ARCHIVES of & Laboratory Medicine

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Table 1. Histopathologic Characteristics and Human Papillomavirus (HPV) Genotyping Resultsa Growth HPV Case No. Pattern Koilocytosis Associated SIL (DNA Chip) HPV PCR HPV (Real-Time PCR) 1 Exophytic HSIL 16 ND ND 2 Exophytic þ HSIL 16, 18 ND ND Color 3 Flat � Neg Neg 42 4 Exophytic ��11 ND ND 5 Exophytic þ�HPV, unclassified ND ND 6 Flat þ�HSIL Neg Neg Not amplified 7 Exophytic � Neg Neg Neg 8 Exophytic ��Neg Neg Not amplified 9 Exophytic þ�11 ND ND 10 Flat þ�Neg Neg 6 11 Exophytic þ�11 ND ND 12 Exophytic ��11 ND ND 13 Exophytic þ�6 ND ND 4-color 1,000 þ� 14 Exophytic 11 ND ND 15 Flat þ�HSIL 11 ND ND 16 Exophytic � Neg LR-HPV 6 17 Exophytic þ�11 ND ND 18 Exophytic ��6 ND ND 19 Exophytic ��6 ND ND 20 Exophytic ��HSIL Neg Neg 33 21 Exophytic � Neg Neg Neg 22 Exophytic ��HSIL Neg LR-HPV 6 23 Exophytic þ Neg LR-HPV 6 24 Exophytic þ�11 ND ND 25 Flat þ�HSIL ND ND 6, 16 26 Exophytic þ HSIL ND ND 11, 58 þ Abbreviations: HSIL, high-grade squamous intraepithelial lesion; LR-HPV, low-risk human papillomavirus types; ND, not done; Neg, negative; PCR, 2nd color polymerase chain reaction; SIL, squamous intraepithelial lesion; , present; , absent. þ � a All cases disclosed nonblock positivity for p16INK4a.

Immunohistochemical Expression index between PIM and HSILs was well demonstrated in the same specimen (Figure 2, B). The Ki-67 labeling index of PIM ranged from 10% to 56% INK4a matched from 500 (mean, 24%), which exceeded that of the normal squamous p16 staining showed patchy, nonblock positivity in all epithelium, but was significantly lower than that of HSIL PIM cases with various intensities (Figure 2, C; and open (range, 64%–92%; mean, 79%; P , .001). The Ki-67 arrow), but the basal and parabasal layers were mostly immunostaining showed basal/parabasal positivity with spared. The HSILs in the adjacent mucosa (Figure 2, B; and upward extension in 24 cases (Figure 2, B; and open arrow), closed arrow) and the 14 HSILs included as the control process but in 2 of 5 cases forming a flat-topped plaque, Ki-67 group demonstrated extensive and strong reactivity in the labeling index was significantly decreased in basal/parabasal entire layers or in the basal and parabasal cells layers. layers as well as in the upper epithelium. Papillary lesion CK17 was normally expressed in the cytoplasm of the with prominent koilocytosis showed significantly increased subcolumnar reserve cell layer and immature squamous Ki-67 positivity in the upper epithelium in addition to the (Figure 3, A), but not in the apically located basal/parabasal positivity (Figure 2, B; and open arrow); in mucin-containing columnar epithelium and mature, or contrast, the Ki-67–labeled cells were confined to the atrophic, squamous epithelia. In PIM, CK17 reactivity was parabasal and/or basal cell layers in normal or atrophic exclusively found only in the basal layers in 10 of the 26 squamous epithelia. The difference in the Ki-67 labeling cases (38%) or in both the basal and parabasal layers in 14 Benign Mesothelial Cells (Left) Showing 2 Signals of Chromosomes 3 (Red), 7 (Green), and 17 (Blue), and of the 9p21 Band (Yellow); 4 Signals Shown in Proliferating Cells 5th color Indicates Tetraploidization. Malignant Mesothelioma Cells (Right) Show Homozygous 750 Deletion of p16 With Loss of Both 9p21 Signals (Lost Yellow Signal) August 2018 Figure 1. Papillary immature metaplasia forming either an exophytic mass of filiform papillae (A) or a flat-topped lesion with the predominantly inverted growth of rete pegs (B). The lesional epithelium consists of a thick layer of proliferating basaloid and immature metaplastic cells (C), a or Pantone variable proportion of which are mature. The mucinous epithelium is demonstrable, and linearly aligned atop the immature or mature squamous epithelium by alcian blue (D and E, arrows). Sometimes it forms glandular structures within the squamous epithelium (A and F, arrows) or is th individually scattered within the nested squamous cells (E, arrows). are found exclusively in the mature squamous cells (E and F) Biennial) Meeting of the Pulmonary (hematoxylin-eosin, original magnifications 340 [A, B, and F] and 3200 [C]; alcian blue, original magnifications 3100 [D] and 3200 [E]). Special Sections—2017 (10 Figure 2. A flat high-grade squamous intraepithelial lesion (HSIL) lies in direct continuity with the mucosa adjacent to the papillary immature Pathology Society, Part I; KOPANA 2017 Spring Seminar, Part II metaplasia (PIM) (A); however, PIM (open arrow) and HSIL (closed arrow) are easily distinguishable owing to the different degrees of cytologic atypia (A), Ki-67 labeling index in PIM (open arrow) and HSIL (closed arrow) (B), and different p16INK4 expression patterns in PIM (open arrow) and HSIL (closed arrow) (C) (hematoxylin-eosin, original magnification 340 [A]; original magnification 340 [B and C]). Ads produced with combinations 976 Arch Pathol Lab Med—Vol 142, August 2018 Papillary Immature Metaplasia of Uterine Cervix—Hong et al Arch Pathol Lab Med—Vol 142, August 2018 Papillary Immature Metaplasia of Uterine Cervix—Hong et al 977 of process inks (cyan, magenta, yellow, and black) use color most economically. Many Pantone (PMS) Advertising Directors Publisher/Sales Offi ce specifi ed colors can often be East: Hally Birnbaum Bob McGonnagle approximated using process inks. Mount Kisco, NY 325 Waukegan Road, Northfi eld, IL 60093 Call Keith Eilers, 847-832-7528, Phone: 914-218-1943; Fax: 847-832-8153 Phone: 847-832-7476; Fax: 847-832-8153 with questions about color use. [email protected] [email protected] Insertion Rates Full-run insert rates Midwest: Lori Prochaska Advertising Materials are generally the B/W page rate times Omaha, NE Keith Eilers, Ad Materials Manager the number of insert pages. Please Phone: 402-290-7670; Fax: 847-832-8153 325 Waukegan Road, Northfi eld, IL 60093 call for a specifi c quotation. [email protected] Phone: 847-832-7528; Fax: 847-832-8528 [email protected] West: Diana Kelker Sacramento, CA Classifi ed Phone: 847-832-7749; Fax: 847-832-8749 KERH Group, PO Box 207, Parker Ford, PA 19457 [email protected] Phone: 888-489-1555, [email protected] 2019 Bonus Distribution at important pathology shows: USCAP (March–Washington DC); ASCO (June–Chicago); CAP19 (September–Orlando); AMP (November–Baltimore); ASH (December–Orlando) You should advertise in the Anaplastic Lymphoma Kinase Gene Rearrangement by Fluorescence In Situ Archives of Pathology & Laboratory Medicine if: Hybridization in Non-Small Cell Lung Cancer on Direct Smears March 2018 Special Section—Updated CAP, IASLC, and AMP Molecular Lung Pathologists are important targets for your JANUARY 2018 ◆ ◆ LABORATORY MANAGEMENT Cancer Testing Guideline; Updates From the 2016 Molecular PATHOLOGY LABORATORY MEDICINE Meeting (Napoli, Italy), Part I

Clin Lab 2.0: Add value, make patients“The value discussion has better been underway for Anne Paxton meeting in March 2016 as “Project Santa Fe.” They some years,” says founding member James Craw- services and products see their concept of Clinical Laboratory 2.0, empha- ford, MD, PhD, senior vice president of laboratory It was baseball’s Yogi Berra who said, with the sizing demonstration of how the laboratory adds unique slant that was his hallmark, “In theory there services at Northwell Health in the greater New York value to patient care, as a critical clinical and busi- metropolitan area. “Project Santa Fe was founded to is no difference between theory and practice. In —continued on 18 ness model for re-engineering laboratories’ role in bring together like-minded practice, there is.” More vividly, boxer Mike Tyson the health care system. once summed up the same reality when asked to comment on an opponent’s strategy Next-gen sequencing in an upcoming match: “Everybody has a plan—until they get hit.” fi nds further clinical Your therapeutic drugs are tied to tests Altman Jennifer Laboratories may not have to fear utility in oncology such a sudden and traumatic hour of William Check, PhD reckoning. But as new payment mod- One of the plenary sessions at the els change volume-based health care 2017 meeting of the Association for to value-based health care, these sports Molecular Pathology—“High Impact lessons are relevant to the laboratory for Cancer industry’s strategic planning. If add- and Inherited ”—was a vir- establishing personalized diagnostics ing value, in theory, is becoming es- tual mini-course in the latest and sential to laboratories’ survival, what All advertising earns most useful applications of next- does that mean they should do, in generation sequencing to detect practical terms? To explore the next era for health germline and somatic mutations in cancer. Both speakers zeroed in on care and what it means for labs, CEOs the clinical utility of their innovative and directors from Geisinger Health, diagnostic techniques. a combined rate based Henry Ford Health System, North- You value smart media buying* A. John Iafrate, MD, PhD, ad- well Health Laboratories, Kaiser Per- dressed the expanding use of NGS to manente North Laboratories, and guide targeted therapies in lung can- TriCore Reference Laboratories began cer. Dr. Iafrate, a pathologist at Mas- Dr. James Crawford (right) with (from left) Reeti Khare, sachusetts General Hospital, medical PhD, assistant director of infectious diagnostics; director of its Center for Integrated on the total number Tarush Kothari, MD, MPH, physician informaticist; and Diagnostics, and a professor at Har- Yehuda Jacobs, software architect. The question Dr. vard Medical School, focused on Crawford asks his laboratory colleagues is, “Can you The Archives is received by 88% of pathologists detecting the —continued on 42 demonstrate that patients are better for having received care from your lab as opposed to from other labs?” of ad units in the Genotype-guided dosing of warfarin: ofGIFT whether genotype-guidedwrap-up warfarin Despite GIFT showing that geno- Elizabeth Silverman dosing provided statistically signifi - type-guided dosing prevents more In an ideal world, clinical research cant clinical benefi t to patients under- adverse outcomes than clinically The Archives is read by 67% of pathologists data would be applied with immedi- going anticoagulant therapy. The in- guided dosing, pharmacogenetic test- ate and beneficial effect to clinical consistent results of —continued on 47 Archives of Pathology ing to improve warfarin initiation practice, especially when the data may not become wide- come from a well-controlled, well-run spread practice anytime trial that meets the gold standard of soon. being large, randomized, and blind- 847-832-8153. : GIFT was designed to ed. However, as the Sept. 26 publica-

do what the earlier CAP TODAY

Fax a copy of the below the of copy a Fax CAP TODAY CAP and . tion of the Genetic Informatics Trial to The Archives provides ad exposure to 38% of pathologists COAG and EU-PACT evaluate genotype-guided dosing of trials had failed to do: warfarin demonstrates, reality is far provide the definitive more complicated (Gage BF, et al. answer to the question JAMA. 2017;318[12]:1115–1124).

Sara Enders and Steven Cotten, PhD address with corrections to to corrections with address *Kantar Media Readership Survey of Pathologist Publications 2017 1 No. 32, Vol. Moving? POC glucose testing in the criticallyPage 10ill Lab options, latest studies, one lab’s program

1/9/18 3:42 PM

0118_1-48_SantaFe-MolecDx-Gift_2.indd 1

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A The Archives eToC e-blast eTOC banner notifi cations reach at least 15,000 Print advertisers can Frequency Monthly pathologists per mailing. Print E-direct advertisers have the option of e-blast their branded Rate $1,200 Rate $3,100 message to at least adding a banner above this monthly 15,000 pathologists Size 468 × 120 pixels e-blast notifi cation. The e-blast Size max width 600 pixels selected from the recipients will be redirected to CAP email list. Format jpg view the latest Archives issue at Format html and text version www.archivesofpathology.org. Deadline: 25th of month Deadline: 7 days prior to mail date prior to publication

Contact your Advertising Director for availability. Send materials to: Keith Eilers 847-832-7528 [email protected] East: Hally Birnbaum 914-218-1943 [email protected] | Midwest: Lori Prochaska 402-290-7670 [email protected] | West: Diana Kelker 847-832-7749 [email protected]