The New England Journal of Medicine

Case Records of the Massachusetts

General Hospital
“Continuing to learn from the patient…”
Nancy Lee Harris, M.D.
Austin L. Vickery Professor of Pathology
Massachusetts General Hospital
Harvard Medical School
Editor, Case Records of the MGH
Clinicopathologic Conferences (CPC’s): History

• 1870’s: Harvard Law School

– Case method of teaching introduced by Christopher Langdell
• Walter B. Cannon, HMS
– Found medical school lectures “a dreary and benumbing process”
– Impressed by the enthusiasm of his roommate, a law student, for
assigned cases
– Introduced case based teaching at HMS in the 1890’s
– 1900: Published “Case method of teaching systemic medicine”in
the Boston Medical and Surgical Journal (later New England
Journal of Medicine)
• Richard C. Cabot
– Used cases as examination and teaching exercises at HMS
– 1906: Published a monograph of case studies
 Richard Cabot
Case Teaching in
Medicine
1906

The subtitle of the book

stated his purpose: to teach
“the differential diagnosis,
prognosis, and treatment
of actual cases of disease.”
Cabot was a renowned
diagnostician; advocated
careful patient histories
and followup (not
universally accepted at the
time)
 CPC’s: History
• 1908: Cabot joined staff of MGH
– Realized his colleagues were unaware of potential of autopsy to clarify
diagnoses
– Together with James Homer Wright (Pathology), established
Clinicopathologic Conferences
– Published privately by MGH 1915-1923
• Published in Boston Medical and Surgical Journal (later
New England Journal of Medicine) since 1923
• Popular conference emulated worldwide
• Editors at MGH
– Richard C. Cabot (1923-1935)
– Tracy B. Mallory (1935-1952)
– Benjamin Castleman (1952-1974)
– Robert E. Scully (1974-2001)
– Nancy Lee Harris (2002-present)
– Eric S. Rosenberg (2007-present)
CPC
Allen
Street
MGH
1930
Tracy B. Mallory
Chief of
Pathology Service
Editor of Case
Records
1935-1952
 Editors of Case Records
Benjamin Castleman (1954-1974)
Robert E. Scully (1974-2001)
 Case Records of the MGH
New England Journal of Medicine
 Evolution of the CPC’s during
the 20th Century
• Cabot initially selected the cases and discussed
them himself
• Later done as unknowns
– Selected by pathologist, usually from cases autopsied at MGH
– Cabot discussed without preparation
– Lively participation of medical students, other physicians
• Initial diagnoses mainly based on autopsy
• Later, surgical biopsies became more common
• With subspecialization in medicine, other
speakers were invited, conferences became more
formal
Changes in the Case Records
CPC’s and NEJM - Mutual Benefit
 Problems Facing the CPC’s
in the 21st Century
• Cases became increasingly esoteric
• Difficult to find discussants
– Interesting cases known to most MGH physicians
– Production of a lengthy differential diagnosis daunting
– Fear of “getting it wrong” in the NEJM
• Conferences poorly attended at MGH
– Busy practitioners, competing conferences
– Issues discussed not seen as relevant to practice
• NEJM dissatisfied with CPC’s
– Reader survey: reduced interest, relevance to practice
– Case histories and discussions overly long
– Other types of case-based articles introduced
 Is the CPC an Anachronism?
• At the turn of the last century
– Focused on differential diagnosis, then the main
activity of physicians.
– Introduced the “new” diagnostic techniques of gross
and microscopic anatomic pathology.
• At the turn of this century
– Improved diagnostic techniques mean few cases are
true diagnostic mysteries that can be solved.
– Improved treatments create more options for
management after diagnosis.
– Physicians typically spend more time on management
than on differential diagnosis.
– CPC’s that focus on unusual differential diagnoses
and rare diseases have limited practical value.
 The CPC’s: Should they Continue?
• Many issues need to be explained to
practitioners:
– New diagnostic techniques
– New prognostic and predictive factors
– New treatments
– New dieases
• NEJM wants case-based exercises that benefit
generalists and trainees.
• The patient mix and expertise of MGH and
Harvard physicians can be an important
resource for physicians and trainees.
• The CPC’s must adapt to modern medicine.
 The Updated CPC Mission
• Educate physicians in the diagnosis,
classification, and treatment of disease,
and in how to use new techniques for
diagnosis and management, using
“actual cases of disease”
– The focus: practical - scientific advances
that enhance understanding of disease in a
way that impacts patient care.
– The readers: medical students, practicing
generalists, specialists
– The forum: national and international
Harris NL.N Engl J Med 2003;348(22):2252
 How do we do this?
Expand the format to include cases that illustrate
issues in management

• Case history; brief discussion of differential

diagnosis
• Radiology, Pathology:
– new diagnostic techniques
– new information about genetics or pathophysiology
– pathologic features that predict prognosis or response to
therapy
• Clinical discussant(s):
– review management options and other issues
– make recommendation for management
• Patient’s actual treatment and outcome are
presented.
 Diagnostic Mystery Cases:
expand possibilities
• Include cases that are not zebras:
– Common diagnostic problems that are still often missed
– “A case where you SHOULD make the diagnosis!”
• Invite discussants who know the diagnosis
– Physicians who actually cared for the patient
– Describe their thought processes as the disease unfolded
– Include both generalists and consultants “called in” to discuss
specific aspects of the case
• Discuss both the differential diagnosis and
management of the patient in the same case
– Avoid the rigid “formula” that had taken over the CPC’s
 Increase Clinical Relevance and
Participation
• Clinical Advisory Committees
– Each Department has a person or committee focused on CPC’s
– Decide what issues are important to cover with appropriate cases
– Identify cases and speakers
• Move conferences to department rounds
– Reach a wider audience
– Provide a forum for discussion
– Chief residents involved in finding cases and speakers
• Involve physicians in training
– House officers prepare case history and present at conference
– Medical students on service present differential diagnosis or
management recommendations
Changes in the CPC’s in the new
millennium: Management cases

Karthikeyan, unpubl letter

Changes in the CPC’s in the new
millennium: Authors per case

Karthikeyan et al unpubl letter

 What makes a good case?
Diagnostic problem
• Unusual presentations or complications of common
diseases
• Typical presentations of uncommon diseases that
practitioners should know about
• “New” diseases or categories
• A broad enough differential diagnosis to lead to an
interesting discussion
• Sufficient clues to permit the correct diagnosis to be
made
• A laboratory or other test that confirms the diagnosis
• Novel diagnostic techniques: radiologic, pathologic
 What makes a good case?
Management problem

• Common problem with controversy on

management
• Diseases with new data
– Diagnostic, prognostic, predictive tests
– New therapies
– “New” diseases or categories
• Unusual problems that people should know about
• There should be an answer!
– Sufficient data to permit an evidence-based approach to
management of the patient
– Sufficient followup to determine whether management
was effective
 What makes a good case?
• A hot topic!
– A young adult dying from influenza
– The first MGH WNV case
– Burn victim from Rhode Island nightclub fire
– Tsunami survivor treated by MGH physicians
– A man impaled in a sculling accident
– A man with respiratory failure due to 2009 pandemic
H1N1 influenza virus
– A case of wrong-site surgery
– A young woman with gastrointestinal anthrax
– A case of Listeriosis (during but not related to the U.S.
outbreak)
– A case of rabies in Massachusetts
“A 17 year-old Indonesian girl with hemiparesis
after being swept up in a tsunami”
 A man impaled in a rowing accident: Diagram of the Patient's Injury

Sheridan R et al. N Engl J Med 2007;356:1353-1360

A New Disease: TEMPI syndrome

A man with telangiectasias, erythrocytosis,

elevated erythropoietin levels, monoclonal
gammopathy, perinephric fluid collections, and
intrapulmonary shunting
 Undiagnosed Medical Condition
• EPO = 4615 mIU/ml
– (Normal 4-16)

• 0.79 g/dl IgG kappa M

component

Massive perinephric fluid

collections requiring
intraperitoneal drainage Pathological diagnosis:
Renal lymphangiectasia
• T = Telangiectasias
• E = Erythrocytosis & Elevated
Erythropoietin
• M = Monoclonal Gammopathy
• P = Perinephric Fluid Collections
• I = Intrapulmonary Shunting
Telangiectasias
 Seven Patients (Alive)

Institution M-protein
MGH IgG-kappa
U. Antwerp, Belgium IgG-kappa
USC, California IgG-kappa
NIH IgG-lambda
Mayo Clinic (Rochester) IgG-kappa
St. Louis University IgA-lambda
Paris, France IgA-lambda
Perinephric Fluid
Serum Erythropoietin
TEMPI: Treatment Response
Institution Treatment
MGH PR to bortezomib

U. Antwerp, Belgium CR to bortezomib

USC, California PR to bortezomib

NIH PR to bortezomib
On treatment (Cy-Bor-
Mayo Clinic (Rochester)
Dex)
St. Louis University No insurance

Paris, France Not on treatment

 TEMPI Syndrome

• Response to bortezomib suggest the paraprotein

is causing the signs and symptoms of the
disease.
• Efforts to identify the target of the paraprotein
are ongoing.
 The CPC’s: How do we do it?
• Finding cases:
– Clinical advisory committee members identify topics
and cases
– Pathology residents and faculty suggest cases
– Chief residents in clinical services suggest cases
– Editor reviews preliminary autopsy reports, attends
conferences where cases are discussed
• Organizing the conferences:
– Discussions with Editor and clinical colleagues re
topic, case, discussants, format
– Associate editor prepares case history (protocol)
– Two assistants help organize conferences,
coordinate speakers
 The CPC’s: How do we do it?
• Preparing the manuscript:
– Discussants required to submit manuscripts, images, tables
and references at the time of the conference
– Conferences are taped
– Editorial assistants transcribe proceedings, prepare rough
manuscripts
– Editor edits to NEJM specifications (length, focus, selecting
images)
• Editors responsible for turning in
publishable ms (40/year)
– Electronically submitted via Manuscript Central
– JMD reviews, requests edits (“too much like a review
article! Focus on the patient!”)
– Accepted ms goes to manuscript editing
– Galleys, page proofs generate innumerable questions for all
authors!
– Letters to the editor…
 CPC’s: Issues that Arise
• Do all the patients have to be seen at MGH?
– Yes, but..
• Can patients or families attend the conferences?
– Who decides?
• Do we need patient permission to discuss and
publish the case? (HIPAA)
– What if they say no?
• What about cases that illustrate problems in care
or have a bad outcome?
– Legal issues?
• Authors: financial conflicts of interest?
– Can a discussant have financial ties to a company making a
product used in the case?
 The Case Challenge!

• Every other month, a case history is posted

on the NEJM website 1 week before
publication of the CPC.
• Readers are asked to vote on the correct
diagnosis (multiple choice).
• Results of voting can be seen in real time on
the web.
• Readers use the “comment” section to
discuss their reasoning and choice of
diagnostic test.
• 2 cases so far in 2013: >6000 readers voted!
– Case 4-2013: A man with acute flank pain
– Case 10-2013: A man with fever, arthralgia, and rash
 The CPC’s in the Future
• Case-based teaching will continue to be important in
medicine.
• Cases can focus on either differential diagnosis or
management of disease - or both.
• Experienced physicians can demonstrate the application
of modern medical advances to the care of an individual
patient.
• The CPC’s can have an ongoing impact on the training of
medical students and the practice of medicine around the
world.
• What can we do to make them more interesting for you?