Arch Pathol Lab Med Research Articles

Does Routine Repeat Testing of Critical Values Offer Any Advantage Over Single Testing

N Context.—Before being communicated to the caregiver, critical laboratory values are verified by repeat testing to ensure their accuracy and to avoid reporting false or erroneous results. Objective.—To determine whether 2 testing runs offered any advantage over a single testing run in ensuring accuracy or in avoiding the reporting of false or erroneous results. Design.—Within the hematology laboratory, 5 tests were selected: hemoglobin level, white blood cell count, platelet count, prothrombin time, and activated partial thromboplastin time. A minimum of 500 consecutive critical laboratory test values were collected retrospectively for each test category. The absolute value and the percentage of change between the 2 testing runs for each critical value were calculated and averaged for each test category and then compared with our laboratory’s preset, acceptable tolerance limits for reruns. Results.—The mean results obtained for the absolute value and the percentage of change between the testing runs were 0.08 g/dL (1.4%) for hemoglobin levels, 50 cells/mL (10.2%) for white blood cell counts, 1500 cells/mL (9.9%) for platelet counts, 0.7 seconds (1.4%) for prothrombin time, and 5.1 seconds (4.4%) for activated partial thromboplastin time (all within our laboratory’s acceptable tolerance limits for reruns). The percentage of specimens with an absolute value or a mean percentage of change outside our laboratory’s acceptable tolerance limits for reruns ranged between 0% and 2.2% among the test categories. No false or erroneous results were identified between the 2 testing runs in any category. Conclusions.—Routine, repeat testing of critical hemoglobin level, platelet count, white blood cell count, prothrombin time, and activated partial thromboplastin time results did not offer any advantage over a single run. (Arch Pathol Lab Med. 2011;135:440–444)

Hyalinizing spindle cell tumor with giant rosettes

Low-grade fibromyxoid sarcomas are uncommon deep-seated soft tissue neoplasms that exhibit a deceptively benign appearance microscopically. The finding of a linear or whorled array of spindled cells with few or no mitoses in a characteristic myxoid stroma can pose diagnostic dilemmas. Recurrences are common, and late metastases have been recorded. A closely related tumor, the so-called hyalinizing spindle cell tumor with giant collagen rosettes (HSCTGR), has also been described, with both the neoplasms having a similar cytogenetic abnormality and clinical behavior. Because of the similarities, both lesions are considered to be a single entity within the spectrum of low-grade sarcomas. Two cases of HSCTGR occuring in the lower limb are described in this report.

Lymphoepithelial Carcinomystery: A Curious Case of a Rare Parotid Tumor

Lymphoepithelial Carcinomystery: A Curious Case of a Rare Parotid Tumor

CORRECTION

An abstract that appeared on page 1319 of the September 2010 issue (Ciarlini PD, Sandhaus LM, Kidric DM, O'Riordan M. Automated cerebrospinal fluid cell counts using the Sysmex XE-5000: Is it time for new reference ranges? [CAP abstract 30, session 200] Arch Pathol Lab Med. 2010;134[9]:1319) included a financial interest disclosure that Dr. Linda M. Sandhaus received honoraria from Sysmex America, Inc, in support of her work on this abstract. The speaker honoraria Dr. Sandhaus received from Sysmex America, Inc, did not support the study described in the abstract.

Erupted cysts in the cervical esophagus result in gastric inlet patches

Gastric inlet patches (GIPs) are composed of islands of heterotopic gastric columnar epithelium in the cervical esophagus. They are often found accidentally at upper endoscopy with a reported prevalence of approximately 1% to 5%. 1 Akbayir N. Alkim C. Erdem L. et al. Heterotopic gastric mucosa in the cervical esophagus (inlet patch): endoscopic prevalence, histological and clinical characteristics. J Gastroenterol Hepatol. 2004; 19: 891-896 Crossref PubMed Scopus (69) Google Scholar , 2 Tang P. McKinley M.J. Sporrer M. et al. Inlet patch: prevalence, histologic type, and association with esophagitis, Barrett esophagus, and antritis. Arch Pathol Lab Med. 2004; 128: 444-447 PubMed Google Scholar However, symptoms such as globus sensations and other laryngeal and pharyngeal disorders have also been linked to their presence. 3 Von Rahden B.H. Stein H.J. et al. Heterotopic gastric mucosa of the esophagus: literature review and proposal of a clinicopathologic classification. Am J Gastroenterol. 2004; 99: 543-551 Crossref PubMed Scopus (136) Google Scholar This can be confirmed by our previously reported findings that ablation of the heterotopic gastric mucosa by means of argon plasma coagulation leads to resolution of such symptoms in the majority of all treated patients, 4 Meining A. Bajbouj M. Preeg M. et al. Argon plasma ablation of gastric inlet patches in the cervical esophagus may alleviate globus sensation: a pilot trial. Endoscopy. 2006; 38: 566-570 Crossref PubMed Scopus (47) Google Scholar in contrast to those treated by a sham procedure. 5 Bajbouj M. Becker V. Eckel F. et al. Argon plasma coagulation of cervical heterotopic gastric mucosa as an alternative treatment for globus sensations. Gastroenterology. 2009; 137: 440-444 Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar To date at our institution, there have been 41 patients treated. Among these, 37 (90.2%) were clinically followed. The overall success rate was 81% after a median follow-up of 21 months (range 3-54 months). Hence, ablation of the heterotopic mucosa appears to be beneficial for the majority of those patients.

Hypomethylation of the DNMT3L Promoter in Ocular Surface Squamous Neoplasia

N Context.—Cancer is known to have epigenetic inputs, with events like genomewide hypomethylation and genespecific hypermethylation of DNA. The DNA methyltransferase enzymes act as effectors of this reprogramming. A previous study revealed that hypomethylation at the DNA methyltransferase 3-like (DNMT3L) promoter could be a potential biomarker in cervical tumors. Because the pathobiology of ocular surface squamous neoplasia (OSSN) is similar to that of cervical tumors, we wanted to determine whether similar changes occur in the methylation pattern at the DNMT3L promoter in OSSN. Objective.—To evaluate the methylation status of the DNMT3L promoter in OSSN compared with healthy conjunctiva. Design.—We evaluated DNA methylation at the DNMT3L promoter in the tumor tissues of 6 patients with histologically proven OSSN and in healthy conjunctiva tissue from 7 individuals for controls using the sodium bisulfite–assisted conversion of genomic DNA. Extracted genomic DNA was treated with sodium bisulfite and amplified with specific primers for the DNMT3L promoter region. The specific polymerase chain reaction products were cloned and sequenced. Results.—The mean age of these patients was 50.2 years (range, 35–65 years). Histologically, 4 OSSN cases were invasive; 2 were intraepithelial. Healthy conjunctival tissues exhibited a methylated promoter region, whereas a variable loss of methylation was observed in all 6 OSSN cases. Conclusions.—We have, for the first time to our knowledge, identified loss of methylation at the DNMT3L promoter in OSSN cases, but its physiologic significance is yet to be understood. Further studies are warranted to substantiate our results. (Arch Pathol Lab Med. 2010;134:1193–1196)

Jejunal capillary hemangioma treated by using double-balloon endoscopy (with video)

Vascular tumors of the small bowel are rare, accounting for only 5% to 10% of all benign tumors of the small intestine. 1 Boyle L. Lack E.E. Solitary cavernous hemangioma of small intestine Case report and literature review. Arch Pathol Lab Med. 1993; 117: 939-941 PubMed Google Scholar , 2 Garvin P.J. Herrmann V. Kaminski D.L. et al. Benign and malignant tumors of the small intestine. Curr Probl Cancer. 1979; 3: 1-46 Abstract Full Text PDF PubMed Scopus (34) Google Scholar The main presenting symptom of capillary hemangioma is bleeding. In most cases, partial resections of the small bowel are necessary. Here, we report a rare case of capillary hemangioma of the small bowel treated by endoscopic mucosal resection by using double-balloon endoscopy (DBE).

Changes in the USP Heparin Monograph and Implications for Clinicians

Changes in the USP Heparin Monograph and Implications for Clinicians

Pathology of small airways disease.

N Context.—The term small airways disease encompasses a generally poorly understood group of lung diseases that may arise primarily within the small airways or secondarily from diseases primarily affecting the bronchi or lung parenchyma. Their histology may be confusing; however, because treatments and prognoses vary, correct pathologic diagnosis is important. Objective.—To present a nonexhaustive review of the pathology of primary and secondary small airways diseases, including small airways disease related to tobacco; to various other exposures, including mineral dusts; to diseases involving other areas of the lung with secondary bronchiolar involvement; and to recently described bronchiolitic disorders. Data Sources.—Current literature is reviewed. Conclusions.—Small airways diseases include a wide variety of diseases of which the pathologist must consider. Uncommon conditions such as diffuse idiopathic neuroendocrine cell hyperplasia and diffuse panbronchiolitis may show relatively specific diagnostic features histologically; however, most small airways diseases exhibit nonspecific histologic features. Conditions not considered primary pulmonary diseases, such as collagen vascular diseases, bone marrow transplantation, and inflammatory bowel disease, must also be considered in patients with small airways changes histologically. Clinical and radiologic correlation is important for obtaining the best possible diagnosis. (Arch Pathol Lab Med. 2010;134:702–718)

Immunohistochemical profile and fluorescence in situ hybridization analysis of diffuse large B-cell lymphoma in Northern China

N Context.—Gene expression profiling of diffuse large Bcell lymphoma using complementary DNA microarrays has revealed 2 major prognostic groups in Western countries: germinal center B-cell–like and nongerminal center B-cell– like lymphomas. Immunohistochemical analysis using antibodies specific for CD10, BCL6, and MUM1 has been proposed as a surrogate for gene expression profiling. Objective.—To study the immunohistochemical features of diffuse large B-cell lymphoma cases from northern China because geographic differences for this disease are known to exist. Design.—Morphologic, immunohistochemical, and fluorescence in situ hybridization analyses of 63 cases of diffuse large B-cell lymphoma from northern China. Results.—There were 38 men and 25 women with a median age of 57 years (range, 12–87 years). CD10 was positive in 19 cases (30%), BCL6 was positive in 22 cases (35%), and MUM1 was positive in 32 cases (51%). Twenty-one (33%) cases were germinal center B-cell–like lymphoma, and 42 (67%) were nongerminal center B-cell– like lymphoma. BCL2 was expressed more often in nongerminal center B-cell–like disease versus germinal center B-cell–like disease (60% versus 24%, P = .01) and in nodal versus extranodal (64% versus 30%, P = .01) cases. Fluorescence in situ hybridization analysis showed BCL6, MYC, and BCL2 rearrangements in 11 of 32 (34%), 8 of 27 (30%), and 11 of 50 (22%) cases, respectively. Conclusions.—These results add to what is known about the geographic variation of diffuse large B-cell lymphomas. In northern China, the frequency of the germinal center Bcell–like type and BCL6 expression and/or BCL6 rearrangement is less and the frequency of MYC rearrangement is greater than have been reported in Western countries. (Arch Pathol Lab Med. 2010;134:759–765)

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.

Sarcomatoid chromophobe renal cell carcinoma with heterologous sarcomatoid elements. A case report and review of the literature.

● Chromophobe renal cell carcinoma (CRCC) is a distinct subtype of renal cell carcinoma (RCC) that is well known for its relatively good prognosis. Sarcomatoid transformation in this tumor, although rare, has been well documented in the literature and, as in other types of RCC, carries an ominous prognosis for the patient. The finding of heterologous elements in the sarcomatoid component of CRCC is an extraordinary event, which has been reported in only 2 previous cases. Here, we present the third such case, occurring in the left kidney of a previously healthy 63-year-old woman. The nephrectomy specimen showed CRCC with extensive sarcomatoid changes displaying heterologous elements in the form of chondrosarcomatous and osteosarcomatous differentiation. As in other sarcomatoid RCCs, this tumor behaves aggressively, with frequent distant metastases. It is important to recognize the sarcomatoid component in these tumors because of its consequential adverse prognosis for the patient. (Arch Pathol Lab Med. 2009;133:1857‐1860)

Mitotic index of invasive breast carcinoma. Achieving clinically meaningful precision and evaluating tertial cutoffs.

● Context.—Mitotic figure counts are related to breast cancer behavior but have not been sufficiently reproducible to be accepted for clinical decision-making. Objective.—To improve reproducibility and accuracy of the mitotic count. Design.—Mitotic index (MI) was defined as the mitotic cell count per 10 high-power fields (HPFs), an area 0.183 mm 2 . Two to 6 replicate sets of 10 HPFs were counted from 328 invasive breast carcinomas. Standard errors and coefficients of variation for mean MI were compared with expected results predicted by the binomial distribution. Results.—The boundaries for MI that separated the data into equal thirds (tertials) were 1.14 and 5.33. Standard errors and coefficients of variation for MI followed distributions predicted by binomial probability. Mean coefficient of variation was 147% for the low tertial, 72% for the midtertial, and 34.6% for the upper tertial. Conclusions.—Standard errors for MI based on a single count of 10 HPFs are too broad and coefficients of variation too large to be acceptable for clinical use. This is explained as a binomial probability effect, possibly with a contribution from tumor heterogeneity. Errors can be reduced in proportion to the square root of the number of sets of 10 HPFs counted. Tertial cutoffs of MI of the Nottingham system currently used in breast carcinoma grading are too high to be applicable to the population we studied. We recommend validation of cutoffs before they are applied to a particular population of breast carcinomas. Counting 5 sets of 10 HPFs is necessary to accurately rank carcinomas with low MIs. (Arch Pathol Lab Med. 2009;133:1826–1833)

Primary intraosseous squamous cell carcinoma of the jaws. Clinicopathologic presentation and prognostic factors.

● Context.—Primary intraosseous squamous cell carcinoma is a rare form of squamous cell carcinoma, arising within the jaws. Objective.—To clarify the clinicopathologic and behavioral spectrum of primary intraosseous squamous cell carcinoma. Design.—The clinical and pathologic findings, treatment, and follow-up data of 39 cases of primary intraosseous squamous cell carcinoma were collected and analyzed. Results.—Of the 39 patients, 26 (67%) were men and 13 (33%) were women. The age at diagnosis ranged from 24 to 82 years (mean, 54 years). The tumors occurred predominantly (84.6%) in the posterior mandible. Microscopically, all tumors demonstrated general features of a squamous cell carcinoma; 19 of which (49%) also showed features suggestive of an odontogenic origin. The overall survival rates were 69.8% at 2 years and 36.3% at 5 years. Univariate analysis showed that tumors with or without odontogenic features, tumor grading, lymph node metastasis, and treatment modalities were significant prognostic factors for survival, but multivariate analysis showed that only histologic grading (relative risk, 4.43; P .03) remained a significant prognostic factor. The cumulative probabilities of recurrence were 55.7% at 2 years and 75.9% at 5 years. Univariate analysis showed that lymph node metastasis and treatment modalities were significant prognostic factors for recurrence. On multivariate analysis, however, only lymph node metastasis remained a significant prognostic factor (relative risk, 2.54; P .05). Conclusions.—Primary intraosseous squamous cell carcinoma is a high-grade malignancy with frequent, regional lymph node metastasis and high rates of recurrence and mortality. The tumor grading and regional lymph node metastasis may serve as useful indicators for prognosis. (Arch Pathol Lab Med. 2009;133:1834–1840)

Human Papillomavirus Typing and Viral Gene Expression Analysis for the Triage of Women With Abnormal Results From Papanicolaou Test Smears to Colposcopy

● Context.—A cascade of molecular tests for human papillomavirus (HPV), as a follow-up to Papanicolaou test screening, could eliminate unnecessary colposcopy. Tests based on detection of HPV E6 messenger RNA (mRNA) are already being used as screening tools, but there is a good biological rationale for expecting that an increase in the relative amounts of HPV E6 mRNA in cervical samples may better predict cancerous transformation. Objective.—To compare some of the available diagnostic methods and our novel method of relative quantification (RQ) of HPV gene expression for the effective triage of women with abnormal results from Papanicolaou tests to colposcopy. Design.—Sensitivities, specificities, and likelihood ratios were calculated for repeat Papanicolaou test smears, HPV DNA polymerase chain reactions, HPV genotyping, HPV16 E6 mRNA detection, and the RQ of HPV-16 E6 mRNA calibrated to cellular RNA and DNA levels and standardized to viral load. Results.—Human papillomavirus genotype in combination with a repeat Papanicolaou test can be used to categorize most women (96%) with cervical intraepithelial neoplasia of grade 2 or higher for colposcopy while eliminating 44% of women with cervical intraepithelial neoplasia 1 or less. The presence of HPV-16 E6 mRNA (P .001) and RQ of HPV-16 E6 mRNA (P .001) displayed significant median differences among the various grades of cervical intraepithelial neoplasia. Further testing of women who are positive for HPV-16 demonstrated that the RQ of E6 mRNA has diagnostic potential when combined with Papanicolaou testing in populations with higher disease prevalence. Conclusions.—The RQ of HPV E6 mRNA and HPV genotype could be useful in a cascade of diagnostic testing designed to refer women with findings of cervical abnormalities for colposcopy or treatment while reducing triage numbers. (Arch Pathol Lab Med. 2009;133:1577–1586)

Filariasis of the breast, diagnosed by fine needle aspiration cytology

Filariasis of the breast, diagnosed by fine needle aspiration cytology

Chronic lymphocytic leukemia cytoplasmic inclusions

American Journal of HematologyVolume 85, Issue 4 p. 275-276 Images in HematologyFree Access Chronic lymphocytic leukemia cytoplasmic inclusions† Namrata Setia, Namrata Setia Department of Pathology, Baystate Medical Center, Tufts University School of Medicine, Springfield, MassachusettsSearch for more papers by this authorTimothy Connolly, Timothy Connolly Department of Pathology, Baystate Medical Center, Tufts University School of Medicine, Springfield, MassachusettsSearch for more papers by this authorWilliam Levine, William Levine Department of Pathology, Baystate Franklin Medical Center, Tufts University School of Medicine, Springfield, MassachusettsSearch for more papers by this authorLiron Pantanowitz, Corresponding Author Liron Pantanowitz [email protected] Department of Pathology, Baystate Medical Center, Tufts University School of Medicine, Springfield, Massachusetts Department of Pathology, Baystate Franklin Medical Center, Tufts University School of Medicine, Springfield, MassachusettsDepartment of Pathology, Baystate Medical Center, 759 Chestnut Street, Springfield, MA 01199Search for more papers by this author Namrata Setia, Namrata Setia Department of Pathology, Baystate Medical Center, Tufts University School of Medicine, Springfield, MassachusettsSearch for more papers by this authorTimothy Connolly, Timothy Connolly Department of Pathology, Baystate Medical Center, Tufts University School of Medicine, Springfield, MassachusettsSearch for more papers by this authorWilliam Levine, William Levine Department of Pathology, Baystate Franklin Medical Center, Tufts University School of Medicine, Springfield, MassachusettsSearch for more papers by this authorLiron Pantanowitz, Corresponding Author Liron Pantanowitz [email protected] Department of Pathology, Baystate Medical Center, Tufts University School of Medicine, Springfield, Massachusetts Department of Pathology, Baystate Franklin Medical Center, Tufts University School of Medicine, Springfield, MassachusettsDepartment of Pathology, Baystate Medical Center, 759 Chestnut Street, Springfield, MA 01199Search for more papers by this author First published: 16 July 2009 https://doi.org/10.1002/ajh.21502Citations: 1 † Conflict of interest: Nothing to report. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1 McCann SR,Whelan A,Greally J. Intracellular lambda light chain inclusions in chronic lymphocytic leukaemia. Br J Haematol 1978; 38: 367– 371. 2 Ralfkiaer E,Hou-Jensen K,Geisler C, et al. Cytoplasmic inclusions in lymphocytes of chronic lymphocytic leukaemia. A report of 10 cases. Virchows Arch A Pathol Anat Histol 1982; 395: 227– 236. 3 Berrebi A,Talmor M,Vorst E, et al. IgM lambda globular cytoplasmic inclusions in chronic lymphocytic leukaemia resembling immunocytoma. Scand J Haematol 1983; 30: 43– 49. 4 Dorion RP,Shaw JH. Intracytoplasmic filamentous inclusions in the peripheral blood of a patient with chronic lymphocytic leukemia. A bright-field, electron microscopic, immunofluorescent, and flow cytometric study. Arch Pathol Lab Med 2003; 127: 618– 620. 5 Djaldetti M,Eisbruch A,Perek J,Hart J. Cytoplasmic inclusions and X-ray microprobe analysis in a case of prolymphocytic leukemia. J Cancer Res Clin Oncol 1984; 107: 229– 232. Citing Literature Volume85, Issue4April 2010Pages 275-276 ReferencesRelatedInformation

Undiagnosed Type IIIc Gaucher Disease in a Child With Aortic and Mitral Valve Calcification: Perioperative Complications After Cardiac Surgery

GAUCHER DISEASE, the most common form of lysosomal storage disease, is caused by an inherited deficiency of the β-glucocerebrosidase enzyme. Pathology results from the accumulation of glucocerebroside in the reticuloendothelial system; Gaucher disease generally manifests as 1 of 3 clinical variants: type I, type II, and type III. 1 Jmoudiak M. Futerman A.H. Gaucher disease: Pathological mechanisms and modern management. Br J Haematol. 2005; 129: 178-188 Crossref PubMed Scopus (229) Google Scholar , 2 Chen M. Wang J. Gaucher disease: Review of the literature. Arch Pathol Lab Med. 2008; 132: 851-853 PubMed Google Scholar , 3 Grabowski G. Recent clinical progress in Gaucher disease. Curr Opin Pediatr. 2005; 17: 519-524 Crossref PubMed Scopus (56) Google Scholar Type I (adult, chronic, nonneuronopathic) is the most common and mildest form. Patients often present with hepatosplenomegaly and a combination of anemia, thrombocytopenia, and leucopenia. They may have skeletal disease including osteopenia and Erlenmeyer flask deformity of the distal femur. A small number of type I patients develop interstitial lung disease and pulmonary hypertension. 1 Jmoudiak M. Futerman A.H. Gaucher disease: Pathological mechanisms and modern management. Br J Haematol. 2005; 129: 178-188 Crossref PubMed Scopus (229) Google Scholar Patients with type II (infantile, acute, neuronopathic) have severe neurologic abnormalities; it is usually fatal within 2 years. Patients with type III (juvenile, subacute, neuronopathic) exhibit slowly progressive neurologic symptoms, including seizures and oculomotor apraxia that start in childhood or early adult life.

Notice of retraction: omission of author in "Malakoplakia outside the urinary tract" (Arch Pathol Lab Med. 2007;131(2):297-300).

Notice of retraction: omission of author in "Malakoplakia outside the urinary tract" (Arch Pathol Lab Med. 2007;131(2):297-300).

Unknown primary cancer (UPC): Accuracy of tissue of origin prediction by molecular profiling

11070 Background: Molecular profiling may be useful to identify the primary site and direct therapy for patients (pts) with UPC. Since most UPC pts never have a primary site identified, the accuracy of molecular profiling diagnoses are difficult to verify. We identified a group of UPC pts who had a primary site subsequently identified during their clinical course, and performed a 92-gene real time polymerase chain reaction (RT-PCR) assay (Arch Pathol Lab Med 130:465, 2006) on tissue from the initial diagnostic biopsy. We then compared the RT-PCR diagnosis with the subsequent clinical diagnosis. Methods: 38 of 501 UPC pts (7%) seen between 2000 and 2008 had their primary tumor subsequently identified during life. 24 of the 38 pts had tissue biopsies (excluding FNA cytology) and are the subject of this study. The RT-PCR assay was performed on unstained slides from the formalin-fixed, paraffin-embedded (FFPE) initial diagnostic biopsy, and the assay predictions were compared to the actual primary sites (found later). No clinical or pathologic data (other than sex, biopsy site, and 1 H&E stained slide) were used in the prediction of the primary site. Results: 16 of 24 assays were successful (8 had no tumor or RNA in the material). 11 of 16 predictions of the site of origin (68%) were correct, corresponding to the actual primary sites found 3–58 months (median 8.5 months) after the initial diagnosis of UPC. Primary sites correctly identified included breast 2, ovary/peritoneal 4, NSCLC 1, colorectal 2, gastric 1, melanoma 1. 3 predictions were inaccurate (colorectal, testicular, sarcoma) in patients with gastroesophageal, pancreas and NSCLC, respectively. 2 assays were unclassifiable. Conclusions: RT-PCR performed on FFPE initial diagnostic tissue was accurate in predicting the primary site of origin in 11 of 16 pts with UPC who eventually had their primary site identified clinically. These data provide a direct validation of the reliability of this RT-PCR assay in predicting the primary site in pts with UPC. When used in concert with clinical features and IHC stains, molecular profiling may provide the basis for more successful site-directed therapy for many of these pts. Prospective studies of RT-PCR in UPC are ongoing. [Table: see text]