Reactive Epithelial Changes Research Articles

Systematic cytological evaluation and immunocytochemistry of minichromosome maintenance protein 2 and p53 significantly improve cytological diagnosis of pancreaticobiliary adenocarcinoma.

Endoscopic retrograde cholangiopancreatography (ERCP) brushing cytology often cannot distinguish adenocarcinoma from reactive epithelial changes. We attempted to improve the diagnostic sensitivity of ERCP using the following methods: systematic cytological evaluation, immunocytochemical examination of minichromosome maintenance proteins (MCM) 2 and p53, and a combination of these methods. ERCP specimens from 53 patients (13 benign and 40 malignant cases) were studied. First, we reclassified the cases into three categories according to the systematic cytological evaluation: negative, suspicious, and positive. Secondly, immunocytochemistry was performed for MCM 2 and p53. The cut-off values were set at 25% labeling index (LI) for MCM 2 and 10% LI for p53, respectively. We evaluated the sensitivity, specificity, and diagnostic accuracy. The sensitivity of the systematic cytological evaluation alone did not improve significantly, compared with the original screening examination (77% vs. 68%). The sensitivity of immunocytochemistry for MCM 2 and p53 was 90% (P < 0.05) and 68%, respectively. Applying only the suspicious or positive categories, the sensitivity improved significantly to 93% for the combination of systematic cytological evaluation and immunocytochemistry for MCM 2 and p53 (P < 0.01). In conclusion, the combination of morphology and immunocytochemistry for MCM 2 and p53 may help to overcome the diagnostic cytological difficulties of pancreaticobiliary adenocarcinoma.

CD133 as a Specific Marker to Differentiate In Situ and Invasive Carcinoma of Colon From Reactive Colonic Epithelial Changes

CD133 as a Specific Marker to Differentiate In Situ and Invasive Carcinoma of Colon From Reactive Colonic Epithelial Changes

A Rare Cause of a Cecal Polyp: An Unusual Presentation and Diagnosis

Purpose: An asymptomatic 45-year-old male was referred by PCP for cancer screening, as his mother had passed away from metastatic colon cancer. On colonoscopy, a sessile polyp was found in the cecum and a pedunculated polyp was found in the ascending colon, and biopsies were taken. Histology from the ascending colon showed a tubulovillous adenoma, but the cecal polyp showed spirochetosis and focal acute inflammation with reactive epithelial changes. Due to lack of clinical symptoms, metroniadazole therapy was deferred, and the patient has been doing well on follow-up. We report this case because intestinal spirochetosis (IS) presenting endoscopically as a cecal polyp is extremely rare and has not been reported before. Also, we are providing a brief review about intestinal spirochetosis for gastroenterologists as well as internists. Human IS was first reported in 1967, in a patient with chronic diarrhea, but the clinical significance of the condition is still poorly understood. It is unclear whether spirochetosis is an actual disease process or just colonization of the large bowel. Many cases of IS like ours can be asymptomatic and just an incidental discovery on colonoscopy, but in symptomatic cases, IS presents as chronic watery diarrhea and vague abdominal pain. In rare cases, it may be invasive and rapidly fatal. In the majority of the cases, colonic involvement in IS is endoscopically normal (1), which we believe makes our case unusual and interesting. There have been a few case reports in which IS has presented endoscopically as erythamatous lesions, diverticula, and ischemic ulcers. Treatment is still controversial for symptomatic patients.Figure: Colonic epithelium showing fuzzy blue line of spirochetes.Figure: Spirochetes attached to luminal border of epithelium.

Primary Retroperitoneal Mucinous Cystadenoma With a Sarcoma-like Mural Nodule

Primary retroperitoneal mucinous cystadenomas (PRMCs) are extremely rare tumors and their association with sarcoma-like mural nodules (SLMNs) has not been described thoroughly. The aim of this study is to characterize the gross and microscopic features and the immunohistochemical profile of the first case of PRMC with SLMN and to discuss the differential diagnosis of SLMNs. The literature related to primary retroperitoneal mucinous tumors is reviewed in an attempt to clarify the histogenesis of the epithelial and sarcomatoid components of the associated mural nodules. A 34-yr-old woman presented with a 14-cm retroperitoneal cystic lesion with a 6-cm mural nodule. An immunohistochemical study with a panel of 19 antibodies and a histochemical study for mucin stains were performed. The epithelial component of the PRMC showed positive staining for cytokeratin (CK) 7, CK AE1/3, epithelial membrane antigen, carcinoembryonic antigen, and calretinin. The neoplasm was not immunoreactive for CK 20, CK 5/6, and the other antibodies used in this study. In addition, it stained positively for mucin by mucicarmine, periodic acid-Schiff, and Alcian blue. The stromal cells of the cyst showed estrogen receptor positivity. SLMN cells were negative for all CKs and other epithelial markers used in the study, but they showed diffuse positive staining for vimentin and CD68, and positive staining for Ki-67 was demonstrated in 25% of these cells. The immunohistochemical and histochemical profiles of PRMC were similar to those of ovarian mucinous neoplasms and the mesothelium. The formation of SLMNs seems to be related to subepithelial hemorrhage and some reactive epithelial changes near the mural nodules. The specific immunohistochemical and morphologic features of SLMNs are helpful in differentiating them from malignant mural nodules, including true sarcomas, osteoclast-rich undifferentiated carcinomas, and carcinosarcomas. Such a differentiation is critical in view of its significant impact on the management of these neoplasms, particularly in young patients who desire to preserve their fertility.

S100P, von Hippel-Lindau gene product, and IMP3 serve as a useful immunohistochemical panel in the diagnosis of adenocarcinoma on endoscopic bile duct biopsy

Histopathologic distinction between benign and malignant bile duct epithelial lesions on endoscopic biopsies can be extremely challenging because of limited material, crush artifact, and compounding inflammatory and/or reactive changes particularly after stent placement. In this study, a total of 72 endoscopic bile duct biopsies, including 40 adenocarcinomas and 32 benign cases, were immunohistochemically examined for the expression of S100P, von Hippel-Lindau gene product (pVHL), and IMP3 to evaluate their diagnostic value. The results showed that 36 adenocarcinomas (90%) exhibited strong nuclear and cytoplasmic staining for S100P, of which 30 (83.3%) showed diffuse immunoreactivity. Intermediate to strong cytoplasmic staining for IMP3 was demonstrated in 31 tumors (77.5%) (15 diffuse, 16 focal). Completely negative staining for pVHL was observed in 37 adenocarcinomas. In the remaining 3 tumors, focal (1) or diffuse (2) membranous and cytoplasmic pVHL immunoreactivity was detected. Twenty-eight tumors (70%) showed a S100P+/IMP3+/pVHL- staining pattern, 6 (15%) with a S100P+/IMP3-/pVHL- pattern, and 2 (5%) with a S100P-/IMP3+/pVHL- pattern. All 32 benign biopsies were completely negative for IMP3 with the exception of 2 cases with focal dysplasia where focal immunoreactivity was observed. Thirty benign biopsies (93.8%) were positive for pVHL with a diffuse staining pattern observed in 28 cases (93.3%). Eight benign biopsies (25%) showed focal S100P positivity. Twenty-two benign biopsies (68.8%) displayed a S100P-/IMP3-/pVHL+ staining pattern. In conclusion, an immunohistochemical panel consisting of S100P, pVHL, and IMP3 can be helpful in distinguishing adenocarcinoma from reactive epithelial changes on challenging bile duct biopsies. The findings of focal S100P and/or IMP3 expression with reciprocal loss of pVHL immunoreactivity in a few benign biopsies suggest a use of these markers in the detection of early epithelial dysplasia that may be beyond histologic recognition.

Pseudoneoplastic Lesions of the Female Genital Tract

N Context.—Numerous benign, proliferative, or reactive processes, often related to hormone stimulation or inflammation, occur throughout the female genital tract and may mimic benign or malignant tumors. Several of the more common pseudoneoplastic lesions are discussed in this article, including microglandular hyperplasia of the cervix mimicking well-differentiated endometrial adenocarcinoma, reactive epithelial changes in the fallopian tubes mimicking adenocarcinoma or carcinoma in situ, and pregnancy changes in the ovary including pregnancy luteoma and large solitary luteinized follicular cyst of pregnancy and puerperium that may mimic ovarian neoplasms. Objectives.—To discuss and illustrate several common lesions of the female genital tract that mimic neoplasms. Data Sources.—Material derived from consultation cases and review of the literature. Conclusions.—Many benign hyperplastic or reactive processes that occur in the female genital tract may be mistaken for neoplasms both clinically and pathologically. Awareness of the features of such lesions will aid in their correct diagnosis and prevent overtreatment of benign processes. (Arch Pathol Lab Med. 2010;134:393–403) A variety of reactive and hyperplastic processes due to inflammation or repair and hormone or gonadotropin stimulation may mimic neoplasms throughout the female genital tract. Although many of these proliferative processes are difficult to distinguish from neoplasms, frequently their morphologic features allow their identification. Several such entities are discussed in this review, including microglandular hyperplasia of the cervix mimicking well-differentiated endometrial and endocervical adenocarcinoma, reactive epithelial changes in the fallopian tubes mimicking adenocarcinoma or carcinoma in situ, atypical and hyperplastic changes in endometriosis, and pregnancy changes in the ovary including pregnancy luteoma and large solitary luteinized follicular cyst of pregnancy and puerperium. Recognition of these pseudoneoplastic entities is of crucial importance in preventing overtreatment of such lesions that often occur in young women of reproductive age.

Protocol for the Examination of Specimens From Patients With Carcinoma of the Urethra

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations. The College regards the reporting elements in the ‘‘Surgical Pathology Cancer Case Summary (Checklist)’’ portion of the protocols as essential elements of the pathology report. However, the manner in which these elements are reported is at the discretion of each specific pathologist, taking into account clinician preferences, institutional policies, and individual practice. The College developed these protocols as an educational tool to assist pathologists in the useful reporting of relevant information. It did not issue the protocols for use in litigation, reimbursement, or other contexts. Nevertheless, the College recognizes that the protocols might be used by hospitals, attorneys, payers, and others. Indeed, effective January 1, 2004, the Commission on Cancer of the American College of Surgeons mandated the use of the checklist elements of the protocols as part of its Cancer Program Standards for Approved Cancer Programs. Therefore, it becomes even more important for pathologists to familiarize themselves with these documents. At the same time, the College cautions that use of the protocols other than for their intended educational purpose may involve additional considerations that are beyond the scope of these documents. PROTOCOL FOR THE EXAMINATION OF SPECIMENS FROM PATIENTS WITH CARCINOMA OF THE URETHRA

Pseudoneoplastic Lesions of the Female Genital Tract

Numerous benign, proliferative, or reactive processes, often related to hormone stimulation or inflammation, occur throughout the female genital tract and may mimic benign or malignant tumors. Several of the more common pseudoneoplastic lesions are discussed in this article, including microglandular hyperplasia of the cervix mimicking well-differentiated endometrial adenocarcinoma, reactive epithelial changes in the fallopian tubes mimicking adenocarcinoma or carcinoma in situ, and pregnancy changes in the ovary including pregnancy luteoma and large solitary luteinized follicular cyst of pregnancy and puerperium that may mimic ovarian neoplasms. To discuss and illustrate several common lesions of the female genital tract that mimic neoplasms. Material derived from consultation cases and review of the literature. Many benign hyperplastic or reactive processes that occur in the female genital tract may be mistaken for neoplasms both clinically and pathologically. Awareness of the features of such lesions will aid in their correct diagnosis and prevent overtreatment of benign processes.

Role of frozen section assessment for intraductal papillary and mucinous tumor of the pancreas

Intraductal papillary mucinous neoplasms (IPMN) of the pancreas include a spectrum of dysplasia ranging from minimal mucinous hyperplasia to invasive carcinoma and are extensive tumors that often spread along the ductal tree. Several studies have demonstrated that preoperative imaging is not accurate enough to adapt the extent of pancreatectomy and have suggested routinely using frozen sectioning (FS) to evaluate the completeness of resection and also to check if ductal dilatation is active or passive, in order to avoid an excessive pancreatic resection. Separate main duct and branch duct analysis is needed due to the difference in the natural history of the disease. FS accuracy averages 95%. Eroded epithelium on the main duct, severe ductal inflammation mimicking dysplasia and reactive epithelial changes secondary to obstruction can lead to inappropriate FS results. FS results change the planned extent of resection in up to 30% of cases. The optimal cut-off leading to extend pancreatectomy is not consensual and our standard option is to extend pancreatectomy if FS reveals: (1) at least IPMN adenoma on the main duct; or (2) at least borderline IPMN on branch ducts; or (3) invasive carcinoma. However, the decision to extend resection must be taken after a multidisciplinary discussion since it does not exclusively depend on the FS result but also on age, general condition and expected prognosis after resection. The main limitation of using FS is the existence of discontinuous ("skip") lesions which account for approximately 10% of IPMN in surgical series and can lead to reoperation in up to 8% of cases.

IMP3 expression in lesions of the biliary tract: a marker for high-grade dysplasia and an independent prognostic factor in bile duct carcinomas

The oncofetal protein IMP3 (insulin-like growth factor II mRNA binding protein 3) is expressed during embryogenesis and carcinogenesis. Various tumor types have been analyzed for IMP3 expression, which was exclusively found in tumor cells and correlated with increased tumor aggressiveness and reduced overall survival. To our knowledge, IMP3 expression has not been investigated in bile duct carcinomas. Using large tissue sections from resection specimens of the extrahepatic biliary tract, we analyzed IMP3 in normal bile ducts (n = 36), bile ducts with acute inflammation and reactive epithelial changes (n = 26), low-grade dysplasia (n = 9), and high-grade dysplasia (n = 11). Furthermore, IMP3 expression was assessed in bile duct carcinoma (n = 115) using clinically well-characterized tissue microarrays. The findings were correlated with clinical-pathologic parameters including survival. High-grade dysplasia was strongly positive for IMP3 in all cases studied compared with no or weak expression in normal, inflamed, and low-grade dysplastic bile ducts. Of the bile duct carcinomas 58.3% (67/115) were strongly positive for IMP3, which was associated with a higher proliferation rate (P = .004) and p53 positivity (P = .022). Patients with strong IMP3 expression had significantly reduced overall survival (P = .037) similarly to the subgroup of pT3 carcinomas (P = .007). In multivariate analysis, IMP3 expression was an independent prognostic factor for overall survival (P = .040, RR = 1.809). This comprehensive study shows that IMP3 is an independent prognostic biomarker in bile duct carcinoma. In addition, it may be a marker for high-grade dysplasia in the extrahepatic biliary tract.

Colonic sterilization for natural orifice translumenal endoscopic surgery (NOTES) procedures: a comparison of two decontamination protocols

This study aimed to evaluate the effect of two different sterilization protocols on the bacterial counts in the swine colon as preparation for natural orifice translumenal endoscopic surgery (NOTES) surgery. In this study, 16 swine were randomized to two different colonic sterilization protocols: low colonic irrigation using 300 ml of a 1:1 dilution of 10% povidone-iodine (Betadine) with sterile saline, followed by 1 g of cefoxitin dissolved in 300 ml of saline or two consecutive 300-ml irrigations using a quaternary ammonium antimicrobial agent (Onamer M). Colonic cultures were taken before colonic cleansing after a decontamination protocol and after completion of the NOTES procedure. The Invitrogen live/dead bacterial viability kit was used to assess for change in the bacterial load. A qualitative culture of peritoneal fluid was obtained at the end of the NOTES procedure. Colon mucosal biopsies obtained immediately after the sterilization procedure and at the 2-week necropsy point were evaluated for mucosal changes. Protocol 1 resulted in an average 93% decrease in live colonic bacteria versus 90% with protocol 2 (nonsignificant difference). After a NOTES procedure, group 1 had a 62% increase in live bacteria and group 2 had a 31% increase (nonsignificant difference). Peritoneal cultures also were obtained. Bacteria were isolated from the peritoneal fluid of all the animals, and two or more species were isolated from 75% of the animals. There was no evidence of peritoneal infection at necropsy. Reactive epithelial changes and mild inflammation were the only pathologic abnormalities. No changes were noted at histologic evaluation of colonic mucosa after 2 weeks, demonstrating that these were temporary changes. Colonic irrigation with Betadine and antibiotics are as effective for bacterial decontamination of the swine colon as a quaternary ammonium compound. The results of this study support the use of either protocol. Despite thorough decontamination, peritoneal contamination occurs. The significance of this for humans is unknown.

Biomarker (ProExTM C, p16INK4A, and MiB-1) distinction of high-grade squamous intraepithelial lesion from its mimics

Topoisomerase IIα and minichromosome maintenance protein 2 are proteins associated with aberrant S-phase induction. The current study evaluated the performance of these biomarkers (ProEx™ C; TriPath Oncology, Burlington, NC) compared with p16INK4A and MiB-1 in distinguishing high-grade squamous intraepithelial lesions (HSILs) from HSIL mimics. We collected archival cervical biopsy, cone, and curettage specimens from 96 cases in which the differential diagnosis of HSIL vs reactive epithelial changes was considered. Hematoxylin- and eosin-stained slides were reviewed independently by three pathologists and scored for the presence or absence of SIL. Immunostains for ProEx C, p16, and MiB-1 were available for 95, 96, and 59 samples, respectively, and classified blinded to histological interpretation. Strong nuclear and cytoplasmic staining for p16 and staining for MiB-1 and ProEx C that extended beyond the lower one-third of the epithelium were scored as positive. χ2-tests and receiver operating characteristic analysis were conducted to statistically compare biomarker immunostaining performance against majority histological interpretation of SIL. Agreement between pathologists was also assessed by the κ-statistic. Inter-observer agreement ranged from fair to moderate (κ=0.37–0.57). All three biomarkers correlated strongly with the majority diagnosis of SIL (P<0.001). Positive staining for ProEx C, p16, and MiB-1 was observed in 87% (N=52/60), 84% (N=51/61), and 94% (34/36), respectively, of SIL and negative in 71% (N=25/35), 63% (N=22/35), and 52% (N=12/23), respectively, of majority diagnoses of NoSIL. The combination of p16/ProEx C predicted more SIL (92%, N=33/36) and NoSIL (61%, N=14/23) than p16 plus MiB-1 (94%, N=34/36 and 43%, N=10/23), although this difference was not statistically significant. ProEx C appears to provide an equivalent level of sensitivity and a higher level of specificity for HSIL alone or in conjunction with p16. Its principal value may be in providing a lower false positive rate for NoSIL relative to MiB-1.

Helicobacter pylori Gastritis in Children Is Associated With a Regulatory T-Cell Response

Helicobacter pylori infection in children infrequently causes gastroduodenal mucosal ulceration. Because H pylori induces T-cell dependent gastric inflammation in adults and T regulatory (Treg) cells suppress T-cell-dependent pathology, we evaluated gastric histopathology and Treg cell responses in H pylori-infected children and adults. Gastric tissue from 36 children and 79 adults with abdominal symptoms in Santiago, Chile, was evaluated prospectively for H pylori bacteria and histopathology using the Sydney classification and Treg responses using immunoassay, immunohistochemistry, and real-time polymerase chain reaction. Eighteen (50%) of the children and 51 (65%) of the adults were infected with H pylori. Children and adults were colonized with similar levels of H pylori. However, the level of gastritis in the children was reduced substantially compared with that of the adults (P < .05). Coincident with reduced gastric inflammation, the number of Treg cells and levels of Treg cytokines (transforming growth factor [TGF]-beta1 and interleukin-10) were increased markedly in the gastric mucosa of H pylori-infected children compared with that of infected adults (P < .03 and < .05, respectively). Also, H pylori infection in the children was associated with markedly increased levels of gastric TGF-beta1 and interleukin-10 messenger RNA. Importantly, gastric TGF-beta1 in H pylori-infected children localized predominantly to mucosal CD25(+) and Foxp3(+) cells, indicating a Treg source for the TGF-beta1. Gastric pathology is reduced and local Treg cell responses are increased in H pylori-infected children compared with infected adults, suggesting that gastric Treg cell responses down-regulate the inflammation and ulceration induced by H pylori in children.

Inlet Patch Presenting With Food Impaction Caused by Peptic Stricture

A 73-year-old man presented to the emergency room complaining of difficulty swallowing beginning abruptly after eating a salmon fillet. Four years ago he presented to another hospital with similar symptoms and had a barium esophagogram that showed “narrowing of the esophagus.” Since then he has had 8–10 of these episodes, all of which resolved spontaneously. The patient’s additional medical history was unremarkable. He takes a daily aspirin. His physical examination, blood work, and lateral neck radiograph were normal. Urgent upper endoscopy was performed. At 22 cm from the incisors, boneless salmon was seen proximal to a luminal narrowing in the esophagus. After gently pushing the fish forward, a smooth 1-cm peptic stricture with surrounding edema and erythema was seen (FigureA). Immediately proximal and contiguous with the stricture was an area of velvety, dark pink mucosa (FigureB), which on histology was consistent with heterotopic gastric mucosa (FigureC). A biopsy examination of the strictured mucosa showed gastric and squamocolumnar junctional mucosa with reactive epithelial changes and chronic inflammation (FigureD). The stricture was dilated with Savory dilators (Cook Endoscopy, Winston-Salem, NC) and the patient was started on pantoprazole. One year later he remains asymptomatic. An inlet patch is an island of heterotopic gastric mucosa located in the proximal esophagus, usually within 3 cm of the upper esophageal sphincter. It can be recognized by its salmon-red, velvety mucosa with well-defined margins. The inlet patch was first described by Schmidt in 1805,1Schmidt FA. De mammalium oesophage at que ventriculo. Inaug Dissert, Halle, In: Bathenea, 1805.Google Scholar and can be found in up to 10% of adults undergoing upper endoscopy.2Von Rahden B. Stein H.J. Becker K. et al.Heterotopic gastric mucosa of the esophagus: literature-review and proposal of clinicopathologic classification.Am J Gastroenterol. 2004; 99: 543-551Crossref PubMed Scopus (134) Google Scholar Its cause most likely is congenital, and it rarely has any clinical significance. There are, however, case reports of complications of inlet patches, including ulceration, overt bleeding, esophageal perforation, tracheoesophageal fistula, and even adenocarcinoma.2Von Rahden B. Stein H.J. Becker K. et al.Heterotopic gastric mucosa of the esophagus: literature-review and proposal of clinicopathologic classification.Am J Gastroenterol. 2004; 99: 543-551Crossref PubMed Scopus (134) Google Scholar Multiple studies have shown that the parietal cells of an inlet patch can secrete a clinically significant amount of acid, and it is this acid that likely results in the complications described.3Galan A.R. Katza D.A. Castell D.O. Acid secretion from an esophageal inlet patch demonstrated by ambulatory pH monitoring.Gastroenterology. 1998; 115: 1574-1576Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, 4Hamilton J. Thune R. Symptomatic ectopic gastric epithelium of the cervical esophagus Demonstration of acid production with Congo red.Dig Dis Sci. 1986; 31: 337-342Crossref PubMed Scopus (58) Google Scholar By presenting this case, we hope to increase awareness that inlet patches sometimes can be clinically significant, and we remind the gastroenterologist of the importance of inspecting the proximal esophagus, which can be overlooked easily, when performing endoscopy for upper gastrointestinal symptoms.

Conjunctival T-cell Lymphoma: A Clinicopathologic Case Report

To report a patient with conjunctival T-cell lymphoma, an extremely rare entity.Single case report.Based on clinical examination, an excisional biopsy and immunostaining were performed on the conjunctival lesion. For management, we excised and performed triple freeze-thaw cryotherapy to the involved area, and we consulted the oncology service.T-cell and B-cell markers, and clinical examination of the lesion.Both examination and laboratory assessment revealed no evidence of systemic involvement. Conjunctival biopsy showed expansion of the substantia propria with an infiltrate of chronic inflammatory cells (including lymphocytes, plasma cells, and eosinophils), and prominent lymphocyte exocytosis with reactive epithelial changes. The CD-45 RO (T-cell marker) was strongly positive, whereas the CD-20 (B-cell marker) was negative. The T-cell receptor gene rearrangement was positive with beta clonality, confirming the diagnosis of T-cell lymphoma.T-cell lymphoma is a rare but possible diagnosis of gelatinous conjunctival lesions. The oncology consultants were reluctant to treat the patient with systemic chemotherapy or radiation because extraconjunctival extension could never be documented. The answer to the question of what is the most appropriate treatment for conjunctival T-cell lymphoma remains unknown.

Fundus Autofluorescence Before and After Photodynamic Therapy for Choroidal Neovascularization Secondary to Age-Related Macular Degeneration

To describe fundus autofluorescence patterns in choroidal neovascularization secondary to age-related macular degeneration before and after photodynamic therapy (PDT). Sixty-eight consecutive eyes were indicated for PDT after standard fluorescein angiography, which showed completely classic choroidal neovascularization (CNV) (n=52), occult with no classic CNV (n=7), and predominantly classic CNV (n=9). Standardized PDT was performed and patients were examined 2 to 3 months later. Angiography and autofluorescence measurements were performed again and compared with preoperative values. At baseline, autofluorescence was mainly decreased in areas of completely classic CNV (79%), but showed a regular or mottled pattern in occult CNV. A slightly increased (50%) or normal (50%) autofluorescence was seen at the rim of the classic lesions within the junctional zone. Membrane demarcation was improved (90%) in classic membranes 2 to 3 months after PDT. After PDT for occult membranes, a transformation into classic membranes with residual leakage and need for further PDT was observed (6 of 7 eyes), showing the described autofluorescence patterns. For the mixed type of CNV, both described patterns of autofluorescence distribution were found. Especially classic CNVs reveal distinct characteristics of significantly decreased autofluorescence, presumably due to their localization above the retinal pigment epithelium level, leading to blockage of autofluorescence. Autofluorescence patterns after PDT included enhanced demarcation of the membrane, suggesting reactive retinal pigment epithelial changes. Autofluorescence might be an interesting tool to distinguish noninvasively between classic and occult CNV in age-related macular degeneration and to monitor changes after PDT.

Pathology of the gallbladder: a concise review

While often underappreciated, the gallbladder may be affected by a variety of pathological processes that have specific clinical correlates. Reactive epithelial changes within typical cholecystitis may mimic dysplasia. Usual stone-associated cholecystitis has only mild inflammation, but variants of cholecystitis may have abundant xanthoma cells, eosinophils, or lymphocytes and plasma cells. Metaplasia from the normal columnar absorptive epithelium into mucinous epithelium occurs in a subset of cases, and a further subset may progress to dysplasia, which is thought to be the main precursor of invasive gallbladder carcinoma. Unlike the situation in the colon, adenomas in the gallbladder are rare and not likely to be the precursors of most carcinomas. Most invasive carcinomas of the gallbladder present at advanced stage, and therefore are highly lethal. While their morphology may be identical to that of other pancreatobiliary carcinomas, molecular data are emerging to suggest that these neoplasms are genetically distinct. Several more uncommon types of gallbladder carcinoma, such as papillary adenocarcinomas and small cell carcinoma, have different clinical implications, so it is important that they are recognized. p16 and p53 inactivation are consistent findings in gallbladder carcinomas, but novel abnormalities are revealed by recent global genetic analysis of these neoplasms.

Non-Endometrioid Carcinomas of the Uterine Corpus: A Review of Their Pathology With Emphasis on Recent Advances and Problematic Aspects

This review considers the clinical and pathologic features of the various histologic subtypes of endometrial carcinoma excluding those of pure endometrioid type, as the latter tumors were the subject of a previous contribution in the Journal (Vol. 9, No. 2). Non-endometrioid carcinomas, which account for about 10% of endometrial carcinomas, may pose a great array of problems in differential diagnosis, including their distinction not only from benign lesions but also endometrioid carcinoma and various tumors that may secondarily involve the uterine corpus. The most common subtypes are serous, mucinous, and undifferentiated. Rarer tumors are clear cell, squamous, transitional cell carcinomas, and a variety of poorly differentiated carcinomas with unusual forms of differentiation, such as hepatoid carcinoma, carcinomas with trophoblastic elements, and giant cell carcinoma. Mixed carcinomas, which are common, are also discussed, including those with a component of endometrioid carcinoma. The final section deals with endometrial involvement by metastatic tumors, lesions that, albeit rare, are sometimes neglected in the differential diagnosis of endometrial carcinomas. Important aspects emphasized are: (1) The potential for serous carcinoma to be mimicked by various forms of papillary endometrioid carcinoma. (2) The rarity of clear cell carcinoma and the greater frequency of clear cells in endometrioid carcinoma. (3) The frequency of mucinous epithelium in tumors of mixed cell type. (4) The frequency with which neoplastic mucinous epithelium originates from the endometrium. (5) The striking degree of differentiation of some squamous cell carcinomas. (6) The occasional predominance of non-endometrioid carcinomas (especially serous or undifferentiated carcinoma) within malignant mullerian mixed tumors. (7) The spectrum of reactive epithelial changes and other non-neoplastic abnormalities that may mimic serous or clear cell carcinoma.

Ki-67, cyclin E, and p16INK4 are complimentary surrogate biomarkers for human papilloma virus-related cervical neoplasia.

Prior studies of Ki-67, cyclin E, and p16 expression have suggested that these biomarkers may be preferentially expressed in cervical neoplasia. This study examined and compared the distribution of staining for these three antigens in 1) normal and reactive epithelial changes, 2) diagnostically challenging cases (atypical metaplasia and atypical atrophy), 3) squamous intraepithelial lesions (SIL), and 4) high-and low-risk human papilloma virus (HPV) type-specific SIL. One hundred four epithelial foci from 99 biopsies were studied, including low-grade squamous intraepithelial lesions (LSIL; 24), high-grade squamous intraepithelial lesions (HSIL; 36), mature or immature (metaplastic) squamous epithelium (29), and atrophic or metaplastic epithelium with atypia (15). Cases were scored positive for Ki-67 expression if expression extended above the basal one third of the epithelium, for cyclin E if moderate to strong staining was present, and for p16 if moderate to strong diffuse or focal staining was present. HPV status was scored by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of extracted DNA. Immunohistochemical findings were correlated with histologic and viral data. Overall, a histologic diagnosis of SIL correlated strongly with all of the biomarkers used (p <0.001). Positive scores for Ki-67, cyclin E, and p16 were seen in 68.4%, 96.7%, and 100% of LSILs and 94.7%, 91.6%, and 100% of HSILs, respectively. Positive predictive values of these three biomarkers for HPV were 82.4%, 89.5%, and 91.4%, respectively. The positive predictive value for HPV of either cyclin E or p16 was 88.7%. Strong diffuse staining for p16 was significantly associated with high-risk HPV-associated lesions. Normal or reactive epithelial changes scored positive for the three biomarkers in 7.7%, 8.0%, and 12%, respectively. Limitations in specificity included minimal or no suprabasal staining for Ki-67 in immature condylomas and occasional suprabasal staining of reactive epithelial changes (10%), diffuse weak nuclear cyclin E staining in some normal or metaplastic epithelia, and diffuse weak basal p16 staining and occasional stronger focal positivity in normal epithelia. Ki-67, cyclin E, and p16 are complementary surrogate biomarkers for HPV-related preinvasive squamous cervical disease. (Because cyclin E and p16 are most sensitive for LSIL and HSIL [including high-risk HPV], respectively, use of these biomarkers in combination for resolving diagnostic problems, with an appreciation of potential background staining, is recommended.)

Ischemic colitis with atypical reactive changes that mimic dysplasia (pseudodysplasia).

To describe reactive or reparative but atypical epithelial changes that occur in ischemic colitis. Surgical pathology files were searched for the diagnosis "ischemia, bowel." All cases were studied for reactive or reparative atypical changes. These were characterized and correlated with clinical information. Reactive atypical (pseudodysplastic) changes were found in 8 of 28 cases of ischemic bowel. The clinical history did not indicate ischemic colitis in 6 of 8 cases. In 3 cases, neutrophils in the lamina propria or acute cryptitis and crypt abscesses that suggested inflammatory bowel disease were noted. Ischemic changes in the bowel may produce reactive epithelial changes with sufficient atypia to simulate dysplasia. These may be associated with histologic changes that simulate inflammatory bowel disease, specifically ulcerative colitis. Since in most cases even the clinician is not sure whether the patient has ischemia or inflammatory bowel disease and because histologic changes of the latter may occur in ischemic bowel, there is a danger that the atypical reactive ischemic changes could be interpreted as true dysplasia that occurs in inflammatory bowel disease.