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Andrew H Fischer MD

InstitutionUMass Chan Medical School
AddressUMass Chan Medical School
One Innovation Drive Biotech Three
Worcester MA 01605
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    InstitutionT.H. Chan School of Medicine
    DivisionAnatomic Pathology

    InstitutionT.H. Chan School of Medicine

    Collapse Biography 
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    Cornell University, Ithaca, NY, United StatesBSCell Biology
    Brown University Warren Alpert Medical School, Providence, RI, United StatesMD

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    Academic Background:

    BS (Cell Biology), Cornell University, Ithaca, NY

    MD, Brown University, Providence, Rhode Island

    Resident, Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA

    Cytopathology Fellow with Prabodh Gupta, Hospital of the University of Pennsylvania, Philadelphia, PA

    Academic Interests:

    Cytology is the field that uses the smallest possible biopsy for diagnosis, by identifying structural changes in cells and small tissue fragments. My basic research interest has been to try to define diagnostic structural changes in molecular terms (see Basic Science Research Interest below).

    My clinical interest is fine needle aspiration (FNA) biopsy. FNAs are minimally invasive, safe, rapid, and relatively painless means of definitive diagnosis. Having performed over 2,500 FNAs in my career so far, a UMASS ultrasound-guided STAT FNA Clinic has been started whereby a Cytopathologist performs and immediately interprets the FNA.

    I have also been interested in developing technical solutions to the problem of acquiring and processing microsized pieces of tissue for diagnosis. I invented the CellientTM Automated Cell Block System (covered with eight patents), licensed to Hologic Corporation in Marlborough, MA.  CellientTM automatically recovers small tissue fragments from a specimen container and delivers them to an indexable plane in paraffin for histologic sectioning in under one hour. CellientTM allows fine needle (22-25 guage) biopsies to be examined in essentially the same manner as much larger core biopsies, with essentially 100% recovery and no chance for cross contamination during processing. Two other patents relate to automated processing and embedding of larger biopsies.  An improved microbiopsy needle was patented and clinical trials are pending.  Automating rapid onsite assessment of adequacy of microbiopsies is an important goal for Cytology. 

    As criteria become defined at a molecular level, and techniques for procuring and handling micro-sized biopsies are developed, most cancers can be diagnosed with minimally invasive, rapid, and safe cytologic techniques.

    Basic Science Research Interests:

    In spite of years of progress in cancer research, the diagnosis of cancer still generally requires a pathologist to examine a biopsy by light microscopy. Cytopathologists are experts at recognizing changes in cell structure that are diagnostic of various cancers. Surprisingly, cancer researchers still know very little about how or why cancer cells are structured differently from normal cells.  My long term goal is to bridge the molecular and cellular levels, to learn the biochemical basis and functional significance of diagnostic changes in the structure of cancer cells. My lab has developed the idea that there are predictable relationships between cellular-level structural changes diagnostic of cancer and the genes that are active. In some cases (predictably), cancer genes directly induce the changes diagnostic of the particular cancers associated with the genes.  We have identified 8 different cancer genes with such a relationship to diagnostic cell structural changes, involving chromatin and the nuclear envelope, characteristic of different types of cancers. We think that the structural changes oncogenes induce during their activation provide an essential insight into the functional changes that occur during carcinogenesis.

    Nuclear envelope irregularity and changes in large-scale chromatin organization are important diagnostic alterations in many forms of cancer. We have been focused on a pair of tyrosine kinases—RET/PTC and TRK/PTC—that induce the nuclear envelope irregularity and chromatin dispersal diagnostic of papillary thyroid carcinoma. Very likely, but still unproven, these will function very similar to B-RAF V600E in inducing these cellular level diagnostic structural changes.  We have determined the phosphotyrosine docking site on these tyrosine kinases that mediates these changes. We showed that the nuclear lamina composition is very similar between papillary thyroid carcinomas and normal thyroid, and histone composition at a global level is not apparently altered for H3K4m, H3K9m, H3K9/14Ac, and H3K27m. Using micro-injection of RET/PTC into normal thyroid cells in culture, we showed that nuclear envelope irregularity develops during interphase, without an intervening post-mitotic nuclear envelope reassembly, because the nuclear envelope is distorted actively during interphase by forces exerted on it from the cytoskeleton and/or chromatin. Using cell lines we confirmed that there are active interphase deflections of the nuclear lamina in prostate cancer, and we found that depolymerization of actin or microtubules does not inhibit these dynamics, as if chromatin-based forces distorted the nuclear lamina.

    The finding of dynamic changes led us to develope a technique for immobilizing living human tissue fragments with mussel-adhesive protein, and performing two-photon microscopy in time lapse.  This live tissue imaging system is amenable to gene editing and therefore offers the potential to model human disease dynamics in vitro.

    The paradigm that cancer genes are linked predictably and directly to diagnostic cell structural changes should lead to improved diagnosis of cancer, insight into novel cell physiologies involving chromatin and the nuclear envelope, and a basis for a large-scale screen for novel anticancer drugs. Live cell imaging techniques seem likely to expose new sets of dynamic structural changes with a diagnostic utility surpassing that of classical static imaging.


    Cytopathology Fellowship Available-

    One position is available for an ACGME-accredited one-year Cytopathology Fellowship. The Fellowship is unique in integrating Cell Biology concepts related to Cytopathology and offering basic research opportunities related to understanding the molecular basis of diagnostic morphologic cellular changes in cancer cells. The program also offers extensive training in performance of ultrasound-guided FNA, and the potential to participate in technology development related to biopsy devices and specimen processing. Candidates must be AP or AP/CP eligible, and preference will be given to candidates interested in participating in ongoing research. The full curriculum includes a strong foundation in classical morphologic diagnosis (125,000 GYN, 10,000 non-GYN per year for the combined Quest-UMASS venture), ultrasound-guided FNA performance and interpretation (about 200 per year), integration of Molecular Pathology and flow cytometry, cytopreparatory methods, and laboratory management. Stipend is determined by years of post-graduate experience. Click here for more information.


    Collapse Bibliographic 
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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Bai S, Millis M, Wilson S, Scott M, Goulart RA, Maxfield MW, Lou F, Sood RN, Fischer AH. Liquid-based rapid onsite evaluation of endobronchial ultrasound cytologies. J Am Soc Cytopathol. 2022 Nov-Dec; 11(6):375-384. PMID: 36055932.
      Citations:    Fields:    Translation:Humans
    2. Jermain PR, Fischer AH, Joseph L, Muzikansky A, Yaroslavsky AN. Fluorescence Polarization Imaging of Methylene Blue Facilitates Quantitative Detection of Thyroid Cancer in Single Cells. Cancers (Basel). 2022 Mar 05; 14(5). PMID: 35267647.
    3. Iesato A, Li S, Roti G, Hacker MR, Fischer AH, Nucera C. Lenvatinib Targets PDGFR-? Pericytes and Inhibits Synergy With Thyroid Carcinoma Cells: Novel Translational Insights. J Clin Endocrinol Metab. 2021 11 19; 106(12):3569-3590. PMID: 34302727.
      Citations: 3     Fields:    Translation:HumansCells
    4. Sun T, Hutchinson L, Tomaszewicz K, Caporelli ML, Meng X, McCauley K, Fischer AH, Cosar EF, Cornejo KM. Diagnostic value of a comprehensive, urothelial carcinoma-specific next-generation sequencing panel in urine cytology and bladder tumor specimens. Cancer Cytopathol. 2021 07; 129(7):537-547. PMID: 33539671.
      Citations: 1     Fields:    Translation:Humans
    5. Harris T, Sheel A, Zong Y, Hutchinson LM, Cornejo KM, Bubendorf L, Yates J, Fischer AH. Cytologically targeted next-generation sequencing: a synergy for diagnosing urothelial carcinoma. J Am Soc Cytopathol. 2021 Jan-Feb; 10(1):94-102. PMID: 33184010.
      Citations: 2     Fields:    Translation:Humans
    6. Zou T, Dave S, Adler RN, Manning MJ, Scott MP, Strock C, Kandil D, Cosar E, Fischer AH. Colposcopic endocervical brushing cytology appears to be more sensitive than histologic endocervical curettage for detecting endocervical adenocarcinoma. J Am Soc Cytopathol. 2021 Mar-Apr; 10(2):135-140. PMID: 33097463.
      Citations: 2     Fields:    Translation:Humans
    7. Sun T, Akalin A, Dresser K, Fischer AH, Zuo T. The Utility of MYB Immunohistochemistry (IHC) in Fine Needle Aspiration (FNA) Diagnosis of Adenoid Cystic Carcinoma (AdCC). Head Neck Pathol. 2021 Jun; 15(2):389-394. PMID: 32661670.
      Citations: 3     Fields:    Translation:Humans
    8. Sheridan TB, Walavalkar V, Yates JK, Owens CL, Fischer AH. Cytologic processing of ureteral microbiopsies is associated with higher sensitivity for detection of urothelial carcinoma compared with conventional biopsy processing. J Am Soc Cytopathol. 2020 Jan - Feb; 9(1):26-32. PMID: 31564532.
      Citations: 1     Fields:    Translation:Humans
    9. Fischer AH. New quantitative data on cell blocks. J Am Soc Cytopathol. 2019 Mar - Apr; 8(2):49-51. PMID: 31287419.
      Citations: 1     Fields:    
    10. Schmolze DB, Fischer AH. An Automatable Method for Determining Adequacy of Thyroid Fine-Needle Aspiration Samples. Arch Pathol Lab Med. 2019 09; 143(9):1084-1088. PMID: 30354272.
      Citations: 1     Fields:    Translation:Humans
    11. Lee PJ, Owens CL, Lithgow MY, Jiang Z, Fischer AH. Causes of false-negative for high-grade urothelial carcinoma in urine cytology. Diagn Cytopathol. 2016 Dec; 44(12):994-999. PMID: 27781412.
      Citations: 4     Fields:    Translation:Humans
    12. Fischer AH, Hutchinson LM. Technical and US regulatory issues in triaging material for the molecular laboratory. Cancer Cytopathol. 2017 02; 125(2):83-90. PMID: 27598019.
      Citations: 1     Fields:    Translation:Humans
    13. Duquette M, Sadow PM, Husain A, Sims JN, Antonello ZA, Fischer AH, Song C, Castellanos-Rizaldos E, Makrigiorgos GM, Kurebayashi J, Nose V, Van Hummelen P, Bronson RT, Vinco M, Giordano TJ, Dias-Santagata D, Pandolfi PP, Nucera C. Metastasis-associated MCL1 and P16 copy number alterations dictate resistance to vemurafenib in a BRAFV600E patient-derived papillary thyroid carcinoma preclinical model. Oncotarget. 2015 Dec 15; 6(40):42445-67. PMID: 26636651.
      Citations: 26     Fields:    Translation:HumansAnimals
    14. Walavalkar V, Fischer AH, Owens CL. Significance of cytopathologist's review of Pap tests screened as negative for intraepithelial lesion or malignancy that are positive for high-risk human papillomavirus. J Am Soc Cytopathol. 2015 Jul - Aug; 4(4):190-194. PMID: 31051753.
      Citations:    Fields:    
    15. Walavalkar V, Patwardhan RV, Owens CL, Lithgow M, Wang X, Akalin A, Nompleggi DJ, Zivny J, Wassef W, Marshall C, Levey J, Walter O, Fischer AH. Utility of liquid-based cytologic examination of distal esophageal brushings in the management of Barrett esophagus: a prospective study of 45 cases. J Am Soc Cytopathol. 2015 May - Jun; 4(3):113-121. PMID: 31051691.
      Citations:    Fields:    
    16. Fischer AH, Schwartz MR, Moriarty AT, Wilbur DC, Souers R, Fatheree L, Booth CN, Clayton AC, Kurtyz DF, Padmanabhan V, Crothers BA. Immunohistochemistry practices of cytopathology laboratories: a survey of participants in the College of American Pathologists Nongynecologic Cytopathology Education Program. Arch Pathol Lab Med. 2014 Sep; 138(9):1167-72. PMID: 24840035.
      Citations: 16     Fields:    Translation:Humans
    17. Zhao C, Li Z, Nayar R, Levi AW, Winkler BA, Moriarty AT, Barkan GA, Rao J, Miller F, Fan F, Zhou Z, Si Q, Fischer AH, Sturgis CD, Jing X, Marshall CB, Witt BL, Birdsong GG, Crothers BA. Prior high-risk human papillomavirus testing and Papanicolaou test results of 70 invasive cervical carcinomas diagnosed in 2012: results of a retrospective multicenter study. Arch Pathol Lab Med. 2015 Feb; 139(2):184-8. PMID: 24694342.
      Citations: 9     Fields:    Translation:HumansCells
    18. Walavalkar V, Fischer AH, Owens CL. Cytologic diagnosis of metastatic alveolar rhabdomyosarcoma to the thyroid gland by fine-needle aspiration. Acta Cytol. 2014; 58(3):288-92. PMID: 24513670.
      Citations:    Fields:    Translation:Humans
    19. Fischer AH. The diagnostic pathology of the nuclear envelope in human cancers. Adv Exp Med Biol. 2014; 773:49-75. PMID: 24563343.
      Citations: 9     Fields:    Translation:HumansCells
    20. Larson AR, Lee CW, Lezcano C, Zhan Q, Huang J, Fischer AH, Murphy GF. Melanoma spheroid formation involves laminin-associated vasculogenic mimicry. Am J Pathol. 2014 Jan; 184(1):71-8. PMID: 24332013.
      Citations: 15     Fields:    Translation:HumansAnimalsCells
    21. Lee PJ, Owens CL, Hutchinson L, Fischer AH. Intranuclear cytoplasmic inclusions are a specific feature of intraductal papillary mucinous neoplasms that distinguish contaminating gastric epithelium. J Am Soc Cytopathol. 2014 Mar - Apr; 3(2):108-113. PMID: 31051700.
      Citations:    Fields:    
    22. Walavalkar V, Tommet D, Fischer AH, Liu Y, Papa DM, Owens CL. Evidence for increasing usage of low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion (LSIL-H) Pap test interpretations. Cancer Cytopathol. 2014 Feb; 122(2):123-7. PMID: 23983192.
      Citations: 1     Fields:    Translation:Humans
    23. Fischer AH, Benedict CC, Amrikachi M. Five top stories in cytopathology. Arch Pathol Lab Med. 2013 Jul; 137(7):894-906. PMID: 23808461.
      Citations:    Fields:    Translation:Humans
    24. Moriarty AT, Bentz JS, Winkler B, Fischer AH, Laucirica R, Souers RJ, Thomas N, Zhao C. The College of American Pathologists' first 3 years' experience with high-risk human papillomavirus proficiency testing for cytology and other laboratories. Arch Pathol Lab Med. 2013 May; 137(5):606-9. PMID: 23627450.
      Citations:    Fields:    Translation:Humans
    25. Fischer AH, Clayton AC, Bentz JS, Wasserman PG, Henry MR, Souers RJ, Moriarty AT. Performance differences between conventional smears and liquid-based preparations of thyroid fine-needle aspiration samples: analysis of 47,076 responses in the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytology. Arch Pathol Lab Med. 2013 Jan; 137(1):26-31. PMID: 23276172.
      Citations: 10     Fields:    Translation:Humans
    26. Jean-Gilles J, Fischer AH, Luu MH, Owens CL. Clinical and pathologic features and clinical impact of false negative thyroid fine-needle aspirations. Cancer Cytopathol. 2012 Oct 25; 120(5):326-33. PMID: 22528560.
      Citations: 3     Fields:    Translation:Humans
    27. Luu MH, Fischer AH, Stockl TJ, Pisharodi L, Owens CL. Atypical follicular cells with equivocal features of papillary thyroid carcinoma is not a low-risk cytologic diagnosis. Acta Cytol. 2011; 55(6):526-30. PMID: 22156461.
      Citations: 8     Fields:    Translation:Humans
    28. Paull PE, Hyatt BJ, Wassef W, Fischer AH. Confocal laser endomicroscopy: a primer for pathologists. Arch Pathol Lab Med. 2011 Oct; 135(10):1343-8. PMID: 21970490.
      Citations: 17     Fields:    Translation:HumansAnimals
    29. Fischer AH, Cibas ES, Howell LP, Kurian EM, Laucirica R, Moriarty AT, Renshaw AA, Zakowski MF, Young NA. Role of cytology in the management of non-small-cell lung cancer. J Clin Oncol. 2011 Aug 20; 29(24):3331-2; author reply 3332-3. PMID: 21768461.
      Citations: 8     Fields:    Translation:Humans
    30. Nucera C, Nehs MA, Nagarkatti SS, Sadow PM, Mekel M, Fischer AH, Lin PS, Bollag GE, Lawler J, Hodin RA, Parangi S. Targeting BRAFV600E with PLX4720 displays potent antimigratory and anti-invasive activity in preclinical models of human thyroid cancer. Oncologist. 2011; 16(3):296-309. PMID: 21355020.
      Citations: 44     Fields:    Translation:HumansAnimalsCells
    31. Schmolze DB, Standley C, Fogarty KE, Fischer AH. Advances in microscopy techniques. Arch Pathol Lab Med. 2011 Feb; 135(2):255-63. PMID: 21284447.
      Citations: 13     Fields:    Translation:HumansAnimals
    32. Luu MH, Fischer AH, Pisharodi L, Owens CL. Improved preoperative definitive diagnosis of papillary thyroid carcinoma in FNAs prepared with both ThinPrep and conventional smears compared with FNAs prepared with ThinPrep alone. Cancer Cytopathol. 2011 Feb 25; 119(1):68-73. PMID: 21140483.
      Citations: 11     Fields:    Translation:Humans
    33. Fischer AH, Zhao C, Li QK, Gustafson KS, Eltoum IE, Tambouret R, Benstein B, Savaloja LC, Kulesza P. The cytologic criteria of malignancy. J Cell Biochem. 2010 Jul 01; 110(4):795-811. PMID: 20564180.
      Citations: 19     Fields:    Translation:Humans
    34. Fischer AH. Circulating tumor cells: seeing is believing. Arch Pathol Lab Med. 2009 Sep; 133(9):1367-9. PMID: 19722740.
      Citations: 6     Fields:    Translation:HumansCells
    35. Jaffar R, Mohanty SK, Khan A, Fischer AH. Hemosiderin laden macrophages and hemosiderin within follicular cells distinguish benign follicular lesions from follicular neoplasms. Cytojournal. 2009 Jan 19; 6:3. PMID: 19495407.
    36. Yantiss RK, Cosar E, Fischer AH. Use of IMP3 in identification of carcinoma in fine needle aspiration biopsies of pancreas. Acta Cytol. 2008 Mar-Apr; 52(2):133-8. PMID: 18499984.
      Citations: 11     Fields:    Translation:HumansCells
    37. Li C, Zota V, Woda BA, Rock KL, Fraire AE, Jiang Z, Lu D, Xu B, Dresser K, Lutman CV, Fischer AH. Expression of a novel oncofetal mRNA-binding protein IMP3 in endometrial carcinomas: diagnostic significance and clinicopathologic correlations. Mod Pathol. 2007 Dec; 20(12):1263-8. PMID: 17885673.
      Citations: 19     Fields:    Translation:Humans
    38. Istvanic S, Fischer AH, Banner BF, Eaton DM, Larkin AC, Khan A. Cell blocks of breast FNAs frequently allow diagnosis of invasion or histological classification of proliferative changes. Diagn Cytopathol. 2007 May; 35(5):263-9. PMID: 17427225.
      Citations: 3     Fields:    Translation:Humans
    39. Underwood JM, Imbalzano KM, Weaver VM, Fischer AH, Imbalzano AN, Nickerson JA. The ultrastructure of MCF-10A acini. J Cell Physiol. 2006 Jul; 208(1):141-8. PMID: 16607610.
      Citations: 43     Fields:    Translation:HumansCells
    40. Angeletti C, Harvey NR, Khomitch V, Fischer AH, Levenson RM, Rimm DL. Detection of malignancy in cytology specimens using spectral-spatial analysis. Lab Invest. 2005 Dec; 85(12):1555-64. PMID: 16200074.
      Citations: 10     Fields:    Translation:Humans
    41. Hill DA, Chiosea S, Jamaluddin S, Roy K, Fischer AH, Boyd DD, Nickerson JA, Imbalzano AN. Inducible changes in cell size and attachment area due to expression of a mutant SWI/SNF chromatin remodeling enzyme. J Cell Sci. 2004 Nov 15; 117(Pt 24):5847-54. PMID: 15537831.
      Citations: 17     Fields:    Translation:HumansAnimalsCells
    42. Zink D, Fischer AH, Nickerson JA. Nuclear structure in cancer cells. Nat Rev Cancer. 2004 Sep; 4(9):677-87. PMID: 15343274.
      Citations: 418     Fields:    Translation:HumansCells
    43. Fischer AH, Young KA, DeLellis RA. Incorporating pathologists' criteria of malignancy into the evolutionary model for cancer development. J Cell Biochem. 2004 Sep 01; 93(1):28-36. PMID: 15352159.
      Citations: 6     Fields:    Translation:Humans
    44. Fischer AH, Bardarov S, Jiang Z. Molecular aspects of diagnostic nucleolar and nuclear envelope changes in prostate cancer. J Cell Biochem. 2004 Jan 01; 91(1):170-84. PMID: 14689589.
      Citations: 15     Fields:    Translation:HumansCells
    45. Fischer AH, Taysavang P, Jhiang SM. Nuclear envelope irregularity is induced by RET/PTC during interphase. Am J Pathol. 2003 Sep; 163(3):1091-100. PMID: 12937150.
      Citations: 22     Fields:    Translation:HumansCells
    46. Zhu Z, Gandhi M, Nikiforova MN, Fischer AH, Nikiforov YE. Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations. Am J Clin Pathol. 2003 Jul; 120(1):71-7. PMID: 12866375.
      Citations: 120     Fields:    Translation:Humans
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