A Path Chosen Long Ago and Where It Went

The same question that was posed to me over 60 years ago and remains relevant for young pathologists today: “Is there a place for a surgical pathologist or the subspecies of a subspecialty anatomic pathologist in academic medicine?”

When I thought that I had an answer to that question many years ago, I was fortunate to have had as a mentor one of the foremost advocates that surgical pathology was indeed something more than simply signing out one case after another, but the case material for the systematic analysis of morphologic detail with clinical outcome to correlate those pathologic findings with prognostic significance. It was on the basis of these clinicopathologic studies that the foundation was established for the formulation of the AJCC Cancer Staging Manual and the College of American Pathologists synoptic reports.^1,2

During the past 60 years, several important techniques and methods emerged from the bench to the bedside. Once the basic ultrastructure of the cell was established,³ its application to the diagnosis of “undifferentiated tumors” through the identification of characteristic substructures such as intercellular junctions, identification of cell specific organelles such as neurosecretory granules and cytoplasmic filaments. The limitations of standard histologic “special stains” in terms of their specificity and sensitivity were no longer a barrier to the ability to differentiate a poorly differentiated carcinoma from a melanoma or Ewing sarcoma from rhabdomyosarcoma, identification of viruses and immune complex diseases of the kidney.^4–7 It was the antigen-antibody reaction and a secondary antibody to horseradish peroxidase that served as the next advance in diagnostic pathology through immunohistochemistry which emerged in the later 1970s and early 1980s with polyclonal and later monoclonal antibodies.^8–10 Like electron microscopy before it, immunohistochemistry expanded beyond a few specialized centers into the general practice of pathology in the community.

We have now moved beyond the identification of nuclear, cytoplasmic, and membranous epitopes to reveal the phenotype of a neoplasm through molecular genetics with the identification of non-random fusion transcripts, loss of heterozygosity, methylation profiles and actionable mutations.^11,12 These molecular aberrations are now the targets for an ever-expanding menu of pathway inhibitors.¹³ What has been summarized highlights the major advances in diagnostic pathology over the past almost 60 years.

Where and How It Began

But how did I come to the decision to pursue pathology, in particular anatomic pathology, with its disease-associated gross and microscopic manifestations at autopsy and surgical specimens? My first encounter with a pathologist occurred in the course of working at St. Mary’s Hospital in the laboratory in my hometown of East St. Louis, Illinois, while an undergraduate at Washington University in St. Louis (WUSTL). I saw firsthand what Joe Campos, MD, did and with him saw my first autopsy. That small flicker became a larger, brighter flame during the second year pathology course at WUSTL School of Medicine with my introduction into the basic pathologic processes and specific diseases across the spectrum of organ systems, age groups and genders. The soon to follow clinical rotations fortified my decision about pathology since it would provide me with the opportunity to encounter these many diseases without the circumscription of a clinical specialty. In the current subspecialty world of anatomic-surgical pathology, I have tried to remain true to the role of general surgical pathologist.

Vietnam in 1967 – 1968

It was between the completion of my PGY-1 year in pathology at Barnes Hospital in St. Louis and the Armed Forces Institute of Pathology (AFIP) that I served the hybrid role of general medical and laboratory officer at the Station Hospital, U.S. Naval Support Activity (NSA), Da Nang, Republic of Vietnam (RVN).¹⁴ Shortly before I left to report to the Field Medical Service School at Camp Pendleton, California, on July 3, 1967, Lauren V. Ackerman, MD, Director of Surgical Pathology, Barnes Hospital-WU Medical Center called me into his office to wish me well. Although I had only completed my first year, he asked me to return to St. Louis upon completion of my tour as one of his five surgical pathology fellows beginning in July, 1970. At least one individual in the world was more hopeful than myself that I would return from RVN. I was leaving behind a pregnant wife with a daughter on the way in October, 1967 and three sons, six-, five-, and four-years old.

Dr. Dehner.

I joined the US Navy’s Ensign 1915 program so that I could support my family while in medical school.¹⁵ One of the conditions of the contract was active duty after my PGY-1 year. It was difficult to know what the Navy expected of me having completed all of one year of pathology residency. The Senior Medical Officer, Harry Paul Mahin, CAPT, MC, USN, to whom I reported in RVN asked me: “Dehner, what am I going to do with you?” After this dubious “welcome aboard,” my next stop was the administrative officer, Daniel A. Brandan, LCDR, MSC, USN, who informed me that my duties were those of an ad hoc general medical officer (GMO) with scheduled assignments to Receiving One (“the pit”) where Marine casualties arrived directly from the field.¹⁶ My primary duty was that of “laboratory officer” whereupon I was introduced to the senior enlisted, Chief Petty Officer (E-8) Leslie. The laboratory was part of a labyrinth of Quonset huts, on an expansive sandy beach extending to the South China Sea. I was the first medical officer to be assigned to the laboratory. It happened that an earlier inspection in 1966 of military hospital laboratories in RVN by Joe M. Blumberg, BG, MC, USA, the senior pathologist in the American military, critiqued the Navy’s Bureau of Medicine and Surgery (BuMed) about the absence of a pathologist at the largest medical facility in RVN.¹⁷ After all, each of the two hospital ships, the USS Sanctuary and USS Repose, each had a board certified pathologist and together the ships had fewer beds than the Station Hospital. I suppose that it could be argued that the Navy still did not have a pathologist at the Station Hospital.

The hospital was located on the Tien Sha peninsula and was separated from the city of Da Nang by the Da Nang River which had been used as a Viet Cong (VC) assault route into the city. Immediately across the road from the hospital was Marine Air Group-16 (MAG-16) on the South China Sea side of the peninsula. MAG-16 was the largest base for the Huey gunships (Bell UH-1) and other aerial assets in the I Corps (five northern provinces to the DMZ). Needless to say MAG-16 was target-rich for rocket and mortar attacks and the hospital was a not infrequent recipient of putative short rounds; those occasions brought us to our bunkers in the middle of the night after a combination of sirens and explosions.

Through the efforts of an excellent crew of 20–25 Navy corpsmen-laboratory technicians, we expanded the clinical laboratory including the blood bank and set up surgical and autopsy pathology with histology. Prior to my arrival, it was necessary to send requested autopsies to one of the hospital ships or Saigon. Once we were set up, hospital deaths, killed in action with no obvious cause of death from an external inspection at graves registration, and a lesser number of forensic cases were the general categories of autopsies. Among the hospital deaths which accounted for ~50% of our autopsies, we had the opportunity to see some of the first cases of so-called Da Nang lung or as it is known today, adult respiratory distress syndrome, with its hyaline membranes, all too familiar to me from those first year autopsies on premature infants. Other notable autopsy cases during that year included cerebral malaria, Japanese B encephalitis, melioidosis, and rabies.^18,19 One case that was particularly challenging was a young Marine who had multiple admissions to the San Diego Navy Hospital for bouts of recurrent lower lobe pneumonia. He made his appearance at the 1^st Medical Battalion on Hill 327 with mid-upper abdominal pain, which was thought to be due to an ulcer, but none was found at surgery and unfortunately he became an intraoperative death. At autopsy a right atrial myxoma was found which had been embolizing to his lungs to account for the past episodes of “pneumonia” and had an intraoperative pulmonary embolus. We had no echocardiogram, CT, or MRI 56 years ago.

Surgical specimens were largely discarded before my arrival. Traumatic injury to the lung, gastrointestinal tract, liver, spleen, kidney, and amputations accounted for the hundreds of specimens. There had been an unfulfilled need to document these resections for the medical record. Additionally, we received specimens from the civilian hospitals which were interesting and challenging.

Every war that the United States has fought in since the First World War has seen advances in the care and survival of casualties and the Vietnam War was no exception.²⁰ The surgical research team under Larry Carey, LCDR, MC, USNR, studied and later reported on aggressive resuscitation, if possible before, and certainly upon arrival from the field via helicopter. These and other studies in the midst of the war demonstrated that rapid volume expansion with Ringer’s lactate in the presence of severe life-threatening trauma significantly improved survival.^21,22 Despite these efforts and excellent care, some of these young Marines ended up on the stainless steel table.

The nautical phrase, all hands on deck, became more than a metaphor during malarial season when we were inundated with dozens upon dozens of thick and thin smears for the detection of Plasmodium vivax or falciparum or both in rare cases. Despite the weekly mefloquine, not every Marine took the big white tablet.

All hands on deck acquired a more comprehensive and immediate response beyond the laboratory with the Tet holiday (Lunar New Year) when a massive, coordinated country-wide offensive by the North Vietnamese army and VC began on the night of 29–30 January 1968; the tactical situation in the Da Nang area was characterized as precarious.²³ As facilities to the north of us in the I Corps were forced to evacuate their casualties, we quickly became the medical facility of last resort for a steady stream of wounded from the field and transfers from the medical battalions. Our own perimeter was not secure, as it became necessary for the Huey gunships from MAG-16 to take their runs from the South China Sea over the hospital to diminish the threat of being overrun from the river by the VC. As part of the Tet offensive, Hue, the old imperial capitol to the north, became the site of protracted urban warfare with 147 killed and 857 wounded Marines representing almost 50% total force casualties.²³ The latter cases arrived on our landing pad or the hospital ships during this campaign.

During my tour (July 1967 to July 1968), we received more than 30,000 admissions, both surgical and medical from the field, and the hospital had expanded to 700 beds, including facilities for POWs. It was an honor to serve with this most dedicated group of physicians, nurses, and corpsmen.²⁴ We were there for the Marines, sailors, allied military forces, Vietnamese civilians, American contract workers, and those who even tried to take our lives. All received equal care as patients.

The Tet offensive was one of a succession of events which had cast shadows over the world as we referred to the continental United States (CONUS): the riots and incineration of major cities to protest the war and civil rights, the assassination of Martin Luther King, Jr, Lyndon Johnson announcing that he would not run for another presidential term, and the killing of Robert F. Kennedy as he campaigned for the presidency. What were we returning home to? I received an answer to that question upon my arrival to CONUS after one year of my life which was summarily judged as a waste by a young man who confronted me in the San Francisco International Airport on my way home to St. Louis to join my family so that we could report to my next duty station.

Armed Forces Institute of Pathology

My two-year tour at the Armed Forces Institute of Pathology (AFIP) was an important next step on the pathway. But before I could take that next step, I was fortunate that Bruce H. Smith, CAPT, MC, USN, was Director of the AFIP. Captain Smith was willing to accept me despite a succession of rebuffs for an assignment to the AFIP by the same BuMed that sent me to Da Nang as a pathologist of sorts. They were unwilling to send me, a mere GMO, to one of the sought after billets at the AFIP which were reserved for real pathologists. I served as Captain Smith’s research assistant and during those two years I had the opportunity to conduct several studies with him and other senior pathologists including Kamal Ishak, MD, PhD, Herbert Taylor, MD, Jason Norris, MD, and Franz Enzinger, MD. One of the studies with Captain Smith was awarded the Wellcome Medal and Prize in 1969 for our paper on fatal motorcycle injuries in military personnel;²⁵ this study among others was cited to support helmet laws for motorcyclists. During this same period, one of my first papers on pyogenic hepatic abscesses in children was published with my beloved mentor and friend, the late John M. Kissane, MD, one of the preeminent pediatric pathologists.²⁶ I discovered the reprint of that paper in the Smith (Bruce H.) Collection with my inscription to Captain Smith in July, 1969, “For the benefit of your knowledge and rich experience in pathology, the freedom of your laboratory and direction to pursue those areas of interest to me. To you, a profound debt of gratitude for accepting me at the Armed Forces Institute of Pathology.”²⁷ As I learned then and have continued to learn throughout this journey of life, a word and a hand of encouragement at moments of doubt and discouragement continue to remind me of the many opportunities afforded to me.

Finishing the Training and Pursuing the Path

Another of those opportunities was the fellowship in surgical pathology that Dr. Ackerman had offered me before I left for RVN. It was an intense year (1970–1971) with the four other fellows (Bruce L. Webber, MB, BS, David Judge, MD, J. Bradley Arthaud, MD, and Kavous Khodadust, MD); we were responsible for frozen sections, gross examinations (no pathology assistants in those days), case sign-out, conferences and completion of a research project. During the fellowship year, I was offered my first faculty position by Dr. Ackerman as an Instructor in Surgical Pathology for the coming academic year, 1971–72. At that time, we had the benefit of 50% off-service time to start and complete projects for presentation and publication and preparation of lectures and laboratory sessions for medical students.

As I had made the decision to pursue an academic career, it was important to have a vision and plan if it was to have any hope for success (whatever that was to be). The plans began with the materials which were the surgical pediatric cases as they came into the gross room. Gross specimens with interesting and characteristic features were taken to Medical Illustration; in those days, both gross and photomicrographs were captured in black and white images, by the master medical photographer Cramer Lewis. Once the invoices began arriving, I was summoned to Dr. Ackerman’s office to render an accounting of my activities and for what purpose. I discussed with him my plan to write a book on pediatric surgical pathology with a format similar to his Surgical Pathology and a companion in a sense to Kissane and Smith’s Pathology of Infancy and Childhood.^28,29 I asked him to approach his publisher with my proposal which he did and in 1975, the first edition of Pediatric Surgical Pathology appeared.³⁰

It had become apparent to me during the fellowship year that pediatric surgical pathology was a tabula rasa as we were called upon by Jessie Ternberg, MD, PhD, and her colleague, Richard Bower, MD, to examine pediatric specimens in the operating room or to perform a frozen section to confirm the diagnosis of Wilms tumor as one example so that dactinomycin could be started in the operating room. Ternberg became the first Director of the Division of Pediatric Surgery in 1972. The director of the Division of Pediatric Hematology-Oncology, Teresa Vietti, MD, was already regarded as the “mother of multimodality cancer treatment” in children; she had co-authored Clinical Pediatric Oncology, the first major reference in pediatric oncology and first chair of the Pediatric Oncology Group.³¹ The third pediatric specialist was William H. McAlister, MD, the first director of pediatric radiology. Was there possibly a niche for pediatric surgical pathology?

During this same period, I organized a short course entitled: Surgical Pathology of Infants and Children, which was offered at the annual meeting of the United States-Canadian Academy of Pathology. There were also presentations at the meeting of the Pediatric Pathology Club, later the Society for Pediatric Pathology. Dr. Ackerman’s unqualified support in the years between 1971 and 1973 set me on a firm, purposeful path.

Minnesota and “Golden Gopher” Years

The transition occurred for many of us in surgical pathology at Barnes and St. Louis Children’s Hospitals in 1973 when Dr. Ackerman retired and moved to the State University of New York, Stonybrook. One of my colleagues, Juan Rosai, MD, who was now a co-author of Ackerman’s Surgical Pathology,²⁸ was ready to take the next step in his career when he accepted the position of Director of Anatomic Pathology at the University of Minnesota Medical School, Twin Cities. He asked me to join him and we were together from 1974 to 1985. We often referred to those years together as our golden years. The move to Minnesota gave me the opportunity to begin our studies on a newly recognized childhood pulmonary neoplasm, pleuropulmonary blastoma (PPB), together with my colleague and friend, John R. Priest, MD, pediatric oncologist. A Registry (International PPB/DICER1 and Ovarian and Testicular Sex Cord Stromal Tumor Registries) to study these tumors was established in 1990. All cases entered into the Registry allowed us to define the natural history and pathology as our understanding of this tumor evolved from a purely cystic lesion thought to represent a benign congenital lung cyst to a high grade primitive, multipatterned sarcoma.³² An important observation to emerge from these studies was the occurrence of PPB and other childhood tumors within families. As these families were identified and willing to participate in molecular genetic studies, a former resident, fellow and now colleague, D. Ashley Hill, MD, identified the germline heterozygous variant in DICER1. The PPB tumor predisposition syndrome (OMIM 601200, 606241) was defined during the Minnesota years.^32,33

While in Minnesota, my friend J. Thomas Stocker, MD, well-known pediatric pathologist, suggested a book project on pediatric pathology but in broader terms beyond pediatric surgical pathology; the fruits of that endeavor, Pediatric Pathology appeared in 1992 and the fifth edition, Stocker and Dehner’s Pediatric Pathology was published in 2021.³⁴ We are currently gearing up for the sixth edition.

Return to Washington University in St. Louis

The return home to St. Louis took place in 1989 when Emil R. Unanue, MD, Chair of the Department of Pathology and Immunology, offered me the position of Director of Anatomic Pathology at the WU Medical Center which I regarded as an honor since it was the same position that Dr. Ackerman held from 1948 to 1973. However, there were many challenges and expectations upon my arrival, but Emil stood by my side and gave me the opportunity (that word again) to rebuild the division with his unconditional support. There was invaluable assistance of my colleagues, Mark R. Wick, MD, Paul Swanson, MD, Deborah Gersell, MD, Michael Kyriakos, MD, Mary Zutter, MD, Cheryl Coffin, MD, Peter Humphrey, MD, PhD, and Frances White MD; the goal of a successful division with their support and loyalty was largely accomplished during the 17 years in that position.

Ta-Chiang Liu, MD, PhD, Associate Professor in Pathology and Immunology at Washington University, and Dr. Dehner.

Photo courtesy of Washington University Record.

Finding a mentor is a complex endeavor, but it should be an individual that you wish to emulate. I was fortunate to have several mentors along the way. When I began my academic career, time was made available to me to think about and create projects and bring them to fruition. If one is only signing out one case after another while trying to establish a career path, the energy can be siphoned off so that creativity loses its vigor. A plan, purpose, persistence and a goal are words that only attain meaning in action and the time to overcome the initial inertia.

Post Facto

As for some final thoughts and reflections on this traveled path: I served in one of the most unpopular wars in US history during which the social and political fabric of my country began to unravel and it continues to reverberate even to this day. I am a proud graduate of WU where I received my undergraduate and medical education, my post-graduate education in pathology, my first faculty appointment, and ultimate current faculty position as professor. This institution has been the home for much of my professional life where the foundation was laid on which any aspirations and any accomplishments were nurtured and facilitated by the likes of Hamburger, Levi-Montalcini, and Moog in my undergraduate years and Trotter, Ackerman, Kissane, Moore, Moyer, Vietti, and Ternberg in my medical school years.³⁵ Each of these individuals instilled in me some part of themselves allowing me to become the person that I am today; the aspiration was to be like them in some manner.

Whether one likes it or not, especially for those of us who have been blessed with a long life, change is inevitable over the course of the journey along the path. We all experience change from our individual perspective in terms of our reaction and how it affects us. With the exception of a few institutions, medical education as it existed in the late 19^th and early 20th century in this country consisted of numerous store-front proprietary schools operated by private practitioners who awarded certificates after a few months. The successor four-year medical schools were university-based with laboratories that supplemented lectures where the latest developments in anatomy, biochemistry, physiology, bacteriology, and pathology provided the basis for understanding disease processes. The revolution in American medical education and its template was initiated by the report of Abraham Flexner who judged the quality of medical schools in the United States and Canada including Washington University’s “medical department;”³⁶ after a two-day evaluation, he concluded that “the school is little better than worst I had seen elsewhere, but absolutely inadequate in every essential respect.”³⁷

One aspect of the current curriculum is the loss of the general and organ system pathology course as an entre into the human disease process. Pathology today is at its best a vignette and this would appear to be the case for many of the other basic sciences that served as the foundation of medicine as a science. It has now become a rush to the bedside to follow clinicians as an apprentice with a truncated period of preparations.

Something has been lost in medical education in my opinion with its shift from a meritocracy to a holistic admission process, the elimination of academic standards of performance, abandonment of board scores, and election to Alpha Omega Alpha as an acknowledgement of academic excellence. Medical education and the practice of medicine have become incorporated into the current social-political ideology with its agenda. Aaron Rothstein, MD, a neurologist, and others have opined that “doctors as doctors are not responsible for poverty, gun violence, racism, climate change, or social injustice;” he further pointed out that in the examination room the physician’s only allegiance is to that patient and his/her health.³⁸ The realist may say to me, “It is no longer your worry Dehner, so enjoy your twilight years.” But it is my concern and my deep respect for this noble profession which still remains for me a “calling.”