Juan Rosai, ‘Master of the Neoplastic Universe’
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Juan Rosai, ‘master of the neoplastic universe’ Michael C. Dugan, MD September 2020—Great mentors, once passed, live on in the ideas, memories, and dreams of their students. For those like me, lucky enough to have been a student of Juan Rosai, MD, and to have heard him speak, the experience will never be forgotten. Thus it is that when I learned of his death in July, at age 79, I could recall descriptions and notations, questions and curiosities, inquisitive and piercing words spoken in a distinctive Italian-Argentinian voice that would usher us—me and a handful of other residents at Yale New Haven Hospital from 1988 to 1991, and others before and after—into the world of surgical pathology. Dr. Rosai was a giant in pathology, a director of anatomic pathology at Yale, a chair of pathology at Memorial Sloan Kettering, and both preceded by his time at the University of Minnesota. He studied surgical pathology under Lauren Ackerman, MD, during the final year of Dr. Ackerman’s tenure at Washington University in St. Louis. It was Dr. Rosai who carried Ackerman’s Surgical Pathology forward from the fifth to its 10th edition. His ninth and 10th editions were published as Rosai and Ackerman’s Surgical Pathology. But much of the fifth and nearly all of the sixth, seventh, and eighth editions, without his name in the title, were written largely by Dr. Rosai. The 10th edition, published in 2011, filled more than 2,600 pages of text. His scope of topics was not limited by the common clinical subspecialties—GI, GU, breast, lung, and others. No, Dr. Rosai felt compelled to know the details of every tissue, organ, and cell, no matter its origin or eventual fate of a tumor destination. Dr. Rosai, with his fellows and residents, was a prolific author of papers that described many entities of many organs for the first time (for example, sinus histiocytosis with massive lymphadenopathy, insular carcinoma of thyroid, follicular variant of papillary carcinoma of thyroid, mixed acinar-neuroendocrine carcinomas of pancreas). Dr. Rosai grew under the tutelage of Dr. Ackerman to become the world’s greatest taxonomist and clinical anatomic detective of neoplasia, a true surgical pathologist. He was brilliant and engaging in his knowledge of tumors of bone, soft tissue, skin, lymph node, and pancreas and their myriad clinical presentations and prognoses, and he was famed for his work defining criteria of thyroid neoplasia and characterizing other endocrine neoplasms. But to those who studied with him he was perhaps better known for his weekly gross and microscopic resident conferences, question-and-answer sessions that would delve into morphologic mimics, the embryologic manifestations of tumors, divergent and mixed differentiation—mesenchymal, endothelial, epithelial, acinar, oncocytic, anaplastic, neuroendocrine, and so on—and the clinical and radiologic features related to their pathologic morphology. Yale Department of Pathology in June 1989. Second row, center: Dr. Rosai. Top row, second from left: Dr. Dugan. Dr. Rosai joined Yale in 1985 as director of anatomic pathology. Dr. Rosai did not simply provide didactic lectures. Rather, he forced us to study the ecology and evolution of the human form descended from the morphology of misshapen anatomy, tumors huge and small, fatty and fibrous, calcified and necrotic, invasive or encapsulated. These masses, delivered or obtained by residents fresh from the operating room, were cut and dissected like archeological digs, examined and photographed for all to see. For us it was a colorful world of splendor and complexity. The best of the best could be quickly humbled in the presence of Dr. Rosai, master of the neoplastic universe. At Yale in early 1991, in the closing months of three years of training with him, I had asked him about or remarked on the various papers starting to mention p53. He said something like, “I don’t really know much about it, but it seems this molecular trend could take over pathology like immunohistochemistry.” “Yes, it seems likely,” I said. Within 20 years of that conversation, molecular diagnostic tests were being used to classify tumors, stratify prognosis, and make targeted treatment decisions. Dr. Rosai compiled and published with several contributors the 1997 book Guiding the Surgeon’s Hand, which describes the history of surgical pathology as traced through many notable pathologists at several American institutions. In the book is a photo of Dr. Rosai and other fellows with Dr. Ackerman at Washington University Barnes Hospital in 1973. It was Dr. Ackerman’s last year of two and a half decades as director of surgical pathology, a period described in the book as one in which surgical pathology evolved dramatically under Dr. Ackerman’s leadership, from an adjunct to surgery and a stepchild of anatomic (autopsy) pathology into a clearly demarcated clinical specialty. In the later 20th century it was Dr. Rosai, as much as anyone, who took this new clinical specialty to its most ambitious heights. Although he loved New York City and the American pathology training programs he had cultivated, Dr. Rosai, born and raised in Argentina to Italian parents, later returned to Milan, Italy, to become director of the Istituto Nazionale dei Tumori (National Cancer Institute) and later continued his consultations at the Centro Diagnostico Italiano in Milan. In 2009, during the USCAP annual meeting, Genzyme Genetics honored Dr. Rosai to commemorate his career by hosting a dinner event. (Dr. Rosai helped develop Impath in New York City, which Genzyme Corp. acquired in 2003 to build its Genzyme Genetics business unit.) There Dr. Rosai reviewed notable papers written by five of his residents or fellows, each of which defined new entities described and characterized over his career.1-5 The historical recap, including Dr. Rosai’s tribute to the significant contributions of William Gerald, MD, a Rosai fellow and faculty member at MSK who died prematurely of cancer in 2008, was a tour de force. It was a quintessential display of Dr. Rosai’s depth, reach, and influence across the field of surgical pathology, which shaped modern cancer classification, staging, treatment, and medical care for many related entities (such as proliferative breast disease and autoimmune disorders of thyroid) in general. Once he had returned to Italy, most of us in the U.S. would get to see Dr. Rosai only at the USCAP meetings, which he attended with his wife and professional colleague, Maria Luisa Carcangiu, MD, until recent years when he was unable to travel. In 2012, when I visited Milan on business, I had the pleasure of joining Dr. Rosai and his wife for dinner. For the first time he mentioned his declining health and said it was becoming more difficult to attend the USCAP annual meeting each year. I thought then: What a shame. What would pathology be without Juan Rosai? It was a moment of apprehension, recognition of our mortality, a fear he might one day be gone. 1. Carcangiu ML, Zampi G, Rosai J. Poorly differentiated (“insular”) thyroid carcinoma. A reinterpretation of Langhans’ “wuchernde Struma.” Am J Surg Pathol. 1984;8(9):655–668. 2. Klimstra DS, Rosai J, Heffess CS. Mixed acinar-endocrine carcinomas of the pancreas. Am J Surg Pathol. 1994;18(8):765–778. 3. Chan JK, Carcangiu ML, Rosai J. Papillary carcinoma of thyroid with exuberant nodular fasciitis-like stroma. Report of three cases. Am J Clin Pathol. 1991;95(3):309–314. 4. Argani P, Erlandson RA, Rosai J. Thymic neuroblastoma in adults: report of three cases with special emphasis on its association with the syndrome of inappropriate secretion of antidiuretic hormone. Am J Clin Pathol. 1997;108(5):537–543. 5. Gerald WL, Rosai J. Case 2. Desmoplastic small cell tumor with divergent differentiation. Pediatr Pathol. 1989;9(2):177–183. Dr. Dugan is chief medical officer and CLIA laboratory medical director at Biocept in San Diego. For more of Dr. Dugan’s recollections of learning from Dr. Rosai and Dr. Rosai’s career, visit https://tinyurl.com/Juan-Rosai..