaneous nodule was found in the left chest wall and a biopsy was taken. The histopathologic and immunohistochemical findings of the biopsy were consistent with the diagnosis of pleural malignant mesothelioma.

Imaging of acquired cystic disease-associated renal cell carcinoma by contrast-enhanced ultrasonography with perflubutane microbubbles and positron emission tomography-computed tomography

The preoperative assessment of renal cell carcinoma (RCC) complicated with acquired renal cystic disease in a 63-year-old male patient on long-term hemodialysis (30 years and 8 months) that was difficult because of no or poor contrast enhancement by dynamic CT scan is reported. Contrast-enhanced ultrasonography with perflubutane microbubbles and positron emission tomography-computed tomography (PET-CT) with 18F-fluorodeoxy glucose (FDG) in addition to dynamic CT were effective and useful for preoperative assessment of this patient. The pathological subtype of RCC in this patient was acquired cystic disease-associated RCC (ACD-associated RCC), which has been newly defined by Tickoo et al. (Am J Surg Pathol 30:141-153, 2006).

Levonorgestrel-releasing intrauterine system (LNG-IUS) as an effective treatment option for endometrial hyperplasia: a 15-year follow-up study

The levonorgestrel-releasing intrauterine system may represent an effective treatment option in >85% of endometrial hyperplasia cases, but histologic regression during and/or at the end of treatment does not assure stable recovery. We recommend periodic endometrial samplings for at least the first 2 years of follow-up and long-term clinical surveillance thereafter.

A 50-Year-Old Woman With a History of Atrial Fibrillation Presents With Acute Dyspnea and Pleuritic Chest Pain

A 50-Year-Old Woman With a History of Atrial Fibrillation Presents With Acute Dyspnea and Pleuritic Chest Pain

Hysteroscopic Diagnosis of Stromomyoma

Stromomyomas are relatively rare uterine tumors that exhibit ultrastructural characteristics of both endometrial stromal and smooth muscle cells [ 1 Tang C.-K. Toker C. Ances I.G. Stromomyoma of the uterus. Cancer. 1979; 43: 308-316 Crossref PubMed Scopus (51) Google Scholar , 2 Oliva E. Clement P.B. Young R.H. Scully R.E. Mixed endometrial stromal and smooth muscle tumors of the uterus: a clinicopathologic study of 15 cases. Am J Surg Pathol. 1998; 22: 997-1005 Crossref PubMed Scopus (136) Google Scholar , 3 Geetha V. Rupashree S. Bhat S.S. Endometrial stromal nodule with smooth muscle differentiation. Ind J Pathol Microbiol. 2008; 51: 76-77 Crossref PubMed Scopus (6) Google Scholar ]. In most cases, differentiation of endometrial stromal and smooth muscle tumors can be made solely by routine light microscopic examination. The World Health Organization currently recognizes the existence of such a hybrid neoplasm in its classification of uterine tumors [ 4 Scully R.E. Bonfiglio T.A. Kurman R.J. Silverberg S.G. Wilkinson E.J. Histological typing of female genital tract tumors. in: World Health Organization International Histological Classification of Tumors. 2nd ed. Springer-Verlag, Berlin1994: 22 Google Scholar ]. Imaging examinations often lead to the misdiagnosis of stromomyomas as either leiomyosarcomas or leiomyoma cystic degeneration, whereas reliance on histologic examinations often results in stromomyomas being misdiagnosed as cellular leiomyomas [ 5 Oliva E. Clement P.B. Young R.H. Mesenchymal tumors of the uterus: selected topics emphasizing diagnostic pitfalls. Curr Diagn Pathol. 2002; 8: 268-282 Abstract Full Text PDF Scopus (17) Google Scholar ].

Report From the Jerusalem Workshop on Lynch Syndrome-Hereditary Nonpolyposis Colorectal Cancer

A Workshop was held in Jerusalem, Israel, on October 26 and 27, 2009 to discuss the management of Lynch syndrome-hereditary nonpolyposis colorectal cancer (CRC), with the primary goal to develop consensus for the optimal management of this disease. A second goal was to identify areas of research with the potential to advance the clinical management of Lynch syndrome. The perspectives and recommendations from the workshop are meant to be a platform for discussion and deliberation. The Workshop was organized by Moshe Shike (Memorial Sloan Kettering Cancer Center, New York) and sponsored by The Colon Cancer Foundation. More details of each presentation are available in an on-line supplement.

Inflammatory Myofibroblastic Tumor of the Esophagus

Inflammatory myofibroblastic tumors are regarded as intermediate-grade tumors with a potential for recurrence. Although these lesions have been found in nearly every anatomic location, there are few documented cases of esophageal localization. The rare case reported here concerns a 55-year-old woman with an extremely large inflammatory myofibroblastic tumor of the esophagus; the tumor was 20 cm in length and 6 cm in diameter. Wide surgical excision was performed. Histopathologic and immunohistochemical analyses confirmed the diagnosis of an inflammatory myofibroblastic tumor. There was no recurrence or tumor metastasis 6 months after the operation.

A Primary Sclerosing Epithelioid Fibrosarcoma of the Pubic Bone, with Evidence of Divergent Epithelial Differentiation

Sclerosing epithelioid fibrosarcoma (SEF) is a rare variant of fibrosarcoma, described initially by Meis-Kindblom et al. in 1995 (Meis-Kindblom JM, Kindblom L-G, Enzinger FM. Sclerosing epithelioid fibrosarcoma: a variant of fibrosarcoma simulating carcinoma. Am J Surg Pathol. 1995;19:979–993): more than 80 cases have been documented clinicopathologically since. Bone is a rare primary site for SEF, with only 2 cases so far reported. This paper documents the detailed clinical, histological, immunohistochemical, and ultrastructural features of a case occurring in the pubic bone of a 57-year-old diabetic woman presenting with a history of pain and compromised mobility involving her hip. Radiology revealed a destructive lesion in the right pubic bone. The lesion was resected, and 7 months postoperatively it recurred. The patient died following metastases to multiple bony sites and liver, some 4 years after the onset of symptoms. Histologically, the tumor was consistent with SEF, although it showed some anomalous immunostaining, which, however, is typical of the tumor (for example, for S-100 protein and epithelial membrane antigen). By electron microscopy, some rough endoplasmic reticulum was present, but also tonofibrils and desmosomes. The overall features were of an SEF with the ultrastructural but incomplete immunohistochemical evidence for divergent epithelial differentiation. The differential diagnosis of this tumor is discussed.

Posttransplant Lymphoproliferative Disorder Following Kidney Transplant

Posttransplant Lymphoproliferative Disorder Following Kidney Transplant

Gastrointestinal Stromal Tumors—A Morphological and Immunohistochemical Study

The rationale of this study was to assess the morphological and immunohistochemical characteristics of gastrointestinal stromal tumor (GIST) along with their risk stratification. Record of 36 cases diagnosed as GIST over a period of 2 years (January 2007 to December 2008) was retrieved. Slides were reviewed for histological typing, immunohistochemical staining, and mitotic count. Cases were divided into very low, low, intermediate, and high-risk groups according to the Fletcher method of risk stratification (Table 1; Fletcher et al. (Int J Surg Pathol 10:81-89, 2002)). Mean, median, and mode were calculated for quantitative variables like age, tumor size, and mitotic count by using SPSS version 14. Frequencies and percentages were also calculated for qualitative variables like results of immunohistochemistry, tumor site, and histological subtypes. Out of 36 patients, 14 patients were male, and 22 were female. A total of 14 (39%) patients had tumor size between 2 and 5 cm, 13 (36%) patients had size between 5 and 10 cm, and 9 (25%) patients had size >10 cm. There was no tumor less than 2 cm in size. Twenty-one patients (58%) had mitoses <5/50 high power fields (HPF) while seven (20%) had mitoses between 5 and 10/50 HPF and eight (22%) >10/50 HPF. Thirty-one (86%) of cases were strongly positive for CD117 while CD34 was positive in 81% of the cases. Most frequent histological type was hypercellular spindle cell type, and most frequent site of presentation was stomach. Seven patients fell into low risk, ten patients intermediate risk, and 19 patients in high risk groups. There were no patients in very low risk group. By using microscopy and immunohistochemical techniques, GISTs can be diagnosed accurately and treated efficiently. Risk stratification and histological subtyping have emerged as efficient tools to predict malignant behavior.

Second toe swelling: Nora’s lesion or glomus tumour, case report and literature review

We report a rare case of bizarre parosteal osteochondromatous proliferation (BPOP, Nora's lesion) of the right second toe in a 60-year-old man who presented with painful, bluish and bulbous swelling of the right second toe without any break in the skin. Physical examination, plain radiography and magnetic resonance imaging (MRI) scan of the foot, histology of the excised tissue. Bizarre parosteal osteochondromatous proliferation. Radiographs showed a calcified/ossified lesion adjacent to the tuft of the terminal phalanx of the second toe. MRI showed a small low signal nodule on T1- and T2-weighted images in a subungual position adjacent to the terminal phalanx with sclerosis. The second toe was excised and the histology from excised tissue was consistent with "bizarre parosteal osteochondromatous proliferation". There was no malignant change on histology. Local excision of the entire lesion was done and there has been no recurrence to date. BPOP, although a benign lesion, behaves aggressively with rapid growth and has a high risk of local recurrence after local resection (Nora et al. in Am J Surg Pathol 7(3):245-250, 1983; Meneses et al. in Am J Surg Pathol 17(7):691-697, 1993). Its clinical presentation can be confused with glomus tumour, subungual exostosis and enchondroma. The distinguishing features of BPOP and several relevant different differential diagnoses are discussed in this case report.

Iron Ulcers

An 88-year-old woman with multiple medical problems including coronary artery disease and anemia who was on oral iron supplementation (ferrous sulfate tablets, 325 mg twice daily) was admitted to the hospital with fatigue and decreasing hematocrit levels. She had no history of peptic ulcer disease and denied using NSAIDs. An esophagogastroduodenoscopy showed several superficial ulcers and a deep ulcer in the stomach (Figure A). Biopsies of the ulcer showed erosive gastropathy with crystalline iron deposition consistent with oral iron supplementation–induced injury (Figures B and C). No Helicobacter pylori organisms were seen on the biopsy specimens.It is well-known that iron overdose can cause severe damage to the gastrointestinal tract, but there is less appreciation of the mucosal injury resulting from oral iron supplementation at therapeutic levels. Although the pathogenesis of mucosal injury caused by therapeutic iron medication is not well-understood, it is thought to be the result of a direct corrosive effect.1Haig A. Driman D.K. Iron-induced mucosal injury to the upper gastrointestinal tract.Histopathology. 2006; 48: 808-812Crossref PubMed Scopus (47) Google Scholar Ischemic mechanisms have also been hypothesized to play a role.Iron pill–associated gastrointestinal pathology is increasingly recognized by pathologists and gastroenterologists.1Haig A. Driman D.K. Iron-induced mucosal injury to the upper gastrointestinal tract.Histopathology. 2006; 48: 808-812Crossref PubMed Scopus (47) Google Scholar, 2Abraham S.C. Yardley J.H. Wu T. Erosive injury to the upper gastrointestinal tract in patients receiving iron medication.Am J Surg Pathol. 1999; 23: 1241-1247Crossref PubMed Scopus (104) Google Scholar, 3Eckstein R.P. Symons P. Iron tablets cause histopathologically distinctive lesions in mucosal biopsies of the stomach and esophagus.Pathology. 1996; 28: 142-145Crossref PubMed Scopus (47) Google Scholar, 4Kaye P. Abdulla K. Wood J. et al.Iron-induced mucosal pathology of the upper gastrointestinal tract: a common finding in patients on oral iron therapy.Histopathology. 2008; 53: 311-317Crossref PubMed Scopus (55) Google Scholar, 5Ji H. Yardley J.H. Iron medication-associated gastric mucosal injury.Arch Pathol Lab Med. 2004; 128: 821-822PubMed Google Scholar Iron tablets are widely used in the community, especially among older patients. It is therefore important to consider this entity in patients with gastric ulcers who are on oral iron supplementation and in whom the search for more common causes of gastric ulceration including NSAID use and H pylori infection has been negative. Iron pill–induced mucosal injury can be reversed by discontinuing the offending agent or switching to a less toxic form such as a liquid iron preparation. An 88-year-old woman with multiple medical problems including coronary artery disease and anemia who was on oral iron supplementation (ferrous sulfate tablets, 325 mg twice daily) was admitted to the hospital with fatigue and decreasing hematocrit levels. She had no history of peptic ulcer disease and denied using NSAIDs. An esophagogastroduodenoscopy showed several superficial ulcers and a deep ulcer in the stomach (Figure A). Biopsies of the ulcer showed erosive gastropathy with crystalline iron deposition consistent with oral iron supplementation–induced injury (Figures B and C). No Helicobacter pylori organisms were seen on the biopsy specimens. It is well-known that iron overdose can cause severe damage to the gastrointestinal tract, but there is less appreciation of the mucosal injury resulting from oral iron supplementation at therapeutic levels. Although the pathogenesis of mucosal injury caused by therapeutic iron medication is not well-understood, it is thought to be the result of a direct corrosive effect.1Haig A. Driman D.K. Iron-induced mucosal injury to the upper gastrointestinal tract.Histopathology. 2006; 48: 808-812Crossref PubMed Scopus (47) Google Scholar Ischemic mechanisms have also been hypothesized to play a role. Iron pill–associated gastrointestinal pathology is increasingly recognized by pathologists and gastroenterologists.1Haig A. Driman D.K. Iron-induced mucosal injury to the upper gastrointestinal tract.Histopathology. 2006; 48: 808-812Crossref PubMed Scopus (47) Google Scholar, 2Abraham S.C. Yardley J.H. Wu T. Erosive injury to the upper gastrointestinal tract in patients receiving iron medication.Am J Surg Pathol. 1999; 23: 1241-1247Crossref PubMed Scopus (104) Google Scholar, 3Eckstein R.P. Symons P. Iron tablets cause histopathologically distinctive lesions in mucosal biopsies of the stomach and esophagus.Pathology. 1996; 28: 142-145Crossref PubMed Scopus (47) Google Scholar, 4Kaye P. Abdulla K. Wood J. et al.Iron-induced mucosal pathology of the upper gastrointestinal tract: a common finding in patients on oral iron therapy.Histopathology. 2008; 53: 311-317Crossref PubMed Scopus (55) Google Scholar, 5Ji H. Yardley J.H. Iron medication-associated gastric mucosal injury.Arch Pathol Lab Med. 2004; 128: 821-822PubMed Google Scholar Iron tablets are widely used in the community, especially among older patients. It is therefore important to consider this entity in patients with gastric ulcers who are on oral iron supplementation and in whom the search for more common causes of gastric ulceration including NSAID use and H pylori infection has been negative. Iron pill–induced mucosal injury can be reversed by discontinuing the offending agent or switching to a less toxic form such as a liquid iron preparation.

Platelet-Derived Growth Factor Receptor Expression and Activation in Choroid Plexus Tumors

Choroid plexus tumors are intraventricular neoplasms predominantly affecting young children. In contrast to choroid plexus papillomas, choroid plexus carcinomas progress frequently, necessitating the development of adjuvant treatment concepts. Platelet derived growth factor (PDGF) signaling has been shown to support growth in a variety of tumors. The finding of PDGF receptor expression in choroid plexus tumors prompted us to elucidate PDGF receptor activation state using a novel method, in situ proximity ligation assay, on formalin-fixed, paraffin-embedded, archival samples of 19 choroid plexus tumors. As assessed by in situ proximity ligation assay, the proportion of phosphorylated PDGF receptor alpha was low in choroid plexus papillomas and choroid plexus carcinomas, whereas phosphorylated PDGF receptor beta was found to be significantly higher in choroid plexus carcinomas. In the immortalized choroid plexus epithelial cell line Z310 expressing PDGF receptor beta, PDGF-BB exhibited a time- and dose-dependent proliferative response, which was significantly attenuated by imatinib (gleevec). In conclusion, our findings suggest that PDGF receptor beta is functionally involved in the biology of choroid plexus tumors and may represent a molecular target for therapy. In addition, this study demonstrates the feasibility and usefulness of in situ proximity ligation assay for monitoring receptor tyrosine kinase activation in formalin-fixed, paraffin-embedded, archival tissues.

Vascular Endothelial Growth Factors C and D Induces Proliferation of Lymphangioleiomyomatosis Cells through Autocrine Crosstalk with Endothelium

Lymphangioleiomyomatosis (LAM) is a potentially fatal lung disease characterized by nodules of proliferative smooth muscle-like cells. The exact nature of these LAM cells and their proliferative stimuli are poorly characterized. Herein we report the novel findings that the lymphangiogenic vascular endothelial growth factors (VEGF) C and D induce LAM cell proliferation through activation of their cognate receptor VEGF-R3 and activation of the signaling intermediates Akt/mTOR/S6. Furthermore, we identify expression of the proteoglycan NG2, a marker of immature smooth muscle cells, as a characteristic of LAM cells both in vitro and in human lung tissue. VEGF-C-induced LAM cell proliferation was in part a result of autocrine stimulation that resulted from cross talk with lymphatic endothelial cells. Ultimately, these findings identify the lymphangiogenic VEGF proteins as pathogenic growth factors in LAM disease and at the same time provide a novel pharmacotherapeutic target for a lung disease that to date has no known effective treatment.

Mycophenolic Acid (Cellcept and Myofortic) Induced Injury of the Upper GI Tract

Mycophenolic acid (MPA) is an immunosuppressant drug commonly used in patients undergoing solid organ transplant. Although its pattern of inducing injury in the colon is well-known and features prominent crypt apoptosis that mimics graft-versus-host-disease, the injury pattern in the upper gastrointestinal (GI) tract is less extensively documented. We studied the pattern of upper GI tract injury in symptomatic patients taking MPA. Twenty solid organ transplant patients who were taking MPA and had concurrent upper GI tract biopsies were identified on a laboratory information system search. From these 20 patients, 17 duodenal, 18 gastric, and 7 esophageal biopsies were examined. All patients were symptomatic. Apoptosis and patterns of chronic and active injuries were assessed on standard hematoxylin and eosin, periodic acid-Schiff/Alcian blue, and Diff-Quik stained slides. To measure the significance of apoptosis, we standardized the apoptotic counts in normal biopsies using duodenal, gastric, and esophageal biopsies from 45 normal cases and performed statistical analysis. For the purposes of this study, we regarded apoptotic counts higher than the mean plus 2 SDs as significant. Thus the cut-off values for apoptosis were > or =2 apoptotic bodies/100 crypts for duodenum, > or =3/100 glands for stomach, and > or =2/10 high-power field for esophagus. GI-related symptoms and abnormalities manifested between 1 month and 10 years posttransplant and included diarrhea (55%); nausea (45%); abdominal pain (35%); vomiting (25%); GI bleeding (15%); dysphagia (10%); dyspepsia, anemia, and hematemesis (5% for each). Most (14 out of 17, 82%) duodenal biopsies showed apoptotic counts of > or =2/100 crypts, 28% (5 out of 18) of gastric biopsies showed apoptotic counts of > or =3/100 glands, and 57% (4 out of 7) of esophageal biopsies showed apoptotic counts of > or =2/10 high-power field. Four gastric biopsies showed a previously undescribed injury pattern of parietal cells resembling the ballooning degeneration. Additional pathologic findings included: chronic peptic duodenitis (6 out of 17, 35%), active duodenitis (1 out of 17, 6%), and celiac-like features (2 out of 17, 12%) in the duodenum; chemical gastropathy (3 out of 18, 17%), active chronic gastritis without Helicobacter pylori (2 out of 18, 11%), and erosion (1/18,6%) in the stomach; reactive epithelial change (3 out of 7, 43%), active esophagitis (3 out of 7, 43%), ulceration (2 out of 7, 29%), and erosion (1 out of 7, 14%) in the esophagus. Serum MPA levels were available in 7 patients, 6 of whom had abnormal duodenal apoptotic counts. On follow-up, available for 16 patients, symptoms improved in all the patients whose dose was decreased or whose medication was withdrawn (10 out of 10) and symptoms persisted in all the patients whose dose was not altered (6 out of 6). Follow-up biopsies after reduction of the medication dose were available for 1 patient and showed substantial reduction in apoptosis. In contrast, follow-up biopsies from 1 patient whose dosage was not altered showed persistent abnormal apoptotic counts in the duodenum. As noted by others (Parfitt JR, Jayakumar S, Driman DK. Am J Surg Pathol. 2008; 32:1367-1372), mycophenolate mofetil-associated injury of the upper GI tract, like that in the colon, is characterized by prominent apoptosis similar to that of mild or grade I graft-versus-host-disease injury. We offer apoptotic count guidelines, which we hope will facilitate recognition of mycophenolate mofetil-associated injury in the upper GI tract.

Papillary tumor of the pineal region

Tumors of the central nervous system (CNS) demonstrating papillary features, and particularly in the pineal region, are rare. Papillary tumor of the pineal region (PTPR) is a recently described rare neuroepithelial tumour included in the fourth edition of the World Health Organization (WHO) classification of tumours of the CNS, published in 2007. This new histopathological entity manifests in children and adults, with magnetic resonance (MR) imaging showing variable degree of T1 hyperintensity signal as well as contrast enhancement. In addition to the initial report of six cases by Jouvet et al. (Am J Surg Pathol 27:505–512, 2003) several case reports have been published in the literature to date. PTPR is characterized by presenting an epithelial-like cytology and a papillary architecture with immunoreactivity for broad-spectrum cytokeratins. Ultrastructurally observed features suggest ependymal differentiation and a possible origin from specialized ependymal cells of the subcommissural organ (SCO) has been postulated. The differential diagnosis of PTPR include pineal parenchymal tumors, choroid plexus tumors, papillary ependymoma, papillary meningioma, and metastasis. As a result of the rarity of these tumors, the biological behaviour of PTPR is not yet clear. It may correspond to WHO grades II or III. The high risk of local recurrence makes accurate surgery followed by radiotherapy necessary to achieve optimal treatment.