Dr. Kamal G. Ishak died unexpectedly of a heart attack at his home on April 5, 2004. He had been in apparently good health and was working productively at the very end of his life. He was widely regarded as one of the foremost hepatic pathologists in the world. Although interested in all types of liver disease, he was especially known for his expertise in liver tumors, inherited metabolic diseases, viral hepatitis, and drug-induced liver injury.1

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Illustration 1. Dr. Kamal G. Ishak

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Kamal was born in Atbara, Sudan, in 1928 to Syrian and Turkish parents. He spent most of his childhood and early adulthood in Cairo, Egypt. His father, recognizing with remarkable insight that English would be the dominant world language in the 20th century, sent his three children to primary and secondary school at the English Mission College in Cairo, where they received a first-rate British education. Kamal subsequently attended Cairo University, graduating M.B., Ch.B. in 1951, followed by a rotating internship and a residency in internal medicine. He was awarded a Fulbright Scholarship at the U.S. Naval Medical Research Unit at Cairo, where he studied schistosomiasis and brucellosis and published his first 16 papers.

Dr. Ishak immigrated to the U.S. in 1957, becoming a naturalized citizen in 1965. He trained in pathology, first at Baptist Memorial Hospital in San Antonio, TX, and then at Baylor University Medical Center in Dallas, TX, where he also enrolled in graduate school, earning a Ph.D. in microbiology. He came to the Armed Forces Institute of Pathology (AFIP) in Washington, DC, in 1963 as a staff pathologist and became chief of the Hepatic Pathology Branch in 1965 upon the retirement of the pioneer hepatopathologist, Hans Smetana.2

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Illustration 2. Left to right: Dr. Ishak, Dr. Zimmerman, Dr. Popper at the AFIP Thursday conference in 1983.

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In the 1960's the AFIP had earned the reputation as the place with definitive answers in pathology. The Institute, founded in 1863 as the Army Medical Museum, had collected specimens from around the world during the expansion of U.S. military engagements that began with the Spanish-American War. During World War II, it established a worldwide network of medical laboratories to diagnose the unusual diseases encountered by the troops. Epidemics of hepatitis during and after the war provided material for seminal publications on the pathology of acute, fulminant and cholestatic viral hepatitis by Drs. Balduin Lucke, Tracy Mallory, Smetana, and I.N. Dubin, who served on the staff of the museum, which became the AFIP in 1947.

Kamal's 40-year career at the AFIP was remarkably productive. He quickly took advantage of the wealth of archived material that had been sent to the institute for consultation. His landmark paper on malignant liver tumors in children (Cancer 1967;20:396–422) defined hepatoblastoma as an entity distinct from hepatocellular carcinoma. It was followed by a series of papers on liver tumors that established his reputation among pathologists. His study of the pathology of phenothiazine hepatotoxicity (Arch Pathol 1972;93:283–304), followed by numerous other papers on medical diseases of the liver, many in collaboration with his close friend, Hyman J. Zimmerman, established his reputation among hepatologists. He wrote 70 book chapters and invited reviews, several long enough to be monographs by themselves. One, published as part of the proceedings of a course on pathogenesis on liver diseases, was 150 printed pages with 97 illustrations and 921 references. His two chapters on liver disease in childhood and metabolic errors and liver disease in the 2001 edition of MacSween's Pathology of the Liver (of which he was coeditor) have a combined length of 150 pages with 166 illustrations and 1998 references. He was a major participant in all three editions of the World Health Organization “blue books,” devoted to the classification of liver tumors, and he was the lead author of the authoritative monograph, “Tumors of the Liver and Intrahepatic Bile Ducts,” published in 2001 as part of the AFIP's Atlas of Tumor Pathology. His most permanent legacy, however, may be the histological activity index for evaluating liver biopsies from patients with chronic hepatitis. He was the pathologist who devised the first version (HEPATOLOGY 1981;1:431–435), popularly known as the “Knodell score” after the lead author of the publication, and he was the lead author (J Hepatol 1995;22:696–699), along with the International Liver Pathology Group (the “Gnomes”), of the modification that has become known as the “Ishak score.” Improvement in the histological activity index has been used as the primary endpoint in clinical trials, leading to regulatory approval for the drugs currently used for treatment of chronic hepatitis B and C, and the index continues to be used in natural history studies and in trials of antiviral and antifibrotic drugs in chronic viral hepatitis.

Because of his reputation, pathological material from diseased livers came to the AFIP from all over the world for second or even third and fourth opinions. The “Dear Dr. Ishak” cases not infrequently had already stumped one or more expert consultants, and Kamal was consulted as the final arbiter. He had an encyclopedic knowledge of pathological and clinical aspects of liver disease and a vast experience gained from study of the AFIP's unique collection of rare and common diseases. He also had an intellectual curiosity that promoted a constant, ongoing review of the medical literature. This combination of qualities gave him the ability to make the really difficult diagnoses in hepatopathology, as well as provide material for his many chapters and reviews. He maintained his enthusiasm for liver disease over the decades, and he always delighted in finding something he had not seen before, either discovering something himself or having the opportunity to study a lesion that had been only rarely reported. Furthermore, having the opportunity to study a case often meant documenting it photographically, especially if it was a good example or an unusual lesion. Over the course of his career, he probably took over 100,000 photomicrographs as well as hundreds of transmission and scanning electron micrographs. It was far more than he could ever hope to use, no matter how many lectures he gave or chapters he wrote, and he was very generous in giving photos to anyone who needed examples (e.g., Hy Zimmerman's Hepatotoxicity contains over 150 of Kamal's pictures). However, most of his pictures were taken for the sheer aesthetic pleasure of capturing these beautiful images on film. Over his career he made the transition from 4×5 lantern slides to 35 mm transparencies, to digital media, always striving for the perfect picture.

Also, because of his reputation, Kamal was invited to lecture all over the world, giving him the opportunity to use parts of his immense photomicrograph collection. He always enjoyed sharing his knowledge with others. For 30 years, he gave courses in Liver Pathology at the annual meeting of the United States and Canadian Academy of Pathology (where I, as a young resident, first encountered him), and for 23 years he directed a Hepatopathology course at the AFIP. He codirected the American Association for the Study of Liver Diseases annual postgraduate courses in 1985 and 1998 and served on the faculty of several others. In 1965, he and Hy Zimmerman established a weekly clinical-pathological case-review conference at the AFIP, still held every Thursday afternoon, to bring together internists, pathologists, surgeons, and basic scientists interested in liver disease. The conference's renown spread, so that visitors to Washington with a hepatological interest often arranged their travel plans to include a Thursday afternoon stop at the AFIP.

Kamal's many official honors include the Distinguished Service Award of the AASLD, an Honorary Fellowship of the Royal College of Pathologists, the President's Award of the United States and Canadian Academy of Pathology, and the Presidential Rank Award, Meritorious Executive, Senior Executive Service, awarded by the President of the United States to only a few top civil servants each year.

Among his friends and coworkers, Kamal was known not only as a great pathologist but also as a great cook. He specialized in Middle Eastern cuisine, and he is perhaps the only world expert who regularly prepared lunch for his entire department. He was also an enthusiastic nature photographer, particularly of flowers, and an avid fan of professional tennis. His wife, Betty Boulton, who was also a pathologist, died in 1970, and he continued raising their two daughters, Leila and Magenta, by himself, always maintaining a warm and affectionate relationship with them until the very end of his life.

Kamal Ishak gave four decades of dedicated service to the AFIP and to the study of liver disease. He was an institution within the institute, and the AFIP, as well as the world of liver pathology, will not be the same without him. Scores of pathologists, hepatologists, and gastroenterologists, as well as several surgeons and radiologists, studied with Kamal over the past 40 years for periods that ranged from a few days to several years. He will be missed, but he will be fondly remembered by those with whom he shared his knowledge, his enthusiasm, and his friendship.