Background AKI is a complication of coronavirus disease 2019 (COVID-19) that is associated with high mortality. Despite documented kidney tropism of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are no consistent reports of viral detection in urine or correlation with AKI or COVID-19 severity. Here, we hypothesize that quantification of the viral load of SARS-CoV-2 in urine sediment from patients with COVID-19 correlates with occurrence of AKI and mortality. Methods The viral load of SARS-CoV-2 in urine sediments (U-viral load) was quantified by qRT-PCR in 52 patients with PCR-confirmed COVID-19 diagnosis, who were hospitalized between March 15 and June 8, 2020. Immunolabeling of SARS-CoV-2 proteins Spike and Nucleocapsid was performed in two COVID-19 kidney biopsy specimens and urine sediments. Viral infectivity assays were performed from 32 urine sediments. Results A total of 20 patients with COVID-19 (39%) had detectable SARS-CoV-2 U-viral load, of which 17 (85%) developed AKI with an average U-viral load four-times higher than patients with COVID-19 who did not have AKI. U-viral load was highest (7.7-fold) within 2 weeks after AKI diagnosis. A higher U-viral load correlated with mortality but not with albuminuria or AKI stage. SARS-CoV-2 proteins partially colocalized with the viral receptor ACE2 in kidney biopsy specimens in tubules and parietal cells, and in urine sediment cells. Infective SARS-CoV-2 was not detected in urine sediments. Conclusion Our results further support SARS-CoV-2 kidney tropism. A higher SARS-CoV-2 viral load in urine sediments from patients with COVID-19 correlated with increased incidence of AKI and mortality. Urinary viral detection could inform the medical care of patients with COVID-19 and kidney injury to improve prognosis.

Collapsing glomerulopathy is an aggressive form of focal segmental glomerulosclerosis with diverse causes. The presence of the apolipoprotein L1 (APOL1) high-risk genotype is a major risk factor for collapsing glomerulopathy in African Americans. Coronavirus disease 2019 (COVID-19) is an emerging pandemic with predominant respiratory manifestations. However, kidney involvement is being frequently noted and is associated with higher mortality. Currently, kidney pathology data for COVID-19 are scant and mostly come from postmortem findings. We report 2 African American patients who developed acute kidney injury and proteinuria in temporal association with COVID-19 infection. Kidney biopsy specimens showed collapsing glomerulopathy, endothelial tubuloreticular inclusions, and acute tubular injury, without evidence by electron microscopy or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in situ hybridization of viral infection of kidney cells. Both patients had the APOL1 high-risk genotype. We propose that collapsing glomerulopathy represents a novel manifestation of COVID-19 infection, especially in people of African descent with APOL1 risk alleles.

A 5-year-old boy presented with unilateral, focal superonasal conjunctival injection in the absence of vision changes or trauma. He was treated with a topical steroid for possible phlyctenule or episcleritis, but the lesion progressed to an elevated nodule, raising concern for nodular scleritis with no evidence of posterior involvement. Systemic work-up for underlying inflammatory conditions was unremarkable. There was some improvement in the level of injection with topical steroid, topical fluoroquinolone, and oral nonsteroidal anti-inflammatory drugs, but the nodular lesion persisted. Excisional biopsy revealed an inflamed dermoid cyst in the sub-Tenon's space.

Pleomorphic fibroma is a rare benign cutaneous neoplasm characterized by spindle‐shaped cells and multinucleated giant cells scattered throughout collagenous stroma. These morphologic features can lead to diagnostic confusion, including atypical lipomatous tumor as one consideration. In contrast to atypical lipomatous tumor, previous studies have found pleomorphic fibroma to be negative for MDM2 immunohistochemical staining and MDM2 gene amplification. Here, we present a case of pleomorphic fibroma of skin with nuclear MDM2 immunoreactivity in the absence of MDM2 gene amplification, underscoring the superiority of fluorescence in situ hybridization as a diagnostic test in this differential diagnosis. The RB1 locus is also explored for differential diagnosis with pleomorphic/spindle cell lipoma and related entities.

OBJECTIVE:To assess mature burn scars treated with a fractional carbon dioxide laser for changes in histological architecture, type I to III collagen ratios, density of elastic tissue, and subjective measures of clinical improvements.DESIGN:Uncontrolled, prospective study of patients with mature burn scars, from a clinical and histological perspective. Biopsy specimens were obtained before and 2 months after 3 treatment sessions. The tissue was prepared with Verhoff von Giesen (VVG) stain to discern elastic tissue and Herovici stain to differentiate types I and III collagen.SETTING:Subjects were recruited from the Grossman Burn Centers.PARTICIPANTS:Of 18 patients with mature burn scars, 10 completed the entire treatment protocol.INTERVENTION:Participants received 3 treatments with a fractional carbon dioxide laser.MAIN OUTCOME MEASURES:Vancouver Scar Scale and Patient and Observer Scar Assessment Scale survey scores. In histological analysis, imaging software was used to measure changes in collagen subtype and elastic tissue. A rating scale was developed to assess normal vs scar architecture.RESULTS:The first hypothesis that significant histological improvement would occur and the second hypothesis of a statistically significant increase in type III collagen expression or a decrease in type I collagen expression were confirmed. There were no significant changes in elastic tissue. Statistically significant improvements were seen in all survey data.CONCLUSIONS:Treatment with a fractional carbon dioxide laser improved the appearance of mature burn scars and resulted in a significant improvement in collagen architecture following treatment. Furthermore, in treated skin specimens, a collagen subtype (types I and III collagen) profile resembling that of nonwounded skin was found.

Iron deposition is seen in the mucosa of upper gastrointestinal tract, more frequently in the stomach, and may be observed in patients taking oral iron pills.Iron deposition is manifested by brown to black granules often arranged in linear manner on luminal surface, lamina propria, and cytoplasm of epithelial and reticuloendothelial cells.We encountered a unique pattern of iron deposits in an esophageal biopsy, in a brown linear manner along the intercellular space of squamous epithelium.The aim of this study is to further characterize the iron deposition in the esophageal mucosa.We retrospectively reviewed cases of esophageal biopsies within the period of September to November 2010.H&E-stained sections were reviewed by 2 pathologists.Esophageal biopsies with brown to black granular and linear deposits in the mucosa or those suspicious for iron (ie, coverslip artifact) are selected and stained with Gomori Prussian blue iron stain.Cases labeled esophageal biopsies without the representative squamous mucosal epithelium are excluded.We identified 220 consecutive esophageal biopsies.Histologic evaluations of H&E slides showed 3 biopsies containing brown to black granular or linear mucosal deposits and 7 with coverslip artifact represented by brown-black crystalline intercellular mucosal deposits all stained with Gomori Prussian blue iron stain.Only 1 esophageal biopsy (0.5%) was confirmed to contain iron deposit in a unique linear granular intercellular mucosal epithelium.It is essential to recognize that intercellular iron deposition in the esophageal mucosa is a unique pattern of iron deposition, although its association with intake of iron tablets, esophageal mucosal injury (erosion or ulceration), and reflux esophagitis is rare.

Autoimmune hepatitis (AIH)-primary biliary cirrhosis (PBC) overlap syndrome (OS) is a vaguely defined entity demonstrating features of AIH and PBC. We investigated the usefulness of IgG and IgM immunostaining for the distinction of AIH and PBC and their staining pattern in cases of possible OS. The approximate quantity of IgG+ and IgM+ periportal inflammatory cells in immunohistochemical analysis were compared in cases of AIH, PBC, and OS. AIH cases showed predominant IgG immunostaining of periportal inflammatory cells. A significant number of PBC cases also demonstrated IgG predominance rather than IgM. Six OS cases had IgG predominance, 4 had IgM predominance, and 1 was equivocal. The usefulness of IgG and IgM immunostaining is limited in PBC cases with IgM predominance for excluding AIH. IgG predominance is not specific for AIH. OS does not demonstrate either IgG or IgM predominance (P > .2) and does not help classify OS into either category.

A 58-year-old woman with a surgical history of jejunoileal bypass in 1980 for weight reduction sought medical attention with multiple complaints. The patient had not been taking any nutritional supplements since her bypass surgery, 26 years previously. She was found to have osteomalacia, chronic diarrhea, secondary hyperparathyroidism, and hyperoxaluria with a frequent history of nephrolithiasis. Because of her severe osteodystrophy and metabolic complications, reversal of her jejunoileal bypass was recommended. Reversal of the jejunoileal bypass with a sleeve gastrectomy was performed. Laparotomy revealed brown discoloration of the entire alimentary limb with atrophy of the bypassed intestinal limb. Histologic examination of the resected small bowel demonstrated brown pigment deposits within smooth muscle cells of the bowel wall. The pigment stained positive with Fontana-Masson most likely representing lipofuscin. We report a case of brown bowel syndrome complicating jejunoileal bypass, the first case reported in the literature to the best of our knowledge.

Glomeruloid hemangiomas (GHs) are glomeruli-like capillary tufts lined by endothelial cells that contain periodic acid-Schiff (PAS) positive eosinophilic globules (EGs). These hemangiomas are characteristic cutaneous manifestation of POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, and Skin changes). Hemangiomas histologically identical to GHs but not associated with POEMS have recently been designated as papillary hemangiomas. In this report, we present solitary head and neck GHs in 3 patients, 2 without POEMS, with particular attention to the characteristic EGs. We performed immunostains for hemoglobin A, kappa and lambda light chains, factor VIII-related antigen, CD31 and CD34, PAS stain after diastase digestion (PASD), and electron microscopic examinations on routinely fixed tissues containing EGs. Eosinophilic globules stained uniformly positive for PASD but only peripherally positive for hemoglobin and light chains on surfaces, with interiors negative for antigens. Factor VIII-related antigen and CD31 and CD34 confirmed cells containing EGs to be endothelial. Electron microscopic examination suggested that EGs are enlarged secondary lysosomes (thanatosomes). These features fail to support red blood cells or immunoglobulins as EG constituents. Glomeruloid hemangiomas may be vascular proliferations stimulated by endothelial cells' protein phagocytosis but not by phagocytosis of either hemoglobin-containing red blood cells or immunoglobulins. The vascular lesions in POEMS syndrome appear identical to papillary hemangioma in cases without the other syndromic manifestations.

2721 Introduction: In majority of hematologic malignancies, morphology supplemented with immunohistochemistry (IHC) and/or flow cytometric (FCM) immunophenotyping can discriminate between a malignant and reactive lymphoproliferation. In about 10% of cases, additional ancillary studies such as T cell receptor (TCR) gamma gene rearrangement and immunoglobulin heavy chain (IgH) gene rearrangement are ordered to provide additional evidence that “suspicious” histological changes may represent a malignant process. T cell lymphomas in particular are often difficult to distinguish from atypical T cell proliferations. Our study focuses on the contribution of TCR gamma clonality assessment assay towards accurate diagnosis and staging of hematologic malignancies. Methods: From January to October 2006, 111 specimens were evaluated for TCR gamma clonality in the AP Molecular Pathology laboratory at Henry Ford Hospital. Histologic evaluation, IHC, and sometimes FCM evaluations were also performed on all cases. Specimen types were as follows: skin biopsy (74), lymph node biopsy (15), peripheral blood (7), bone marrow (5), and miscellaneous extranodal lymphoid proliferations (10). DNA was isolated and subjected to PCR amplification for TCR gene rearrangement (TCR Gamma Gene Rearrangement Assay, In Vivo Scribe, San Diego, CA). The amplified PCR products were analyzed by capillary electrophoresis. Gene rearrangement test results were correlated with other histologic and clinical features. Results: Of the111 specimens, 50 demonstrated clonal TCR gamma gene rearrangement (31 skin, 8 lymph node, 5 blood, 4 bone marrow, and 2 breast biopsy specimens). For 15 of these, all other histological, IHC and FCM (when available) findings were inconclusive. Positive gene rearrangement results prompted closer monitoring of these patients, and T cell malignancies were subsequently confirmed in most of these cases. TCR gamma gene rearrangement testing was negative in 52 cases of atypical lymphoid proliferation, confirming other histologic findings. Nine of the specimens (7 skin and 2 lymph node) gave what appeared to be false negative results. Four of these subsequently demonstrated T cell clonality when repeat biopsies were tested. Conclusion: As with many diseases with a spectrum of clinical and pathologic findings, demonstration of clonal T cell proliferation can confirm diagnosis, or help to raise suspicion of a T cell lymphoma. In cases of atypical lymphoid proliferation, negative results are highly suggestive of a reactive process. The results of this study demonstrate that, in addition to histologic diagnosis, ancillary gene rearrangement studies can further define difficult cases, especially difficult to diagnose dermatologic malignancies.

There is more scientific and clinical evidence over the past several years that an increased melanoma risk exists from indoor UVA (320–400 nm) exposure from tanning sessions either at home or in salons. Indoor UVA bulbs also emit approximately 5 to 10% UVB (280–320 nm) too. Both UVA and UVB have been implicated in the pathogenesis of melanoma.Case Report: A 22 y/o red-haired, brown eyed female with Type II skin developed a left upper arm nodular melanoma after six years of 20 minute daily tanning salon sessions. She also sunbathed in Michigan seasonal sunlight on clear sunny days for up to 60 minutes per day too. The nodular melanoma was 1.95-mm tumor thickness and Clark’s level III. The mitotic rate was high. There was no ulceration of the tumor. The regional lymph nodes were not involved nor was there evidence of distant metastasis. All of the immunostains for melanoma were positive. Re-excision with a 2-cm margin was performed on the original excision site.Comment: Federal guidelines recommend no more than 150 tanning sessions per year. This patient had approximately 2100 sessions (350/year × 6) over a period of six years. In addition, the FDA guidelines recommend only 4 minimal erythemal doses (MEDs) per single-session or a maximum of 12 MEDs per week of UVA radiation. Our patient had a total of 2016 MEDs over a six-year period or more than 2.4 times the maximum recommendation of the FDA. Thus, stricter Federal/FDA guidelines are needed regarding “daily tanning sessions” and in regards to maximum total dose/MEDs that the public may be exposed to either at home or in tanning salons.1Ultraviolet A and melanoma a review.J Am Acad Dermatol. 2003; 48 (Mar): 464-465Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar, 2Risk of cutaneous malignant melanoma in relation to use of sunbeds further evidence for UVA carcinogenicity.Br J Cancer. 2000; 82 (May): 1593-1599Crossref PubMed Google Scholar, 3The Photobiology of UVA Can It Lead to Melanoma?. P551 AAD Poster Session, 61st Annual Meeting, San Francisco, CA2003: 21-26Google Scholar, 4Increased Melanoma Risk from Indoor UVA Tanning. The Skin Cancer Foundation. www.skincancer.org/melanoma.tanning.phpGoogle Scholar There is more scientific and clinical evidence over the past several years that an increased melanoma risk exists from indoor UVA (320–400 nm) exposure from tanning sessions either at home or in salons. Indoor UVA bulbs also emit approximately 5 to 10% UVB (280–320 nm) too. Both UVA and UVB have been implicated in the pathogenesis of melanoma. Case Report: A 22 y/o red-haired, brown eyed female with Type II skin developed a left upper arm nodular melanoma after six years of 20 minute daily tanning salon sessions. She also sunbathed in Michigan seasonal sunlight on clear sunny days for up to 60 minutes per day too. The nodular melanoma was 1.95-mm tumor thickness and Clark’s level III. The mitotic rate was high. There was no ulceration of the tumor. The regional lymph nodes were not involved nor was there evidence of distant metastasis. All of the immunostains for melanoma were positive. Re-excision with a 2-cm margin was performed on the original excision site. Comment: Federal guidelines recommend no more than 150 tanning sessions per year. This patient had approximately 2100 sessions (350/year × 6) over a period of six years. In addition, the FDA guidelines recommend only 4 minimal erythemal doses (MEDs) per single-session or a maximum of 12 MEDs per week of UVA radiation. Our patient had a total of 2016 MEDs over a six-year period or more than 2.4 times the maximum recommendation of the FDA. Thus, stricter Federal/FDA guidelines are needed regarding “daily tanning sessions” and in regards to maximum total dose/MEDs that the public may be exposed to either at home or in tanning salons.1Ultraviolet A and melanoma a review.J Am Acad Dermatol. 2003; 48 (Mar): 464-465Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar, 2Risk of cutaneous malignant melanoma in relation to use of sunbeds further evidence for UVA carcinogenicity.Br J Cancer. 2000; 82 (May): 1593-1599Crossref PubMed Google Scholar, 3The Photobiology of UVA Can It Lead to Melanoma?. P551 AAD Poster Session, 61st Annual Meeting, San Francisco, CA2003: 21-26Google Scholar, 4Increased Melanoma Risk from Indoor UVA Tanning. The Skin Cancer Foundation. www.skincancer.org/melanoma.tanning.phpGoogle Scholar

PURPOSE: Stapling of the ileal pouch-anal anastomosis with preservation of the anal transitional zone remains controversial because of concerns about the potential risk of dysplasia and cancer. The natural history and optimal treatment of anal transitional zone dysplasia ten or more years after surgery are unknown. This study establishes the risk of dysplasia in the anal transitional zone and the outcome of a conservative management policy for anal transitional zone dysplasia, with a minimum of ten years’ follow-up after ileal pouch-anal anastomosis. METHODS: A total of 289 patients undergoing anal transitional zone–sparing stapled ileal pouch-anal anastomosis for inflammatory bowel disease between 1986 and 1990 were studied. Patients undergoing anal transitional zone–sparing ileal pouch-anal anastomosis who were studied with serial anal transitional zone biopsies for at least ten years postoperatively were included (n = 178). Median follow-up was 130 (range, 120–157) months. RESULTS: Anal transitional zone dysplasia developed in 8 patients 4 to 123 (median, 9) months after surgery. There was no association with gender, age, preoperative disease duration, or extent of colitis, but the risk of anal transitional zone dysplasia was significantly associated with cancer or dysplasia as a preoperative diagnosis or in the proctocolectomy specimen. Dysplasia was high grade in two patients and low grade in six. Two patients with low-grade dysplasia on two or more occasions after detection of low-grade dysplasia underwent completion mucosectomy and perineal pouch advancement with neo–ileal pouch-anal anastomosis. One patient with high-grade dysplasia on two occasions was to undergo completion mucosectomy, but this was not technically feasible. Partial mucosectomy with vigorous anal transitional zone biopsy was performed with close postoperative surveillance. Biopsies were negative for dysplasia. The second recently diagnosed patient with high-grade dysplasia underwent examination under anesthesia with negative anal transitional zone biopsies and will be kept under close surveillance. No cancer in the anal transitional zone was found during the study period. The 4 other patients with low-grade dysplasia on 1 or 2 occasions were treated expectantly and have been dysplasia free for a median of 119 (range, 103–133) months. CONCLUSIONS: Anal transitional zone dysplasia after stapled ileal pouch-anal anastomosis is infrequent and is usually self-limiting. Anal transitional zone preservation did not lead to the development of cancer in the anal transitional zone with a minimum of ten years of follow-up. Long-term surveillance is recommended to monitor dysplasia. If repeat biopsy confirms persistent dysplasia, mucosectomy with perineal pouch advancement and neo–ileal pouch-anal anastomosis is recommended.

PURPOSE:Pouchitis is the most common complication of ileal pouch-anal anastomosis for ulcerative colitis. Our previous study suggested that symptoms alone are not reliable for the diagnosis of pouchitis. The most commonly used diagnostic instrument is the 18-point pouchitis disease activity index consisting of three principal component scores: symptom, endoscopy, and histology. Despite its popularity, the pouchitis disease activity index has mainly been a research tool because of costs of endoscopy (especially with histology), complexity in calculation, and time delay in determining histology scores. It is not known whether pouch endoscopy without biopsy can reliably diagnose pouchitis in symptomatic patients. The aim of the present study was to determine whether omitting histologic evaluation from the pouchitis disease activity index significantly affects the sensitivity and specificity of diagnostic criteria for pouchitis.METHODS:Ulcerative colitis patients with an ileal pouch-anal anastomosis and symptoms suggestive of pouchitis were evaluated. Patients with chronic refractory pouchitis and Crohn's disease were excluded. Patients with pouchitis disease activity index scores of seven or more were diagnosed as having pouchitis. Different diagnostic criteria were compared on the basis of the pouchitis disease activity index component scores. Nonparametric receiver-operating-characteristic curves were used to measure proposed pouchitis scores' diagnostic accuracy compared with diagnosis from the pouchitis disease activity index. The receiver-operating-characteristic area under the curve measured how much these diagnostic strategies differed from each other.RESULTS:Fifty-eight consecutive symptomatic patients were enrolled; 32 (55 percent) patients were diagnosed with pouchitis. With the use of the pouchitis disease activity index as a criterion standard, the use of only symptom and endoscopy scores (modified pouchitis disease activity index) produced an area under the curve of 0.995. Establishing a cut-point of five or more for diseased patients resulted in a sensitivity equal to 97 percent and specificity equal to 100 percent.CONCLUSIONS:Diagnosis based on the modified pouchitis disease activity index offers similar sensitivity and specificity when compared with the pouchitis disease activity index for patients with acute or acute relapsing pouchitis. Omission of endoscopic biopsy and histology from the standard pouchitis disease activity index would simplify pouchitis diagnostic criteria, reduce the cost of diagnosis, and avoid delay associated with determining histology score, while providing equivalent sensitivity and specificity.

PURPOSE: Pouchitis is the most common complication of ileal pouch-anal anastomosis for ulcerative colitis. Our previous study suggested that symptoms alone are not reliable for the diagnosis of pouchitis. The most commonly used diagnostic instrument is the 18-point pouchitis disease activity index consisting of three principal component scores: symptom, endoscopy, and histology. Despite its popularity, the pouchitis disease activity index has mainly been a research tool because of costs of endoscopy (especially with histology), complexity in calculation, and time delay in determining histology scores. It is not known whether pouch endoscopy without biopsy can reliably diagnose pouchitis in symptomatic patients. The aim of the present study was to determine whether omitting histologic evaluation from the pouchitis disease activity index significantly affects the sensitivity and specificity of diagnostic criteria for pouchitis. METHODS: Ulcerative colitis patients with an ileal pouch-anal anastomosis and symptoms suggestive of pouchitis were evaluated. Patients with chronic refractory pouchitis and Crohn's disease were excluded. Patients with pouchitis disease activity index scores of seven or more were diagnosed as having pouchitis. Different diagnostic criteria were compared on the basis of the pouchitis disease activity index component scores. Nonparametric receiver-operating-characteristic curves were used to measure proposed pouchitis scores' diagnostic accuracy compared with diagnosis from the pouchitis disease activity index. The receiver-operating-characteristic area under the curve measured how much these diagnostic strategies differed from each other. RESULTS: Fifty-eight consecutive symptomatic patients were enrolled; 32 (55 percent) patients were diagnosed with pouchitis. With the use of the pouchitis disease activity index as a criterion standard, the use of only symptom and endoscopy scores (modified pouchitis disease activity index) produced an area under the curve of 0.995. Establishing a cut-point of five or more for diseased patients resulted in a sensitivity equal to 97 percent and specificity equal to 100 percent. CONCLUSIONS: Diagnosis based on the modified pouchitis disease activity index offers similar sensitivity and specificity when compared with the pouchitis disease activity index for patients with acute or acute relapsing pouchitis. Omission of endoscopic biopsy and histology from the standard pouchitis disease activity index would simplify pouchitis diagnostic criteria, reduce the cost of diagnosis, and avoid delay associated with determining histology score, while providing equivalent sensitivity and specificity.

Figure 1. Erythematous plaques on the trunk and upper extremities. Similiar lesions appeared on the patient's face and lower extremities. A 56-year-old white man had a 4-year history of a solitary, well-circumscribed, erythematous plaque on the left scapular area. One year before presentation, he developed hypoesthesia and paresthesia in the right ring finger and both feet. Subsequently , 5 months prior to presentation, the patient received amoxicillin as treatment for bronchitis. A few days after the initiation of treatment, he noticed multiple lesions on his face, trunk, and extremities (figure 1) that were similar to the one on his scapula. The skin in these plaques had decreased sen

OBJECTIVES: Pancreatic endocrine tumors (PETs) have variable prognoses, and predictors of survival are lacking. PETs can be difficult to distinguish histologically from aggressive pancreatic neoplasms such as acinar cell carcinoma. Telomerase is a ribonuclear protein that maintains the length of the telomere and induces cell immortality. Telomerase is present in 95% of pancreatic adenocarcinoma and is associated with aggressive tumor behavior. Our aim is to determine telomerase activity in PETs and investigate its potential role as a prognostic indicator. METHODS: Telomerase detection using the telomeric repeat amplification protocol was performed on frozen surgical archived pancreatic endocrine tissue from 30 patients with PETs identified by light microscopy (hematoxylin-eosin stain). All results were confirmed with internal controls. A patient’s survival was measured from the time of surgery. Acinar cell differentiation (presence of zymogen granules) was determined by electron microscopy. Follow-up data were acquired via telephone interview, medical record review, and death certificates. RESULTS: Three of 30 PETs diagnosed by light microscopy were telomerase positive: three were considered nonfunctional, and two of these three patients had extrapancreatic disease. All three telomerase-positive cases were reclassified as either acinar cell carcinoma (two cases) or mixed acinar-endocrine cell carcinoma (one case). All three patients (mean age = 63 yr) died from tumor progression within 2 yr of surgery (mean = 1.6 yr ± 0.5 SD). The remaining PETs were telomerase negative: 13 insulinomas, four nonfunctional, two sporadic glucagonomas, one gastrinoma, one vipoma, one carcinoidlike PET, and five PETs from three patients with multiple endocrine neoplasm syndrome type 1 and two patients with von Hippel-Lindau syndrome. Excluding insulinomas, 12 of 14 patients with telomerase-negative PETs had extrapancreatic disease. Nevertheless, Kaplan-Meier survival estimates for these 12 patients were significantly longer than for patients with telomerase-positive acinar cell carcinoma (92% vs 0% at 2 yr, p = 0.001, log rank test). The survival of all telomerase-negative PETs (n = 27) was significantly longer than that of the patients with telomerase-positive acinar cell carcinoma (93% vs 0% at 2 yr, p = 0.0001). CONCLUSIONS: Telomerase activity helps to identify acinar cell carcinomas that histologically resemble PETs, which accounts for the poor prognosis demonstrated in these patients. The absence of telomerase activity in most PETs may be responsible for their indolent clinical course. Telomerase may identify potentially progressive tumors, such as acinar cell carcinoma, and may be useful in selecting patients for more aggressive treatment.