Epidermal growth factor receptor positivity in angiomyolipoma contiguous to renal cell carcinoma: report of two cases with immunohistochemical analysis.

Renal cell carcinoma (RCC) and angiomyolipoma (AML), usually unassociated, have occasionally been reported to coexist in the same person, usually in patients with tuberous sclerosis. We report two patients without tuberous sclerosis whose nephrectomy specimens contained renal cell carcinoma directly contiguous to AML in the same kidney. When immunohistochemical staining for epidermal growth factor receptor (EGFR) was performed on the RCCs, an interesting observation was made. The contiguous AMLs demonstrated strong positivity for EGFR, a feature not observed in isolated AMLs. The significance of this finding is unclear. Paracrine regulation may exist between these two closely adjacent tumors leading to synchronous high expression of EGFR in the AML adjacent to RCC, which may in turn affect the biologic behavior of these AMLs, compared to AMLs not associated with RCC.

Colonic perforation resulting from ingested chicken bone revealing previously undiagnosed colonic adenocarcinoma: report of a case and review of literature.

An 86 year old male with a four-day history of nonspecific gastrointestinal symptoms was found on colonoscopy to have evidence of sigmoid colon obstruction and possible perforation. Emergent operative exploration revealed diffuse peritonitis, sigmoid perforation, adjacent dense adhesions, and a foreign body protruding through the perforated area. Pathologic examination showed the foreign body to be a sliver of bone consistent with chicken bone and the sigmoid subacute perforation to be associated distally with a circumferential ulcerated obstructing mass, microscopically seen to be transmurally infiltrating adenocarcinoma, signet-ring cell type. There was extensive acute and organizing peritonitis, 100% Escherichia coli was cultured from peritoneal fluid, and the patient died two days postoperatively with sepsis and hypotension. This appears to be the fifth reported case of colonic perforation resulting from foreign body perforation due to previously undiagnosed adenocarcinoma. The four previously reported cases were all deeply invasive adenocarcinoma of sigmoid colon, and the foreign bodies included three chicken/poultry bones and a metallic staple. These five cases are highly unusual examples of a potentially lethal malignant neoplasm being clinically revealed by a usually (but not always) innocuous event, the ingestion of a small foreign body.

Correlation of epidermal growth factor receptor with morphological features of colorectal advanced adenomas: a pilot correlative case series.

INTRODUCTION: The epidermal growth factor receptor (EGFR) pathway is important to colorectal carcinogenesis. Although EGFR is described to be overexpressed in adenomas, to the authors' knowledge, its relationship with advanced features in adenomas and as a marker for adenoma progression has not been studied. METHODS: Initially, 13 polyps (sizes 3 mm-5.5 cm) from a 63-year-old patient were stained for EGFR. Subsequently, a validation group of 95 adenomas from 16 patients were graded semiquantitatively for EGFR staining. Size and villous features of the adenomas were evaluated by 2 independent pathologists and compared with EGFR expression. To be classified as advanced, adenomas needed to be greater than 1 cm and fulfill 1 of the 2 criteria-villous component >20% to 25% or presence of high-grade dysplasia. RESULTS: In the index case, the large 5.5 cm tubulovillous adenoma had EGFR positivity in all of its neoplastic cells, whereas another 2 cm tubular adenoma with focal villous features had 30% EGFR positivity. All other polyps and normal colonic mucosa were negative for EGFR. In 95 adenomas from 16 additional patients, there was a significant correlation of EGFR positivity with adenoma size ≥1 cm and villous features (all P < 0.001). The odds of EGFR expression in advanced adenomas were 17.3 times higher than nonadvanced adenomas (P < 0.001). CONCLUSIONS: These findings suggest that EGFR overexpression is associated with advanced colorectal adenomas. Further larger studies are needed to explore EGFR expression as a biomarker for adenoma progression.

Greater interobserver agreement by endoscopic mucosal resection than biopsy samples in Barrett's dysplasia.

BACKGROUND & AIMS: Endoscopic mucosal resection (EMR) is an important diagnostic, staging, and therapeutic tool for patients with Barrett's esophagus (BE)-associated neoplasia. We analyzed the histopathologic characteristics of specimens collected during EMR compared with biopsy specimens from patients with BE and assessed interobserver variability in pathologists' assessment of EMR and biopsy specimens. METHODS: We evaluated EMR (n = 251) and biopsy (n = 269) specimens collected from patients with BE at 2 tertiary referral centers. A detailed histologic analysis was performed for each EMR and biopsy specimen to determine the grade of dysplasia, depth of the specimen, proportion of specimen with dysplasia, and quality of samples. Interobserver agreement for both biopsy and EMR specimens (among 4 experienced pathologists) was calculated by using kappa statistics. RESULTS: Histologic analysis showed that submucosa was present in the majority of EMRs, compared with biopsy specimens (88% vs 1%, P < .0001). Almost all biopsy specimens (99%) included lamina propria. However, the muscularis mucosa was observed in only 58% of biopsy specimens. For both EMR and biopsy specimens, the highest grade of dysplasia comprised < or =25% of the total area in >50% of the specimens. Interobserver agreement on the diagnosis of dysplasia was significantly greater for EMR specimens than biopsy specimens (low-grade dysplasia, 0.33 vs 0.22, P < .001; high-grade dysplasia, 0.43 vs 0.35, P = .018). CONCLUSIONS: Submucosa can be examined in most samples collected from EMR; the distribution of neoplasia is focal within biopsy and EMR specimens. There is more interobserver agreement among pathologists in the analysis of EMR samples than biopsy specimens for the diagnosis of dysplasia.

Amelanotic malignant melanoma: two collision tumors presenting as basal cell carcinoma and atypical fibroxanthoma.

Collision (contiguous) tumors of the skin can result in misleading clinicopathological presentations, and the choice of appropriate diagnostic techniques may prevent incomplete diagnosis and management. We report 2 cases of collision tumors involving amelanotic malignant melanoma of the back. One patient is a 79-yr-old male with an 8.7 x 5.5 x 4.5 cm polypoid lesion that on shave biopsy was diagnosed as basal cell carcinoma. Subsequent excision showed that the lesion was largely composed of amelanotic melanoma underlying a relatively small and thin basal cell carcinoma, and this probably would have been demonstrated in a punch (rather than shave) biopsy. The other patient is a 71-yr-old male with a 1 cm exophytic lesion on the back, which was determined microscopically to be melanoma, and a 0.6 cm papule on the back. This lesion was composed of 2 distinct contiguous neoplastic infiltrates, the predominant component being an atypical fibroxanthoma and the smaller component an amelanotic melanoma (primary vs metastatic), with diagnostic confirmation requiring multiple immunohistochemical stains.

Narrow-band imaging colonoscopy--a pilot feasibility study for the detection of polyps and correlation of surface patterns with polyp histologic diagnosis.

BACKGROUND: Colonoscopy is the preferred screening method for colorectal cancer. However, it has a substantial miss rate for colon polyps, and several techniques have been attempted to improve this limitation. Narrow-band imaging (NBI) is a novel technology that enhances the visualization of surface mucosal and vascular patterns. OBJECTIVE: The aim of this study was to determine the detection rate of additional polyps by NBI after removal of polyps visualized by standard white light colonoscopy (WLC) and to correlate the surface mucosal and vascular patterns with polyp histologic diagnosis. DESIGN: This was a prospective pilot feasibility study. SETTING: Kansas City Veterans Affairs Medical Center. PATIENTS: Subjects referred for screening colonoscopy were prospectively enrolled. METHODS: Subjects underwent colonoscopy after enrollment. After intubation of the cecum, colonic segments were sequentially examined, initially with WLC with removal of polyps followed by re-examination of the same segment with NBI. Additional polyps seen with NBI were photographed for their surface patterns and then removed. The total number of polyps visualized by WLC and NBI was calculated and the surface patterns were then correlated with polyp histologic features. RESULTS: Forty patients were enrolled in the study, all men, 32 white. The mean age was 62 years. A total of 72 polyps were detected by WLC (43 tubular adenoma, 28 hyperplastic polyps), whereas NBI detected an additional 51 polyps, of which 29 were tubular adenomas and 22 were hyperplastic. Five different surface/vascular patterns were observed: fine capillary network with absent mucosal pattern, circular pattern with dots, round/oval pattern, tubular pattern, and gyrus pattern. The sensitivity, specificity, and overall accuracy of the first two patterns for hyperplastic polyps were 86%, 96%, and 92%, respectively, and of the latter three patterns for tubular adenomas were 96%, 86%, and 92%, respectively. CONCLUSIONS: This pilot study demonstrates the feasibility of polyp detection and histologic correlation with NBI. These findings need to be confirmed in future randomized controlled trials.

Pseudoepitheliomatous hyperplasia - an unusual reaction following tattoo: report of a case and review of the literature.

A 59-year-old woman presented with an itchy and uncomfortable raised lesion at a tattoo site (Fig. 1) on the lateral aspect of the left leg, just above the ankle. The tattoo had been placed 2 years before her presentation and the tattoo site was sun exposed. Immediately after she had the tattoo, she noticed redness of the skin. After a week, a pruritic and red scaly nodule developed that continued to gradually enlarge until her presentation. The patient had tried topical vitamin A and D ointment with no relief. The patient also had tattoos on the arms without any noticeable skin changes. The patient reported that the tattoo procedure on her leg was more painful than that on her arms, and was performed by a different (and perhaps inexperienced) tattoo artist. The original tattoo contained red, green, and yellow pigments. A diagnosis of tattoo granuloma was considered; squamous cell carcinoma and fungal infection were included in the differential diagnosis. A punch biopsy was performed, followed by complete surgical excision of the lesion with a split-thickness skin graft from the right thigh. The skin excision specimen showed a 3 x 2.5-cm granular and pitted pink lesion with well-demarcated, somewhat irregular borders. The lesion was raised 0.5 cm above the skin surface. The lesion was present in the center of the original tattoo. Portions of the original tattoo with green and blue-green pigmentation were visible on either side of the lesion. No satellite lesions were identified. Microscopically, the raised lesion demonstrated striking pseudoepitheliomatous hyperplasia, with irregular acanthosis of the epidermis and follicular infundibula, hyperkeratosis, and parakeratosis (Fig. 2). Follicular plugging was present with keratin-filled cystic spaces. There was a brisk mononuclear inflammatory infiltrate in the dermis, composed primarily of lymphocytes, with admixed plasma cells and histiocytes. Giant cells were occasionally identified. Dermal pigment deposition was noted both within the lesion and in the surrounding skin, corresponding to the original tattoo. Variable dermal fibrosis was noted, with thick collagen bundles in some areas. There was no evidence of epidermal keratinocytic atypia, dyskeratosis, or increased suprabasal mitotic activity. Special stains (periodic acid-Schiff and acid-fast) for microorganisms were negative.

Dysgenetic hypoplastic kidney simulating metastatic lung carcinoma.

We describe a 57-year-old male with prior history of an absent right kidney and kidney transplant who was found to have lung cancer. Integrated positron emission tomography (PET) and computerized tomography (CT) scan was done for staging and showed uptake in the right upper lung primary and right renal fossae region which was suggestive of metastatic disease. An excisional biopsy of the right renal fossae mass showed that it was a hypoplastic kidney simulating a metastatic focus on PET scan. The patient eventually underwent a left upper lobectomy with a final pathological stage of T2N0M0. Positive PET scan areas should be biopsied to confirm the presence of metastatic disease before excluding patients from surgical treatment.

Detection of cardia intestinal metaplasia: do the biopsy number and location matter?

BACKGROUND AND AIM: Presence of intestinal metaplasia in the gastric cardia (cardia intestinal metaplasia, CIM) has been reported in 5-34% of patients undergoing upper endoscopy and is a topic of interest given the rising incidence of cancer in this location. The aim of this article is to determine the prevalence of CIM in biopsies obtained from two separate locations within the gastric cardia. METHODS: Patients presenting to the endoscopy unit for upper endoscopy for any symptoms were invited to participate in the study. The biopsy protocol included: eight biopsies from the gastric cardia, four from upper cardia (forceps across the squamocolumnar junction), four from lower cardia (within 1 cm of upper cardia), and four each from the gastric body and antrum. All cardia biopsies were stained with hematoxylin and eosin (H&E) and alcian blue at pH 2.5 for the presence of goblet cells and the body/antrum biopsies were stained with Steiner silver stain for Helicobacter pylori detection. In patients testing negative for H. pylori by histology, a serology test was performed. RESULTS: Sixty-five patients have been evaluated by this protocol; median age 54 yr (range: 34-81 yr), 63 males, 53 Caucasians, and 12 African Americans. The detection of CIM was as follows: upper cardia only, 7, both upper and lower cardia, 5, and lower cardia only, 7. Thus, CIM was detected in 12 patients (18%) in the upper cardia biopsies, in 12 patients (18%) in the lower cardia; overall prevalence of CIM was 29% (19 patients). Fifty-eight percent of CIM patients tested positive for H. pylori by either histology or serology. The addition of serology allowed for the detection of eight additional H. pylori-positive CIM patients. CONCLUSIONS: The prevalence of CIM in this study was similar (18%, four biopsies) at each location; however, if both locations were considered (eight biopsies), the prevalence increased to 29%. Thus, CIM prevalence may vary depending on the number of biopsies obtained as well as on the location of biopsies. Use of additional testing detects more patients who are H. pylori positive and should be performed if association of CIM with H. pylori is contemplated. Future endoscopic studies of the gastric cardia should specify the location of biopsies, the number of biopsies obtained, and the tests used to diagnose H. pylori.

Hepatocellular carcinoma diagnosed by fine-needle aspiration of the parotid gland.

Hepatocellular carcinoma rarely metastasizes to the salivary glands. We report a case of a 47-yr-old man who presented with a right parotid lesion that was diagnosed by fine-needle aspiration (FNA) biopsy as a metastatic lesion suggestive of hepatocellular carcinoma with similar findings in a subsequent intraoral incisional biopsy. The patient's serum alpha-fetoprotein level was within normal limits at the time of diagnosis. CT scan revealed a mass in the liver, but a liver biopsy was not performed. The patient deteriorated rapidly and died about 4 mo later. An autopsy confirmed the presence of hepatocellular carcinoma with distant metastases to unusual sites, including the parotid gland, orbit, and calvarium, bypassing more common sites such as the lungs. This is the second known reported case in which hepatocellular carcinoma presented as a salivary gland metastasis. In both cases the diagnosis was made by FNA biopsy, illustrating the utility of this method for diagnosing uncommon metastatic salivary gland lesions.

Metastatic renal cell carcinoma of spleen diagnosed by fine-needle aspiration.

Splenic metastases are infrequent, and determination of the primary site by fine-needle aspiration (FNA) can be complex. We report the case of a 65-year-old man who was found to have a large heterogeneously enhancing 8 x 7-inch splenic mass by abdominal computed tomography (CT). FNA by transesophageal endoscopic ultrasonography demonstrated atypical cells conclusive for malignancy and consistent with metastatic renal cell carcinoma based on cytomorphology, histochemical lipid positivity, and immunohistochemical positivity for cytokeratin, vimentin, and renal cell carcinoma marker. Repeat CT with and without arteriovenous contrast demonstrated bilateral renal cysts, including a 0.9 x 0.8-cm lesion on the left with significant enhancement. Splenectomy confirmed the radiological and cytological findings, and left kidney exploration and nephrectomy demonstrated a small (1.5 cm) lower pole renal cell carcinoma of chromophil (papillary) type, histologically similar to the splenic metastasis. This case demonstrates the diagnostic importance of interdisciplinary involvement (oncology, radiology, gastroenterology, pathology, and general and urologic surgery); cytomorphology; histochemistry, including fat stain on frozen cell block; and immunohistochemistry, including the recently developed renal cell carcinoma marker.

Telomerase reverse transcriptase subunit immunoreactivity: a marker for high-grade prostate carcinoma.

BACKGROUND: Telomerase, a ribonucleoprotein complex that maintains telomeric DNA, has been detected in 67-93% of prostate carcinomas by telomeric repeat-amplification protocol assay (involving polymerase chain reaction). One study used in situ hybridization in nine patients; however, to date, no immunohistochemical results have been published. METHODS: From two hospitals, the authors compiled data on 62 patients who underwent prostatectomy from January 1996 to May 2001. Representative tissue sections were immunostained with a polyclonal antibody to telomerase reverse transcriptase (TERT), the catalytic subunit of telomerase. Staining was evaluated by two observers and was correlated with grade, stage, and biochemical failure. There were 28 sections from low-grade to intermediate-grade tumors (Gleason score, 3-6), 14 sections with a Gleason score of 3 + 4 = 7, 9 sections with a Gleason score of 4 + 3 = 7, and 11 sections from high-grade tumors (Gleason score, 8-10). RESULTS: From low-grade to high-grade tumors, the four groups described above disclosed nuclear reactivity in 64%, 100%, 100%, and 100% of sections, respectively. Mean percentages of 5%, 15%, 40%, and 51% of nuclei were reactive in the respective groups (P < 0.0001) with intratumoral heterogeneity. The percent of reactive tumor nuclei was not correlated with pathologic stage (P = 0.32) or margin status (P = 0.35). The basal cell layer in sections of high-grade prostatic intraepithelial neoplasia (HGPIN) and benign/atrophic acini was reactive; secretory cells were reactive in 13 of 34 HGPIN foci (38%) in 1-20% of nuclei and were never reactive in benign acini. Lymphocytes and skeletal muscle were reactive. Weak, nonspecific, cytoplasmic staining was noted in benign and tumor acini. CONCLUSIONS: Like cytokeratin 34betaE12, nuclear anti-TERT reactivity is a basal cell marker in nonneoplastic prostatic acini. Anti-TERT reactivity is acquired by secretory cells in tumorigenesis, but consistent reactivity is restricted to high-grade carcinoma (Gleason primary pattern >or=4). This histologic evidence suggests that higher grade tumors have maximally activated telomerase and may be most responsive to antitelomerase therapy.