ADVANCES IN MEDICINE DERIVING FROM DEVELOPMENTS IN ANATOMIC PATHOLOGY: The 20th Century

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ADVANCES IN MEDICINE DERIVING FROM DEVELOPMENTS
IN ANATOMIC PATHOLOGY The 20th Century

• Mark R. Wick, M.D.

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DEFINITION OF RESEARCH(Random House Dictionary
Of the English Language, as quoted in Silverberg
SG, DeLellis RA, Frable WJ Principles Practice
of Surgical Pathology Cytopathology, 3rd Ed.,
1997 p. 8)

• Research Diligent systematic inquiry or
  investigation into a subject in order to discover
  or revise facts, theories, applications, etc.

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Research in Anatomic Pathology (Outlined by
Silverberg SG AJCP 1981 75 452)

• 1. Observational Involves observations of the
  experiments of nature (e.g., clinical specimens
  from human diseases)
• 2. Manipulative Use of diagnostic and triage
  skills to facilitate non-morphologic research on
  human diseases, done with non-pathologist
  collaborators in other disciplines
• 3. Non-human Using animal or in vitro models to
  further study clinical diseases, with or without
  collaborators
• 4. Technical/Instructional/Delivery-Related
  Perfecting new diagnostic techniques, training
  methods, or delivery of better clinical service

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Advances Deriving from Unfunded, Observational
Research in Anatomic Pathology in the 20th
CenturyI. Classification of Disease Entities

• -Essentially all specialized carcinoma, sarcoma,
  blastoma, germ cell tumor, and lymphoma
  morphotypes
• -Pseudoneoplastic quasi-neoplastic disorders
  (e.g., nodular fasciitis, myositis ossificans,
  Rosai-Dorfman disease, virus-associated
  hemophagocytosis)
• -Langerhans non-Langerhans histiocytoses
• -Separation of special melanocytic nevus variants
  from malignant melanoma
• -Characterization of specific non-neoplastic
  inflammatory diseases of the lung, gut, liver,
  and other sites
• -Recognition of the AIDS complex
• -Identification of specific infectious diseases
  (e.g., cytomegalovirus, progressive multifocal
  leukocephalopathy, and others)

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Pneumocystis-AIDS Cytomegalovirus-lung
Rosai-Dorfman Disease-S100
Pleuropulmonary Anaplastic large-
Spitz nevus Sarcomatoid Blastom
a cell lymphoma-ALK-1
carcinoma
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NON-NEOPLASTIC DISEASE ENTITIES DESCRIBED BY
ANATOMIC PATHOLOGISTS IN THE 20TH CENTURY
Selected Examples

• Graft versus host disease
• Lymphangioleiomyomatosis
• Multiloculated thymic cyst
• Inflammatory polyps of the GI tract
• Necrotizing sialometaplasia
• The currently-recognized glomerulonephritides
• Radial scar of the breast
• Microglandular mammary adenosis
• Pseudoneoplastic myositides and fasciitides
• Progressive multifocal leukoencephalopathy
• Kikuchis disease

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Graft-versus-host disease Lymphangioleiomyo-
Dense deposit disease C3 Esophagus
matosis
Progressive multifocal leuko-
Mammary radial scar encephalopathy ISH
for JC virus
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Advances Deriving from Unfunded, Observational
Research in Anatomic Pathology in the 20th
CenturyII. Prognostication of Malignant
Diseases

• -Recognition of the concept of staging
  grading in general development of the
  AJCC/UICC (TNM), FIGO, Rye, Masaoka, Broders,
  Gleason, Mountain, and other specific grading
  staging systems
• -Correlation between histologic nuance and
  biologic behavior (e.g., worsened prognosis in
  alveolar rhabdomyosarcoma, anaplastic Wilms
  tumor, subtypes of DCIS of breast etc.)

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Advances Deriving from Unfunded
Technical/Educational/Delivery-Related Research
in Anatomic Pathology in the 20th Century

• -The entire discipline of cytopathology (both
  exfoliative cytology fine needle aspiration)
• -Diagnostic electron microscopy, immunohistology,
  in-situ hybridization, and molecular techniques
• -Telepathology
• -Laboratory informatics as applied to anatomic
  pathology
• -Application of adjunctive techniques to
  morphologic subtypes of various neoplasms, to
  predict behavior (e.g., flow cytometry in breast
  and colorectal carcinomas neuroblastomas blood
  group antigen immunotyping of urothelial
  carcinomas)

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Cytopathology in the 20th Century Notable
Quotes (from Linder J Johnston WJ-- In
Andersons Pathology, 10th Ed., 1996)

• -The Papanicolaou smear has had unparalleled
  success as a screening test. Since the late
  1940s, the incidence mortality for invasive
  carcinoma of the cervix have declined 70-75 in
  the U.S. The widespread use of the Pap smear is
  generally cited as the major factor influencing
  these trends.
• -The success of the Pap smear fostered interest
  in other cytologic procedures, includingrediscov
  ery of the fine needle aspiration biopsy the
  concordance between FNAB and open tissue biopsy
  now reaches or exceeds 95.

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Diagnostic Electron Microscopy A Paradigm for
Translational Research in Anatomic Pathology
(From Erlandson RA Diagnostic Transmission
Electron Microscopy of Tumors, 1994 p. 2)

• Although ultrastructural studies of specific
  neoplasms for diagnostic purposes were performed
  in a small number of pathology departmentsin the
  early 1960sno significant articles specifically
  devoted to diagnostic TEM of tumors were
  published in the English literature until 1968,
  when Juan Rosai and Hector Rodriguezdescribed
  four tumors in which TEM helped to resolve a
  difficult differential diagnosis.

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Transmission Electron Micrograph of
Pleural Mesothelioma
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Research in Anatomic PathologySummary Statement

• Anatomic pathology serves as a model for the
  beneficial contributions that derive from
  observational and clinically-applied technical
  medical research