Atif Saleem

All Publications

• Diagnostic Utility of LEF1 Immunohistochemistry in Differentiating Deep Penetrating Nevi From Histologic Mimics. The American journal of surgical pathology Raghavan, S. S., Saleem, A., Wang, J. Y., Rieger, K. E., Brown, R. A., Novoa, R. A. 2020

  Abstract

  Deep penetrating nevi (DPNs) are intermediate grade lesions which have the capacity to recur, metastasize, or progress to melanoma. Differentiating DPN from other melanocytic lesions including blue and cellular blue nevi can be diagnostically challenging, and markers to distinguish these entities can be useful. Mutations of the beta-catenin and mitogen-activated protein kinase pathways have recently been elucidated as distinctive of DPN. This pathway can subsequently activate lymphoid enhancer-binding factor 1 (LEF1), a transcription factor shown to facilitate the epithelial-mesenchymal transition to propagate tumorigenesis. Seventy-two cases in total were examined on hematoxylin and eosin sections and with beta-catenin and LEF1 immunohistochemistry. This included: DPN (14), cellular blue nevi (19), blue nevi (15), congenital melanocytic nevi (12), and melanoma (12). Nuclear expression of LEF1, present throughout the entire depth of the lesion, was noted in 13/14 (93%) of DPN, 0/19 (0%) of cellular blue nevi, 0/15 (0%) of blue nevi, 1/12 (8%) of congenital melanocytic nevi, and 9/12 (75%) of melanoma cases. Nuclear expression of beta-catenin, present throughout the entire depth of the lesion, was noted in 14/14 (100%) of DPN, 0/18 (0%) of cellular blue nevi, 0/15 (0%) of blue nevi, 1/12 (8%) of congenital melanocytic nevi, and 1/12 (8%) of melanoma cases. A majority of congenital melanocytic nevi demonstrated a gradient of LEF1 and beta-catenin expression with more intense staining superficially and loss of staining with increasing depth. Deep, uniform nuclear LEF1 combined with beta-catenin immunohistochemical staining can be useful in distinguishing DPN from histologic mimics.

  View details for DOI 10.1097/PAS.0000000000001513

  View details for PubMedID 32520758

• Expansion of Bone Precursors through Jun as a Novel Treatment for Osteoporosis-Associated Fractures. Stem cell reports Lerbs, T., Cui, L., Muscat, C., Saleem, A., van Neste, C., Domizi, P., Chan, C., Wernig, G. 2020

  Abstract

  Osteoporosis and osteoporotic fractures lead to decreased life quality and high healthcare costs. Current treatments prevent losses in bone mass and fractures to some extent but have side effects. Therefore, better therapies are needed. This study investigated whether the transcriptionfactor Jun has a specific pro-osteogenic potency and whether modulating Jun could serve as a novel treatment for osteoporosis-associated fractures. We demonstrate that ectopically transplanted whole bones and distinct osteoprogenitors increase bone formation. Perinatal Jun induction disturbs growth plate architecture, causing a striking phenotype with shortened and thickened bones. Molecularly, Jun induces hedgehog signaling in skeletal stem cells. Therapeutically, Jun accelerates bone growth and healing in a drilling-defect model. Altogether, these results demonstrate that Jun drives bone formation by expanding osteoprogenitor populations and forcing them into the bone fate, providing a rationale for future clinical applications.

  View details for DOI 10.1016/j.stemcr.2020.02.009

  View details for PubMedID 32197115

• Is Merkel Cell Carcinoma of Lymph Node Actually Metastatic Cutaneous Merkel Cell Carcinoma? American journal of clinical pathology Lawrence, L. E., Saleem, A., Sahoo, M. K., Tan, S. K., Pinsky, B. A., Natkunam, Y., Kunder, C. A., Stehr, H., Zehnder, J. L. 2020

  Abstract

  The possibility of a so-called primary lymph node neuroendocrine carcinoma has been described in the literature. Here we evaluate cases fitting such a diagnosis and find that the cases demonstrate a convincing and pervasive pattern consistent with metastatic Merkel cell carcinoma.Six cases of primary lymph node Merkel cell carcinoma and one case of metastatic neuroendocrine carcinoma at a bony site, all with unknown primary, were sequenced using a combination of whole-exome and targeted panel methods. Sequencing results were analyzed for the presence of an ultraviolet (UV) mutational signature or off-target detection of Merkel cell polyomavirus (MCPyV).Four of six primary lymph node cases were positive for a UV mutational signature, with the remaining two cases positive for off-target alignment of MCPyV. One case of neuroendocrine carcinoma occurring at a bony site was also positive for a UV mutational signature.We find no evidence to corroborate the existence of so-called primary Merkel cell carcinoma of lymph node.

  View details for DOI 10.1093/ajcp/aqaa051

  View details for PubMedID 32445471

• Extranodal NK/T-Cell Lymphomas: The Role of Natural Killer Cells and EBV in Lymphomagenesis. International journal of molecular sciences Saleem, A., Natkunam, Y. 2020; 21 (4)

  Abstract

  Keywords: NK cells, extranodal NK/T-cell lymphoma, EBV.

  View details for DOI 10.3390/ijms21041501

  View details for PubMedID 32098335

• Fungal prostatitis due to endemic mycoses and Cryptococcus: A multicenter case series. The Prostate Epstein, D. J., Thompson, L. D., Saleem, A., Kao, C. S., Epstein, J. I. 2020

  Abstract

  Fungal prostatitis is exceedingly rare with mostly case reports.Electronic medical records at three medical centers were searched for cases of fungal prostatitis due to endemic mycoses and Cryptococcus over the preceding 10 years.Seven cases were identified from 105?600 prostate biopsies within the Southern California Permanente Medical Group for an incidence of 0.0066%. An additional eight cases were identified from two other health care systems. Excluding four patients without available clinical data, 11 patients were reviewed, most of whom underwent biopsy due to elevated prostate-specific antigen. Four were asymptomatic and the remainder had nonspecific signs or symptoms. All biopsies revealed granulomatous inflammation and fungal organisms. Seven patients had coccidioidomycosis, three patients had cryptococcosis (confirmed in two cases and suspected by organism morphology in the other), and one patient had likely histoplasmosis based on organism morphology. Prolonged antifungal treatment was standard; outcomes were favorable.Fungal prostatitis due to endemic mycoses and Cryptococcus is uncommon and associated with favorable outcomes but generally involves prolonged therapy.

  View details for DOI 10.1002/pros.24034

  View details for PubMedID 32572997

• Novel IRF8 and PD-L1 molecular aberrations in systemic EBV-positive T-cell lymphoma of childhood Human Pathology: Case Reports Volume 19, March 2020, 200356 Saleem, A., Joshi, R., Lei, L., Lezama, L., Raghavan, S. S., Neishaboori, N., Roy, M., Schroers-Martin, J., Charville, G. W., Kunder, C., Tan, B., Martin, B. A., Natkunam, Y. 2020; 19
• Non-HLA Antibody-Mediated Rejection of Lung Transplant Masquerading Transfusion-Related Acute Lung Injury Yunce, M., Virk, M., Zhang, B. M., Mooney, K., Saleem, A., Shan, H. WILEY. 2019: 199A

  View details for Web of Science ID 000502826600470

• Intralymphatic Rosai-Dorfman Disease Associated With Vulvar Lymphedema: A Case Report of an Extremely Rare Phenomenon. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists Saleem, A., Hoffmann, J., Warnke, R., Rieger, K. E., Longacre, T. 2019

  Abstract

  Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease (RDD), is a self-limited histiocytic disorder of unclear etiology which most commonly presents with cervical lymphadenopathy. Purely extranodal presentation of RDD is uncommon, and isolated intralymphatic/intravascular confinement of this entity has not previously been described. We report a 16-yr-old female who presented with vaginal swelling and mass-like enlargement of the right labia. The mass had been present for nearly a year without pain or tenderness. Clinically, the lesion was thought to be a Bartholin gland cyst. Following surgical resection, histologic examination demonstrated a hypocellular myxedematous stroma with a mixture of ectatic thin and thick-walled vessels within which there were numerous collections of histiocytes, lymphocytes, and plasma cells. The histopathologic differential diagnosis included localized vulvar lymphedema, a specialized genital tract neoplasm, and childhood asymmetric labium majus enlargement. The histiocytes showed occasional plasma cells and lymphocytes within their cytoplasm, consistent with emperipolesis. Immunohistochemical studies showed that the histiocytes expressed CD163 and S100, while ERG and D2-40 highlighted their intralymphatic confinement, ultimately leading to the diagnosis of intralymphatic RDD. Intralymphatic RDD may present as vulvar lymphedema and can potentially mimic other myxedematous neoplasms of the vulvovaginal region.

  View details for DOI 10.1097/PGP.0000000000000619

  View details for PubMedID 31274698

• Molecular Profiling of Intraductal Tubulopapillary Neoplasm Saleem, A., Stehr, H., Zehnder, J., Kunder, C., Lin, C. NATURE PUBLISHING GROUP. 2019

  View details for Web of Science ID 000478915501405

• Concordance Between Immunohistochemistry and Next Generation Sequencing in Testing Patients for Hereditary Nonpolyposis Colorectal Cancer Lawrence, L., Longacre, T., Saleem, A., Kunder, C. NATURE PUBLISHING GROUP. 2019

  View details for Web of Science ID 000478915503448

• Molecular profiling of clear cell adenocarcinoma of the urinary tract. Virchows Archiv : an international journal of pathology Lin, C. Y., Saleem, A., Stehr, H., Zehnder, J. L., Pinsky, B. A., Kunder, C. A. 2019

  Abstract

  Clear cell adenocarcinoma (CCA) of the urinary tract is a rare type of malignancy whose molecular profiles remain undefined. Here we reported an integrated clinicopathologic and molecular profiling analysis of four cases of clear cell adenocarcinoma arising in the urethra or the bladder. Utilizing a clinically validated 130-gene exon-sequencing assay, we identified recurrent pathogenic PIK3CA (p. E545K) and KRAS (p.G12D) variants in three of four (75%) of the cases. In addition, an APC variant (P.S2310X), a TP53 variant (p.R273C), and a MYC amplification event were identified. The only CCA case without either PIK3CA or KRAS variants has a distinct pathogenesis through BK virus, demonstrated by positive BK virus PCR and SV40 immunohistochemistry. The novel finding of recurrent variants in the PI3K/AKT/mTOR pathway provides not only insights into oncogenesis but also potential clinical therapeutic targets for patients with clear cell adenocarcinoma of the urinary tract.

  View details for DOI 10.1007/s00428-019-02634-5

  View details for PubMedID 31372739

• Knowledge and awareness of cervical cancer in Southwestern Ethiopia is lacking: A descriptive analysis. PloS one Saleem, A., Bekele, A., Fitzpatrick, M. B., Mahmoud, E. A., Lin, A. W., Velasco, H. E., Rashed, M. M. 2019; 14 (11): e0215117

  Abstract

  Cervical cancer remains the second most common cancer and cancer-related death among women in Ethiopia. This is the first study, to our knowledge, describing the demographic, and clinicopathologic characteristics of cervical cancer cases in a mainly rural, Southwestern Ethiopian population with a low literacy rate to provide data on the cervical cancer burden and help guide future prevention and intervention efforts.A descriptive analysis of 154 cervical cancer cases at the Jimma University Teaching Hospital in Southwestern Ethiopia from January 2008 -December 2010 was performed. Demographic and clinical characteristics were obtained from patient questionnaires and cervical punch biopsies were histologically examined.Of the 154 participants with a histopathologic diagnosis of cervical cancer, 95.36% had not heard of cervical cancer and 89.6% were locally advanced at the time of diagnosis. Moreover, 86.4% of participants were illiterate, and 62% lived in a rural area.A majority of the 154 women with cervical cancer studied at the Jimma University Teaching Hospital in Southwestern Ethiopia were illiterate, had not heard of cervical cancer and had advanced disease at the time of diagnosis. Given the low rates of literacy and knowledge regarding cervical cancer in this population which has been shown to correlate with a decreased odds of undergoing screening, future interventions to address the cervical cancer burden here must include an effective educational component.

  View details for DOI 10.1371/journal.pone.0215117

  View details for PubMedID 31714915

• A Case Report of Pediatric Clear Cell Carcinoma of the Urinary Bladder Associated With Polyomavirus AJSP-REVIEWS AND REPORTS Saleem, A., Brown, R. A., Higgins, J. T., Troxell, M. L., Kunder, C. A., Pinsky, B. A., Zambrano, E., Kao, C. 2018; 23 (6): 291?95

  View details for DOI 10.1097/PCR.0000000000000284

  View details for Web of Science ID 000457629000012

• Asystolic Arrest From Polypharmacy in a Patient with Status Epilepticus Blackney, K., Rizvi, A., Saleem, A., Hennessey, E. LIPPINCOTT WILLIAMS & WILKINS. 2017: 631

  View details for Web of Science ID 000412683000330