Jeremy R. Parfitt

Sessile serrated adenoma (SSA) vs. traditional serrated adenoma (TSA).

The morphologic distinction between various serrated polyps of the colorectum may be challenging. The distinction between sessile serrated adenoma (SSA) and traditional serrated adenoma (TSA) may be difficult using currently available criteria mostly based on cytologic characteristics. We have evaluated 66 serrated polyps including 29 SSA, 18 TSA, and 19 hyperplastic polyps for overall shape of the polyps, architectural features of individual crypts, the presence of eosinophilic cytoplasm, size and distribution of the proliferation and maturation zones, as well as Ki-67 and CK20 expression. The extent of the expression of CK20 and Ki-67 could not distinguish between the 3 types of serrated polyps, but the distribution of their expression was very helpful and differences were statistically significant. The distribution of Ki-67+ cells was the single most helpful distinguishing feature of the serrated polyp type (P<0.0001, χ2 test). Hyperplastic polyps had regular, symmetric, and increased Ki-67 expression. SSA had irregular, asymmetric, and highly variable expression of Ki-67. TSA had low Ki-67 expression, which was limited to “ectopic crypts” and admixed tubular adenomalike areas. In serrated polyps, ectopic crypt formation (ECF) defined by the presence of ectopic crypts with their bases not seated adjacent to the muscularis mucosae was nearly exclusive to TSA and was found in all cases, while the presence of cytologic atypia and eosinophilia of the cytoplasm were characteristic, but not limited to TSA. No evidence of ECF, but nevertheless abnormal distribution of proliferation zone was characteristic of SSA, whereas HP had neither. The presence of the ECF defines TSA in a more rigorous fashion than previous diagnostic criteria and also explains the biologic basis of exuberant protuberant growth associated with TSA and the lack of such growth in SSA. Recognition of this phenomenon may also help in exploring the genetic and molecular basis for differences between SSA and TSA, because these architectural abnormalities may well be a reflection of abnormalities in genetically programmed mucosal development.

Eosinophilic esophagitis in adults: distinguishing features from gastroesophageal reflux disease: a study of 41 patients

Eosinophilic esophagitis in adults is a recently described entity occurring in young males with dysphagia, in whom esophageal biopsies show eosinophilic infiltration. This study defines the clinical and histological features of patients with eosinophilic esophagitis, distinguishing it from gastroesophageal reflux disease. Esophageal biopsies from patients with dysphagia or esophagitis were reviewed blindly, and assessed for: epithelial eosinophil counts, presence of eosinophilic microabscesses, edema, basal zone hyperplasia, lamina propria papillae elongation, eosinophils and fibrosis. Clinical and endoscopic findings were obtained. Eosinophilic esophagitis was diagnosed with epithelial eosinophils ≥15 in ≥2 high-power fields (hpfs) or ≥25 in any hpf. Analysis was performed with Mann–Whitney, χ2 and ANOVA tests. Of 157 cases, 41 had eosinophilic esophagitis. Male gender (81%) and age ≤45 (54%) were commoner in patients with eosinophilic esophagitis (P=0.001, 0.010, respectively). Dysphagia was more common in eosinophilic esophagitis patients (63%, P<0.001); heartburn was more common in noneosinophilic esophagitis patients (53%, P<0.001). Endoscopic rings were more common in eosinophilic esophagitis patients (27%, P=0.023); hiatus hernia was more common in noneosinophilic esophagitis patients (11%, P=0.022). Eosinophils were more numerous in eosinophilic esophagitis biopsies (mean 39/hpf, P≤0.001). Only eosinophilic esophagitis biopsies had eosinophilic microabscesses (42%, P≤0.001). Edema, basal zone hyperplasia, lamina propria papillae elongation and lamina propria eosinophils were commoner in eosinophilic esophagitis (P=<0.001–0.002), while lamina propria fibrosis was specific for eosinophilic esophagitis (39%, P<0.001). Eosinophilic esophagitis is a disease with a predilection for young males with dysphagia and rings on endoscopy. Biopsies in eosinophilic esophagitis have high epithelial eosinophil counts, averaging nearly 40/hpf. Increased awareness of eosinophilic esophagitis is necessary, since treatment with allergen elimination or anti-inflammatory therapy may be more effective than acid suppression.

Mycophenolate Mofetil-related Gastrointestinal Mucosal Injury : Variable Injury Patterns, Including Graft-versus-Host Disease-like Changes

Mycophenolate mofetil (MMF) is a commonly used immunosuppressive drug used in the management of transplant recipients. Although gastrointestinal (GI) toxicity is a known complication of MMF, the literature characterizing the pathologic features of MMF in the GI tract is sparse. This study characterizes the pathologic features of MMF toxicity in both the upper and lower GI tract, correlating it with clinical and endoscopic findings. Seventy-five GI biopsies (9 esophageal, 15 gastric, 16 duodenal, 5 ileal, 30 colonic) from 46 transplant recipients from 2002 to 2006 were obtained and assessed for multiple histologic features. Clinical features were recorded for all cases and endoscopic findings. Only MMF patients showed ulcerative esophagitis (5/7 cases) and reactive gastropathy (4/10 cases). Only MMF patients showed graft-versus-host disease (GVHD)-like features in duodenal (4/12 cases) and ileal (1/5 cases) biopsies. GVHD-like changes were seen more frequently among patients on MMF compared with those not on MMF [9 (56%) vs. 2 (14%); P=0.017]. Crypt architectural disarray [12 (75%) vs. 2 (14%); P=0.001], lamina propria edema [9 (56%) vs. 2 (14%); P=0.017], increased lamina propria inflammation [13 (81%) vs. 3 (21%); P=0.001], dilated damaged crypts [7 (44%) vs. 1 (7%); P=0.024], and increased crypt epithelial apoptosis [9 (56%) vs. 2 (14%); P=0.017] were more common with MMF patients compared with non-MMF patients. In conclusion, pathologists should be aware of the potential manifestations of MMF toxicity throughout the GI tract, including ulcerative esophagitis, reactive gastropathy, and GVHD-like features in intestinal biopsies.

Recurrent hepatocellular carcinoma after transplantation: Use of a pathological score on explanted livers to predict recurrence

Milan and University of California at San Francisco (UCSF) criteria are used to select patients with hepatocellular carcinoma (HCC) for liver transplantation (LT). Recurrent HCC is a significant cause of death. There is no widely accepted pathological assessment strategy to predict recurrent HCC after transplantation. This study compares the pathology of patients meeting Milan and UCSF criteria and develops a pathological score and nomogram to assess the risk of recurrent HCC after transplantation. All explanted livers with HCC from our center over the 18‐yr period 1985 to 2003 were assessed for multiple pathological features and relevant clinical data were recorded; multivariate analysis was performed to determine features associated with recurrent HCC. Using pathological variables that independently predicted recurrent HCC, a pathological score and nomogram were developed to determine the probability of recurrent HCC. Of 75 cases analyzed, 50 (67%) met Milan criteria, 9 (12%) met only UCSF criteria and 16 (21%) met neither criteria based on explant pathology. There were 20 cases of recurrent HCC and the mean follow‐up was 8 yr. Recurrent HCC was more common (67 vs. 12%; P < 0.001) and survival was lower (15 vs. 83% at 5 yr; 15 vs. 55% at 8 yr; P < 0.001) with those who met only UCSF criteria, compared to those who met Milan criteria. Cryptogenic cirrhosis (25 vs. 5%; P = 0.015), preoperative AFP >1,000 ng/mL (20 vs. 0%; P < 0.001) and postoperative OKT3 use (40 vs. 15%; P = 0.017) were more common among patients with recurrent HCC. While microvascular invasion was the strongest pathological predictor of recurrent HCC, tumor size ≥3 cm (P = 0.004; odds ratio [OR] = 7.42), nuclear grade (P = 0.044; OR = 3.25), microsatellitosis (P = 0.020; OR = 4.82), and giant/bizarre cells (P = 0.028; OR = 4.78) also predicted recurrent HCC independently from vascular invasion. The score and nomogram stratified the risk of recurrent HCC into 3 tiers: low (<5%), intermediate (40–65%), and high (>95%). In conclusion, compared to patients meeting Milan criteria, patients who meet only UCSF criteria have a worse survival and an increased rate of recurrent HCC with long‐term follow‐up, as well as more frequent occurrence of adverse histopathological features, such as microvascular invasion. Application of a pathological score and nomogram could help identify patients at increased risk for tumor recurrence, who may benefit from increased surveillance or adjuvant therapy. Liver Transpl, 2007.

Malignant neoplasm of perivascular epithelioid cells of the liver.

Neoplasms of perivascular epithelioid cells (PEComas) have in common the coexpression of muscle and melanocytic immunohistochemical markers. Although this group includes entities with distinct clinical features, such as angiomyolipoma, clear cell sugar tumor of the lung, and lymphangioleiomyomatosis, similar tumors have been documented in an increasing diversity of locations. The term PEComa is now generally used in reference to these lesions that are not angiomyolipomas, clear cell sugar tumors, or lymphangioleiomyomatoses. While most reported PEComas have behaved in a benign fashion, malignant PEComas have occasionally been documented. We present a case of hepatic PEComa with benign histologic features, which nonetheless presented with metastases to multiple sites nearly 9 years later. This case represents the second documented malignant PEComa of the liver, as well as the longest follow-up of a surviving patient with a malignant PEComa, emphasizing both the need for criteria that more accurately predict the behavior of PEComas and the necessity of long-term follow-up of patients with PEComas.

The total mesorectal excision specimen for rectal cancer A review of its pathological assessment

Total mesorectal excision (TME) refers to the surgical removal of the complete perirectal soft tissue envelope, using sharp instruments under direct vision, and has become the contemporary standard of care for patients with rectal cancer. Pathologists play a key role in the evaluation of these specimens, including the quality assurance of surgical performance, as well as evaluation of the circumferential radial margin (CRM). While the latter is the most significant predictor of local recurrence, the quality of the excised mesorectum is another important factor in assessing the risk of local recurrence in patients with a negative CRM. Since proper pathological assessment of the TME specimen provides important prognostic information, as well as critical feedback to surgeons regarding technical performance, it is important to have adequate guidelines for the macroscopic handling of these specimens. The CLASSICC study of the Medical Research Council in the United Kingdom, as well as the Dutch TME trial have introduced a new standard for the pathological assessment of TME specimens, including an approach that involves assessment in both the fresh and fixed states, at least 48 hours of fixation of an intact specimen, with observations made on both the external appearance and cross-sectional slices. This article reviews the pathological assessment of the TME specimen, including basic definitions, current international guidelines, an approach to evaluating the mesorectum and a discussion of special issues relating to margins, lymph node retrieval and effects of neoadjuvant therapy.

Granular cell tumours of the gastrointestinal tract: expression of nestin and clinicopathological evaluation of 11 patients

Aims :u2002Granular cell tumours (GCTs) in the gastrointestinal (GI) tract are rare, with few series reported in the literature. Nestin is a recently identified intermediate filament protein that is expressed in neuroectodermal stem cells and skeletal muscle progenitor cells and has been shown to be expressed in gastrointestinal stromal tumours (GISTs) and GI schwannomas. Herein, we describe the clinicopathological and immunohistochemical features of 11 GI GCTs, introducing nestin as an additional marker that identifies these tumours.

Primary PEComa of the bladder treated with primary excision and adjuvant interferon-alpha immunotherapy: a case report.

BackgroundPerivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms of uncertain malignant potential, which have in common the co-expression of muscle and melanocytic immunohistochemical markers.Case presentationA 48-year-old man presented with dysuria, passage of urinary sediment and lower abdominal discomfort. A three centimeter mass was identified by cystoscopy in the posterior midline of the bladder. Computerized tomography suggested an enterovesical fistula. The patient underwent laparotomy, partial cystectomy and partial small bowel resection. Pathological examination revealed PEComa of the bladder. The patient underwent adjuvant interferon-α immunotherapy. Subsequent follow-up procedures, including cystoscopy and imaging, have not revealed evidence of recurrence. The patient is clinically free of disease 48 months after surgery.ConclusionThis case represents the second documented PEComa of bladder and demonstrates that adjuvant therapies, including anti-angiogenic and immunotherapy, may be considered for patients with locally advanced or metastatic genitourinary PEComa.

Venous Invasion in Colorectal Cancer Impact of an Elastin Stain on Detection and Interobserver Agreement Among Gastrointestinal and Nongastrointestinal Pathologists

Venous invasion (VI) is an independent prognostic indicator in colorectal cancer and may prompt consideration for adjuvant chemotherapy in patients with stage II tumors. Recent evidence suggests that VI is underreported in colorectal cancer and that detection may be enhanced by an elastin stain. This study aimed (1) to determine the impact of an elastin stain on VI detection and on interobserver agreement between gastrointestinal (GI) and non-GI pathologists, and (2) to identify factors associated with increased VI detection. Forty hematoxylin and eosin (H&E)-stained slides were circulated to 6 GI and 6 non-GI pathologists who independently assessed the VI status as positive, negative, or equivocal. Six weeks later, 40 corresponding Movat-stained slides were recirculated together with the original H&E slides and reassessed for VI status. Detection of VI was >2-fold higher with a Movat stain compared with an H&E stain alone (46.4% vs. 19.6%, P=0.001). GI pathologists detected VI more frequently than non-GI pathologists on both H&E (30.0% vs. 9.2%, P=0.029) and Movat (58.3% vs. 34.6%, P=0.018) stains. There was higher interobserver agreement in the case of a Movat stain, particularly for extramural VI (H&E: &kgr;=0.23 vs. Movat: &kgr;=0.41). A poststudy survey indicated that GI pathologists and non-GI pathologists applied similar diagnostic criteria but that GI pathologists more frequently applied “orphan arteriole” and “protruding tongue” signs as diagnostic clues to VI. This study confirms that VI is underdetected on H&E and highlights the role of elastin staining in improving VI detection and interobserver agreement. Strategies to improve VI detection are warranted.

In-situ and invasive carcinoma within a phyllodes tumor associated with lymph node metastases

BackgroundPhyllodes tumors (cystosarcoma phyllodes) are uncommon lesions in the female breast. Rarely, the occurrence of carcinoma within a phyllodes tumor has been reported in the literature, but has never been associated with lymph node metastases.Case presentationA 26-year-old woman presented with a firm, mobile, non-tender mass in the left breast and palpable lymph nodes in the left axilla. The excised lesion appeared well circumscribed and lobulated, with variable fleshy and firm areas. Microscopic examination showed a circumscribed fibroepithelial lesion with a well developed leaf-like architecture, in keeping with a benign phyllodes tumor. The epithelial component showed extensive high grade ductal carcinoma in-situ (DCIS) and invasive carcinoma of no special type, located entirely within the phyllodes tumor. Subsequent axillary lymph node dissection revealed metastatic carcinoma in four lymph nodes.ConclusionsAlthough rare, phyllodes tumors may harbor DCIS and invasive carcinoma, with potential for lymph node metastasis.