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Martinez-Escala M.E.,Northwestern University | Sidiropoulos M.,Northwestern University | Deonizio J.,Northwestern University | Gerami P.,Northwestern University | And 3 more authors.
British Journal of Dermatology | Year: 2015

Background T cells with a γδ phenotype have been associated with aggressive lymphomas. Yet, inflammatory skin disorders and low-grade lymphoproliferative disorders have rarely been described with a predominant γδ T-cell infiltrate. Objectives To review our experience and determine the clinical relevance of the γδ T-cell phenotype in lymphomatoid papulosis (LyP) and pityriasis lichenoides (PL). Methods A retrospective dermatopathology file review looking for LyP and PL characterized by a γδ T-cell phenotype was performed. Clinical manifestations and course, histological features and molecular data were analyzed. Results Six of 16 cases of LyP and four of 23 cases diagnosed as PL during a 5-year period (2009-14) were identified. The median follow-up for the whole group was 16 months (range 3-64), showing an indolent clinical course in all cases. Conclusions The detection of a predominantly γδ T-cell phenotype in papular lymphoid-rich infiltrates in the absence of other lesions is not associated with a clinically aggressive course. γδ T-cell-rich variants of LyP and PL may reflect a spectrum of related conditions. This is a single academic centre retrospective chart review of a relatively small sample. © 2014 British Association of Dermatologists.

Khan S.A.,Lynn Sage Breast Center | Mangat A.,Lynn Sage Breast Center | Rivers A.,Beaumont Breast Center | Revesz E.,Lynn Sage Breast Center | And 2 more authors.
Annals of Surgical Oncology | Year: 2011

Background: Pathologic nipple discharge (PND) is diagnosed clinically and managed by diagnostic duct excision (DDE). Mammary ductoscopy in the office setting may change this standard. We performed a prospective study to assess the utility of office ductoscopy for surgical selection in women with nipple discharge. Methods: Women with nipple discharge meeting at least 2 of 3 criteria of PND (spontaneous, single duct, bloody or serous) underwent office ductoscopy. Those showing papillomatous lesions underwent DDE in the operating room (surgical group, n = 38); if no lesion was present, women were followed clinically (observation group, n = 21). Results: A papillomatous lesion was identified in 79% of women with 3-criteria PND and in 21% with 2 criteria (P = .001). DDE yielded a proliferative lesion in 35 of 38 women (92%). Of the 38, 27 (71%) had papillomata, 2 (5%) had florid hyperplasia, and 6 (16%) had ductal carcinoma in situ (DCIS) on final pathology. Also, 11 women with papilloma and 1 with DCIS presented with 2-criteria PND. Ductoscopy findings were a better predictor of the presence of intraductal neoplasia (area under curve [AUC] 0.9, 95% confidence interval [95% CI] 0.8-0.98) compared with 3-criteria PND (AUC 0.7, 95% CI 0.6-0.8). The 21 women in the observation group did not develop signs of malignancy or need biopsy during a 48-month follow-up period. Conclusions: Our findings suggest that office ductoscopy provides accurate surgical selection of women with nipple discharge and should be considered for women with 2 criteria of PND, and those with negative ductoscopy can be safely observed. These findings need confirmation in a larger study with longer follow-up. © 2011 Society of Surgical Oncology.

Shinnick K.M.,Feinberg Cardiovascular Research Institute | Shinnick K.M.,Robert rie Cancer Center | Eklund E.A.,Robert rie Cancer Center | Eklund E.A.,Jesse Brown Medical Center | And 2 more authors.
Journal of Clinical Investigation | Year: 2010

HSCs maintain the circulating blood cell population. Defects in the orderly pattern of hematopoietic cell division and differentiation can lead to leukemia, myeloproliferative disorders, or marrow failure; however, the factors that control this pattern are incompletely understood. Geminin is an unstable regulatory protein that regulates the extent of DNA replication and is thought to coordinate cell division with cell differentiation. Here, we set out to determine the function of Geminin in hematopoiesis by deleting the Geminin gene (Gmnn) from mouse bone marrow cells. This severely perturbed the pattern of blood cell production in all 3 hematopoietic lineages (erythrocyte, megakaryocyte, and leukocyte). Red cell production was virtually abolished, while megakaryocyte production was greatly enhanced. Leukocyte production transiently decreased and then recovered. Stem and progenitor cell numbers were preserved, and Gmnn-/- HSCs successfully reconstituted hematopoiesis in irradiated mice. CD34+ Gmnn-/- leukocyte precursors displayed DNA overreplication and formed extremely small granulocyte and monocyte colonies in methylcellulose. While cultured Gmnn-/- megakaryocyte-erythrocyte precursors did not form erythroid colonies, they did form greater than normal numbers of megakaryocyte colonies. Gmnn-/- megakaryocytes and erythroblasts had normal DNA content. These data led us to postulate that Geminin regulates the relative production of erythrocytes and megakaryocytes from megakaryocyte-erythrocyte precursors by a replication-independent mechanism.

Gerami P.,Robert rie Comprehensive Cancer Center | Gerami P.,Robert rie Cancer Center | Busam K.,Sloan Kettering Cancer Center | Cochran A.,University of California at Los Angeles | And 19 more authors.
American Journal of Surgical Pathology | Year: 2014

Predicting clinical behavior of atypical Spitz tumors remains problematic. In this study, we assessed interobserver agreement of diagnosis by 13 expert dermatopathologists for atypical Spitz tumors (n=75). We determined which histomorphologic features were most heavily weighted for their diagnostic significance by the experts and also which histomorphologic features had a statistically significant correlation with clinical outcome. There was a low interobserver agreement among the experts in categorizing lesions as malignant versus nonmalignant (κ=0.30). The histomorphologic features that were given the most diagnostic significance by the experts were: consumption of the epidermis, atypical mitoses, high-grade cytologic atypia, and mitotic rate. Conversely, the histomorphologic features that most correlated with disease progression were: frequent mitoses, deep mitoses, asymmetry, high-grade cytologic atypia, and ulceration. The presence and/or pattern of pagetoid spread, consumption of the epidermis, and lymphoid aggregates demonstrated no association with clinical behavior. The results support the assertion that there is a lack of consensus in the assessment of atypical Spitz tumors by expert dermatopathologists. Importantly, many features used to distinguish conventional melanoma from nevi were not useful in predicting the behavior of atypical Spitz tumors. This study may provide some guidance regarding histologic assessment of these enigmatic tumors. Copyright © 2014 by Lippincott Williams & Wilkins.

Yelamos O.,Northwestern University | Arva N.C.,Ann and Robert H. Lurie Childrens Hospital of Chicago | Obregon R.,Northwestern University | Yazdan P.,Northwestern University | And 5 more authors.
American Journal of Surgical Pathology | Year: 2015

Differentiating proliferative nodules (PNs) from melanomas arising in congenital nevi (CN) is a considerable challenge for dermatopathologists. Most of the specimens dermatopathologists assess that deal with this differential diagnosis involve proliferations of melanocytes arising in the dermis. In this study, we compare the clinical, histologic, and molecular findings of these 2 conditions. In our database, we found 22 examples of PNs arising in the dermis of CN and 2 cases of lethal melanomas arising from the dermis/epidermis of CN of children. Importantly, we found that among dermal melanocytic proliferations arising from CN in children, PNs are far more common than lethal melanomas. Clinically, multiplicity of lesions favored a diagnosis of PNs, whereas ulceration was infrequent in PNs compared with lethal melanomas. Histologically, PNs showed several distinct patterns including expansile nodules of epithelioid melanocytes with mitotic counts lower than that seen in the melanomas (1.67 vs. 12.5 mitoses/mm 2), a small round blue cell pattern often highly mitotically active, neurocristic-like, blue nevus-like, a nevoid melanoma-like pattern, or an undifferentiated spindle cell pattern. The lethal melanomas both featured expansile nodules of epithelioid melanocytes with high mitotic counts (range, 5 to 20 mitoses/mm 2) and an ulcerated overlying epidermis. At the molecular level, the PNs showed mostly whole chromosomal copy number aberrations, which in some cases were accompanied by rare partial chromosomal aberrations, whereas both lethal melanomas showed highly elevated copy number aberrations involving 6p25 without gains of the long arm of chromosome 6. Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.

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