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MEN I pancreas: A histological and immunohistochemical study

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Abstract

The spectrum and extent of islet cell histopathological findings in patients with multiple endocrine neoplasia, type I (MEN I) syndrome has never been clearly defined. Although some patients have discreet tumors causing clinically evident syndromes, others may have no symptoms until metastatic islet cell carcinoma is apparent. Whether diffuse islet cell disease occurs in all patients with grossly apparent tumors is not known. This study is an attempt to define both the functional and anatomical extent of islet cell disease and its relationship with the clinical course of patients with MEN I syndrome.

The resected specimens of pancreas from 14 patients with MEN I syndrome were evaluated for hyperplasia, nesidioblastosis, multiple tumors, and evidence of malignancy. In 12 cases, specimens consisted of distal pancreas and, in 2 cases, the entire pancreas was available. Multiple sections were taken from each specimen. Immunoperoxidase staining was done for gastrin, pancreatic polypeptide, glucagon, serotonin, VIP, somatostatin, and neuron-specific enolase in sections of 24 tumors from 10 patients. Five of the 10 patients with Zollinger-Ellison syndrome underwent total gastrectomy and 3 others underwent only pancreatic procedures to control their acid hypersecretion.

The following is concluded. All MEN I patients with pancreatic neoplasms have diffuse islet cell involvement consisting of nesidioblastosis, micro- and macronodular hyperplasia. Some tumors produce multiple hormones and these patients are at risk to develop new tumors, but complete excision of grossly apparent tumors may result in long-term control of the endocrinopathy present. This is particularly true for patients with insulinoma and hypoglycemia. Selected patients with gastrinoma may also be considered for excision of their islet cell tumor(s) without concomitant gastrectomy, especially if transhepatic venous sampling demonstrates a single site of excess gastrin production. However, if transhepatic venous sampling demonstrates diffuse sources of hypergastrinemia, a local pancreatic procedure will invariably be unsuccessful. Total pancreatectomy in MEN I patients with disease localized to the pancreas is the only curative surgical procedure but is rarely indicated.

Résumé

L'histopathologie des cellules insulaires pancréatiques des malades qui présentent un syndrome MEN I n'a jamais été parfaitement définie. Si certains parmi eux sont porteurs de petites tumeurs qui se manifestent par des syndromes cliniques patents, d'autres n'accusent aucun symptôme avant que des métastases néoplasiques ne se manifestent. En particulier, on ne sait pas si les altérations des cellules insulaires sont diffuses quand les malades présentent des tumeurs évidentes. Cette étude a pour but de définir à la fois l'importance anatomique et l'importance fonctionnelle de la maladie insulaire par rapport à son expression clinique chez les sujets concernés par ce syndrome.

Pour ce faire, des spécimens provenant de 14 malades atteints du syndrome MEN I ont été étudiés eu égard à l'hyperplasie, à la nésidioblastose, à la multiplicité des îlots tumoraux, à la malignité.

Dans 12 cas, les spécimens répondaient au pancréas distal, dans 2 cas à la totalité du pancréas. De multiples coupes furent pratiquées au niveau de chaque pièce soumise à l'examen. L'imprégnation à l'immunoperoxidase concerna les coupes de 24 tumeurs provenant de 10 patients. Cinq des 10 malades qui présentaient un syndrome de Zollinger-Ellison avaient subi une gastrectomie totale et 3 une intervention pancréatique pour contrôler leur hypersécrétion acide.

Les conclusions tirées de cette étude furent les suivantes: tous les malades accusant un syndrome MEN I et porteurs d'un néopolasme pancréatique présentaient des lésions insulaires diffuses répondant à une nésidioblastose, à une hyperplasie micronodulaire et macronodulaire. Quelques tumeurs produisaient de multiples hormones: gastrine, polypeptide pancréatique, glucagon, sérotonine, V.I.P., somatostatine, testées par la méthode. Il résulte de ces constatations que les risques de récidive tumorale après exérèse complète des tumeurs évidentes ne sont pas à écarter, encore que l'exérèse permette de contrôler longtemps l'endocrinopathie.

Ceci est particulièrement vrai pour les insulinomes hypoglycémiants. En ce qui concerne les gastrinomes, leur exérèse peut être suffisante, en particulier lorsque les prélèvements veineux étagés montrent qu'ils sont uniques; la gastrectomie concomitante est alors inutile. En revanche, lorsque la gastrine est trouvée en excès au niveau de multiples échantillons veineux, l'exérèse tumorale est insuffisante et la pancréatectomie totale représente l'intervention indispensable; en fait, son indication est rare.

Resumen

La variedad del espectro de la histopatología de las células insulares en pacientes con sindrome de neoplasias endocrinas múltiples tipo I (NEM I) todavía no ha sido claramente definido. Aún cuando algunos pacientes poseen tumores discretos que causan síndromes clínicamente evidentes, otros pueden no exhibir sintomatología alguna hasta cuando se hace evidente un carcinoma metastásico de células insulares. No se sabe si hay enfermedad difusa de las células insulares en todo paciente con tumores macroscópicamente aparentes, ni además se conoce con qué frecuencia se desarrollan nuevos tumores en pacientes con síndrome NEM I después de resección local o de pancreatectomía parcial para tumores primarios de células insulares. El presente estudio intenta definir la extensión funcional y anatómica de la enfermedad de las células insulares y su relación con la evolución clínica en pacientes con el síndrome NEM I.

Los especímenes de resección pancreática en 14 pacientes con síndrome NEM I fueron examinados para hiperplasia, nesidioblastosis, tumores múltiples y evidencia de malignidad. Los especímenes representaron el páncreas distal en 12 casos, y la totalidad del páncreas en 2. Se tomaron secciones multiples de cada espécimen. La coloración con inmunoperoxidasa fue realizada para gastrina, polipéptido pancreático, glucagón, serotonina, VIP (péptido vasoactivo intestinal), somatostatina y enolasa neuronal específica en secciones de 24 tumores provenientes de 10 pacientes. Cinco de los 10 pacientes con el síndrome de Zollinger-Ellison fueron sometidos a gastrectomía total y otros tres sólo a procedimientos sobre el páncreas orientados al control de su hipersecreción ácida.

Se llega a las siguientes conclusiones: Todos los pacientes con síndrome NEM I y neoplasias pancreáticas poseen afección difusa de las células insulares consistente en nesidioblastosis e hiperplasia micro y macronodular. Algunos tumores producen múltiples hormonas y los pacientes se encuentran en riesgo de desarrollar nuevos tumores, pero la resección de tumores aparentes puede resultar en el control a largo plazo de la endocrinopatía existente. Esto es particularmente cierto en pacientes con insulinoma e hipoglicemia.

Algunos pacientes con gastrinoma también pueden ser considerados para resección de su tumor (es) de células insulares sin gastrectomía concomitante, especialmente cuando el muestreo venoso transhepático demuestra un lugar único de excesiva producción de gastrina. Sin embargo, si el muestreo venoso transhepático demuestra fuentes difusas de hipergastrinemia, un procedimiento de resección pancreática local invariablemente fallará. La pancreatectomía total en pacientes con síndrome NEM I con enfermedad localizada del páncreas es el único procedimiento quirúrgico curativo pero está rara vez indicado.

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Authors and Affiliations

  1. Department of Surgery, Division of Endocrine Surgery, The University of Michigan, D2227 South Ambulatory Care Building, 48109, Ann Arbor, Michigan, USA

    Norman W. Thompson M.D. (Chief), Ricardo V. Lloyd M.D., Ronald H. Nishiyama M.D., Aaron I. Vinik M.D., William E. Strodel M.D., Maria D. Allo M.D., Frederic E. Eckhauser M.D., Gary Talpos M.D. & Tim Mervak M.D.

  2. Department of Pathology, The University of Michigan, Ann Arbor, Michigan, USA

    Norman W. Thompson M.D. (Chief), Ricardo V. Lloyd M.D., Ronald H. Nishiyama M.D., Aaron I. Vinik M.D., William E. Strodel M.D., Maria D. Allo M.D., Frederic E. Eckhauser M.D., Gary Talpos M.D. & Tim Mervak M.D.

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  1. Norman W. Thompson M.D.
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  2. Ricardo V. Lloyd M.D.
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  3. Ronald H. Nishiyama M.D.
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  4. Aaron I. Vinik M.D.
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Thompson, N.W., Lloyd, R.V., Nishiyama, R.H. et al. MEN I pancreas: A histological and immunohistochemical study. World J. Surg. 8, 561–572 (1984). https://doi.org/10.1007/BF01654938

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