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Endocrine tumors may present as sporadic events or as part of familial endocrine syndromes. Familial endocrine syndromes (or inherited tumor/neoplasm syndromes) are characterized by multiple tumors in multiple organs. Some morphologic findings in endocrine tumor histopathology may prompt the possibility of familial endocrine syndromes, and these recognized histologic features may lead to further molecular genetic evaluation of the patient and family members. Subsequent evaluation for these syndromes in asymptomatic patients and family members may then be performed by genetic screening.

e13014 Background: Adrenocortical Carcinoma (ACC) is a rare endocrine tumor with poor overall prognosis and slight overrepresentation in females. In children, ACC is associated with inherited cancers, predominantly Li-Fraumeni syndrome, with 50-80% of childhood ACC harboring TP53 germline mutations. ACC in AYA are rarely due to germline TP53 mutations; IGF2, PRKAR1A and MEN1 are other less common germline mutated genes in this age group. Methods: We analyzed exome sequencing data from 21 children (C, < 15y), 32 AYA (15-39y), and 60 adult patients ( > 39y) with ACC, originating from the Cleveland Clinic, and TCGA and St. Jude’s datasets. We utilized the Integrative Variant Analysis platform to classify variants based on the American College of Medical Genetics guidelines. We retained all pathogenic, likely pathogenic, and highly-prioritized Variants of Uncertain Significance. Results: Pathway analysis on prioritized variants showed EGFR and p53 pathways as the two top pathways among our C-AYA patients. We found that 4.8% of children and 6.2% of AYA, all female patients, harbored a non-kinase-domain germline EGFR mutation, compared to only 1.7% of adult patients with ACC. As proof-of-principle functional validation, we engineered a lentiviral-mutant stable ACC-cell line, harboring an EGFR variant from a 21 y/o female with aggressive bilateral ACC (p.Asp1080Asn), without germline TP53 mutation. We showed that mutant cells grow slower, yet migrate faster and are characterized by a stem-like phenotype compared to wildtype cells. Osimertinib, among all tested EGFR inhibitors, resulted in the highest growth inhibition of mutant cells. While EGFR inhibitors had no effect on the stemness of mutant cells, Sunitinib, a multi-receptor tyrosine kinase inhibitor, significantly reduced the stem-like behavior. Conclusions: Our data suggest that EGFR is a novel underlying germline predisposition factor for ACC, especially in the female C-AYA population. Although our pre-clinical observations need to be further validated, identifying a targetable gene for ACC has the potential to improve precision oncology management of this disease, which is known to have limited therapeutic options.

Malignant insulinoma is an infrequent functional endocrine tumor of the pancreas. Adequate therapy is a demanding challenge for oncologists and endocrinologists. To evaluate the results of multidisciplinary management of malignant insulinoma. Retrospective review of patients with malignant insulinoma treated from 1995 to 2011. Seven patients with malignant insulinoma were included: four males and three females; median age was 61.8 years (range 37-78). Six tumors were sporadic and one was diagnosed in a patient with a type 1 multiple endocrine neoplasia (MEN-1). Surgery was performed in six cases and one patient was considered unresectable. Hypoglycemias persisted in all cases and somatostatin analogs, glucocorticoids and diazoxide were used. Two patients received everolimus. Other techniques were chemoembolization and internal radiation therapy with yttrium-90. Successful liver transplant was done in the patient with MEN-1. Hypoglycemia management is complex and requires multiple therapies. Further evaluations will be necessary to determine the best treatment.

Adrenocortical carcinoma (ACC) is a rare endocrine tumor with an estimated incidence ranging from one to two per million per year [1], leading to 0.1–0.2 % of cancer deaths [2]. It is one of the most malignant endocrine tumors, with 20–40 % of synchronous metastatic disease at the time of diagnosis [3]. The 5-year overall survival is poor ranging from 30 to 40 % in most series [4–7].

p27Kip1 is a cell cycle regulator firstly identified as a cyclin-dependent kinase inhibitor. For a long time, its function has been associated to cell cycle progression inhibition at G1/S boundary in response to antiproliferative stimuli. The picture resulted complicated by the discovery that p27Kip1 is an intrinsically unstructured protein, with numerous CDK-dependent and -independent functions and involvement in many cellular processes, such as cytoskeleton dynamics and cell motility control, apoptosis and autophagy activation. Depending on the cell context, these activities might turn to be oncogenic and stimulate cancer progression and metastatization. Nevertheless, p27Kip1 role in cancer biology suppression was underscored by myriad data reporting its down-regulation and/or cytoplasmic relocalization in different tumors, while usually no genetic alterations were found in human cancers, making the protein a non-canonical oncosuppressor. Recently, mostly due to advances in genomic analyses, CDKN1B, p27Kip1 encoding gene, has been found mutated in several cancers, thus leading to a profound reappraisal of CDKN1B role in tumorigenesis. This review summarizes the main p27Kip1 features, with major emphasis to its role in cancer biology and to the importance of CDKN1B mutations in tumor development.

Background: Pheochromocytoma is an endocrine tumor that causes hypertension, facial pallor, and headache. Pheochromocytoma patients rarely present with acute heart failure or cardiogenic shock. Method: We discuss the case of a female patient with Takotsubo-pattern cardiomyopathy who presented with acute heart failure caused by pheochromocytoma. Result: Treatment was adjusted based on the data of the pulse contour cardiac output system. After intensive hydration and medication for heart failure, the condition of the patient stabilized. Conclusion: Before confirming the diagnosis, pulse contour cardiac output data could provide a direction for diagnosis and treatment.

The vast array of possible histologies for a given pancreatic mass makes the specific diagnosis of a solid pancreatic mass in an individual patient challenging. This article discusses and reviews the imaging findings of those entities that are likely to be encountered in clinical practice, specifically pancreatic endocrine tumors, solid pseudopapillary tumor, secondary pancreatic masses, and heterotopic spleen.

OBJECTIVE To evaluate the washout (WO) pattern of serous cystadenomas (SCAs) compared with endocrine tumors (ETs) and intraductal papillary mucinous neoplasm (IPMN). METHODS Patients with serous cystadenoma (n = 12), ET (n = 29), and IPMN (n = 35) underwent 4-phase computed tomography CT. Tumors were categorized as hyperdense or hypodense. Computed tomographic values measured were unenhanced attenuation (AU), pancreatic attenuation (A12, 12 seconds), portal attenuation (A35), and equilibrium (A158). Computed tomographic parameters calculated were wash-in (WI) = A12 - AU; WO = A12 - A35; and washout ratio (WOR) = WO/WI × 100/22. RESULTS Hyperdense SCAs had significantly higher WOR than did hyperdense ETs (P = 0.001). Among the 3 hypodense tumors, SCAs had the significantly highest WOR (P < 0.05/3). Relative to the pancreas, the WOR of SCAs were equivalent, whereas the WOR of ETs and IPMNs were significantly lower. CONCLUSIONS Hyperdense SCAs had significantly higher WOR than did hyperdense ETs, and hypodense SCAs had the significantly highest WOR among the three.

The introduction and expansion of laparoscopic and robotic radical retropubic prostatectomy (LRRP and RRRP) for organ-confined prostate cancer have led to an increase in pelvic lymphadenectomy specimens. Extended lymph node dissection (eLND) involves removing nodes over the obturator fossa, external ileac vessels as well as the internal iliac and increases the number of nodes examined. This has the potential to increase incidental nonprostatic nodal pathology identified in prostatectomy specimens. For the first time in the current literature we report the incidental diagnosis of a metastatic small bowel endocrine tumor in a 69-year-old gentleman, made at the time of LRRP and bilateral lymph node dissection. This report suggests that the benefit of an extended lymph node dissection is not only to prostate cancer control and staging, but also to the possibility of diagnosing potentially treatable incidental disease. It is a possibility that both pathologists and urologists alike should be aware of.

The endocrine system is an embryological diverse system consisted of a variety of glands, such as pituitary, parathyroid, thyroid, adrenal, endocrine pancreas, and the diffuse neuroendocrine system. Endocrine tumor can be presented as a sporadic event, or as part of an inherited tumor syndrome. During the past century, inherited tumor syndromes have emerged as an important group of diseases. With the growing knowledge of each inherited tumor syndrome in the molecular genetic level, many changes in clinical management have occurred. This review focuses on the endocrine tumors involving the pituitary, parathyroid, thyroid, adrenal, and endocrine pancreas, in the setting of inherited tumor syndromes. We discuss the specific clinical, molecular genetic, and pathologic features of endocrine tumor in each gland and their associated inherited tumor syndromes. By understanding the pathogenesis of inherited endocrine tumor syndromes and recognizing the unique features of pathologic findings, pathologists bear the responsibility to provide the clinicians the guidelines in terms of screening and treatment of inherited tumor syndromes.

La prise en charge therapeutique des carcinomes endocrines bien differencies (CEBD) localement avances ou metastatiques est complexe, pouvant faire appel a de nombreuses armes therapeutiques (chimiotherapie, immunotherapie, embolisation hepatique, radiotherapie metabolique, etc.), mais reste malheureusement limitee et palliative. Les CEBD presentent la particularite d’avoir un reseau vasculaire tres dense, associe a l’hyperexpression de molecules proangiogeniques dont le vascular endothelial growth factor (VEGF). Par ailleurs, l’insulin growth factor receptor (IGF1-R) ou la perte d’antioncogene (PTEN ou NF1), impliques dans le developpement des CEBD, activent la voie PI3/AKT/mTOR. L’utilisation des therapies ciblant l’angiogenese et la voie mTOR semble donc attractive pour le traitement des CEBD. Cela a ete confirme recemment pour les CEBD pancreatiques avec un doublement de la survie sans progression dans les deux premieres etudes de phase 3 testant l’everolimus ou le sunitinib versus placebo.

La recherche d’une mutation genetique predisposant aux tumeurs hereditaires permet d’organiser une surveillance au long cours et un traitement precoce des tumeurs chez les sujets porteurs de mutation. Un accompagnement psychologique systematique prevu dans un cadre multidisciplinaire, avant la realisation du test genetique et apres l’annonce du resultat, permet de prendre en compte la part subjective associee a une telle demarche et de limiter le traumatisme lie a l’annonce.

Well-differentiated endocrine tumors (WDETs) of the appendix show characteristic morphologic features, including proliferation of cells with finely granulated eosinophilic cytoplasm. However, clear cell WDETs, which can present a diagnostic challenge, have been occasionally described, but it is unknown whether they represent a morphologic variant with distinct clinicopathologic features. Moreover, the clear cell appearance of the cytoplasm has never been explained. We studied 13 appendiceal WDETs composed of clear cells, which showed an immunophenotype identical to that of conventional appendiceal WDETs. Ultrastructural examination demonstrated abundant lipid accumulation. Patient survival was excellent and equal to that of conventional appendiceal WDETs. These neoplasms, which represent a lipid-rich variant of appendiceal WDETs, do not have different relevant clinical implications compared with conventional WDETs, but it is important to know of their existence for the differential diagnosis with more aggressive neoplasms, including goblet cell carcinoids and appendiceal metastases from clear cell carcinomas.

Resume Objectif Les metastases hepatiques des tumeurs endocrines responsables d’un syndrome carcinoide representent une indication potentielle d’embolisation ou chimioembolisation intra-arterielle. Le but de notre etude etait d’evaluer les resultats techniques, cliniques, morphologiques immediats et a distance de ces traitements de 1995 a 2004 dans notre centre. Patients et methode Quatorze patients (huit hommes, six femmes, d’âge moyen 60 ans – de 32 a 80 ans) affectes de metastases hepatiques de tumeurs neuroendocrines et carcinoides symptomatiques, non resecables et ne repondant pas au traitement medical ont ete inclus. Des anthracyclines en emulsion lipiodolee ont ete utilisees 12 fois et une embolisation simple a visee ischemiante par coils et gelatine dans deux cas. Huit patients ont beneficie d’une seule cure, cinq patients de deux cures et un patient de trois cures espacees de un mois chacune. Les criteres d’evaluation morphologiques et cliniques de l’OMS etaient utilises. Resultats Techniquement, l’embolisation a ete realisable dans tous les cas. A cote de symptomes transitoires et de complications mineures (quatre patients), un deces est a deplorer par insuffisance renale aigue. A un mois, l’evaluation du syndrome carcinoide montrait : six reponses cliniques completes, deux ameliorations, trois situations stables et trois evolutions ; morphologiquement : une reponse partielle, sept stabilites et quatre evolutions. Au terme du suivi, cliniquement, huit patients sont decedes en moyenne huit mois apres la premiere cure et six patients ont survecu en moyenne 21 mois apres la premiere cure. Morphologiquement, la progression tumorale etait constante chez tous les patients. Conclusion Conformement aux donnees de la litterature, embolisation et chimioembolisation hepatiques nous paraissent efficaces pour faire face, au moins temporairement, au syndrome carcinoide, compliquant les metastases hepatiques non resecables des TNE, influant qualitativement sur la survie. Nos resultats morphologiques sont en retrait par rapport a ceux publies.

Resume Nous rapportons l’observation d’une patiente âgee de 56 ans chez qui une tumeur pancreatique a ete decouverte fortuitement. La tomodensitometrie montrait une tumeur de la queue du pancreas envahissant la rate et l’estomac, ainsi qu’un thrombus neoplasique du carrefour spleno-mesenterico-portal et des metastases hepatiques bilobaires. Le diagnostic de tumeur endocrine pancreatique metastatique etait retenu. Une strategie chirurgicale a visee curative en deux temps a ete realisee : 1 pancreatectomie gauche elargie, thrombectomie mesenterico-portale et nettoyage du foie gauche ; 2 hepatectomie droite et radiofrequences apres embolisation portale droite. En raison du caractere complet de la resection et des donnees de l’examen histologique, en accord avec le thesaurus national, aucun traitement adjuvant n’a ete prescrit. Le recul sans recidive est de un an.

In a large series of nonselected autopsy investigations an accessory spleen was found in 10–30%. The second most common site is the pancreatic tail (17%). We report a case of intrapancreatic accessory spleen misdiagnosed as a nonsecreting neuroendocrine tumor of the pancreas. Nuclear scintigraphy may provide the definitive diagnosis of an intrapancreatic spleen and therefore prevent patients from unnecessary major surgery.

Thyroid cancer is the endocrine tumor that bears the highest incidence with 33 550 new cases per year. It bears an excellent prognosis with a mortality of 1530 patients per year (Jemal et al.; 2007). We have been treating patients with thyroid carcinoma during many years without many innovations. Recently, we have assisted to the development of new agents for the treatment of this disease with unexpected good results. Here we present a review with the old and new methods for the treatment of this disease.

症例は64歳，男性．他疾患検査中の腹部CTで膵尾部腫瘍を指摘された．手術40日前のMagnetic resonanse cholangiopancreatographyでは主膵管は膵尾部で途絶しているのみで途絶部より乳頭側の膵管に異常は認めなかった．血清ソマトスタチンおよびカルシトニン値の上昇を認めた．膵体尾部脾合併切除を施行した．術中主膵管内に腫瘍栓を認め，2回の追加切除にて断端を陰性にすることができた．切除標本にて腫瘍辺縁から頭側へ約4cmの膵管内腫瘍栓を認めた．組織学的にはwell differentiated endocrine carcinomaで免疫組織学的にソマトスタチン，カルシトニンが陽性であった．本症例は比較的短期間に膵管内腫瘍栓を形成したものと考えられた．臨床的にソマトスタチンおよびカルシトニンを同時に分泌する内分泌腫瘍の報告はまれであり文献的考察を加えた．

Le glucagonome est une tumeur endocrine rare qui se developpe a partir des cellules alpha du pancreas. Il represente 1 % de l’ensemble des tumeurs de l’axe gastroenteropancreatique. Il se caracterise par des manifestations cliniques parmi lesquelles des manifestations cutanees evocatrices: erytheme necrolytique migrateur (ENM), associees a des signes biologiques et radiologiques. Nous rapportons le cas d’un patient âge de 51 ans consultant pour des douleurs de l’hypochondre droit precedees sept mois d’un ENM faisant fortement suspecter un glucagonome. Le bilan biologique a objective une anemie normochrome normocytaire et une hypoprotidemie profonde. Le diagnostic de tumeur caudale du pancreas avec metastases hepatiques a ete obtenu par la TDM abdominale, et la nature endocrine a ete confirmee par la biopsie echoguidee d’un nodule hepatique. Vu la nonresecabilite des metastases hepatiques, le patient a ete propose pour chimiotherapie. Le glucagonome est une tumeur endocrine pancreatique rare a evolution lente, ce qui rend son diagnostic souvent tardif avec presence de metastases dans 80 % des cas lors de sa decouverte. Son traitement curatif demeure essentiellement chirurgical.

Resume Les tumeurs endocrines gastro-intestinales et pancreatiques sont rares et necessitent une approche pluridisciplinaire. Certaines tumeurs endocrines ne se developpent qu’au niveau du pancreas tels que insulinomes, glucagonomes et VIPomes de l’adulte alors que les autres se developpent en dehors du pancreas comme les gastrinomes duodenaux et les somatostatinomes de l’intestin grele. Les manifestations cliniques dependent surtout de la situation de la tumeur et de son caractere fonctionnel ou non. Le diagnostic est souvent tardif au stade metastatique. Les tumeurs fonctionnelles les mieux connues sont celles secretant de la gastrine avec le syndrome de Zollinger-Ellison. L’echoendoscopie est un outil diagnostique de seconde intention. Elle semble particulierement interessante dans les petites tumeurs, en particulier, les insulinomes pancreatiques. Elle a aussi un interet pour le diagnostic de petites tumeurs dans le cadre des neoplasies endocrines multiples de type 1. Le materiel obtenu par aspiration sous echoendoscopie permet d’affirmer le diagnostic et pourrait avoir un interet pronostique.

Eine sekundare Amenorrho kann in seltenen Fallen durch einen endokrinen Tumor ausgelost werden. Dieser Befund erfordert eine enge interdisziplinare Zusammenarbeit zwischen Endokrinologie, Onkologie, Radiologie, Chirurgie und eine referenzpathologische Begutachtung des Tumormaterials. Patienten mit ovariellen Keimstrangstromatumoren sollten gemas der MAKEI-Therapieoptimierungsstudie der GPOH registriert und behandelt werden.

Adrenocortical carcinoma (ACC) is an aggressive endocrine tumor with a poor 5-year survival rate of 10–20%. Current therapy is often ineffective and may be associated with intolerable side effects. Although ACC is extremely rare, recent advances in genomic and expression profiling, coupled with knowledge gained from the study of the inherited syndromes that increase ACC risk, are beginning to bring together a picture of a tumor type dependent on p53, the G2/M cell cycle transition and IGF2 stimulation. Nevertheless, ACC remains a heterogeneous disease. Only recently have sufficient tumors been characterized and results published to permit an exploration of this diversity. Advances in treatment will depend on exploiting those pathways already implicated in ACC, along with those yet to be identified, and testing those treatments in better models of the disease than the three cell lines that currently exist and are widely available to the community.

Carcinoma of unknown primary (CUP) is one of the 10 most frequent cancers worldwide. It constitutes 3-5% of all human malignancies. Patients with CUP present with metastases without an established primary site. CUP manifests as an heterogenous group of mainly epithelial cancers recognised by distinct clinicopathological entities. The diagnostic work-up includes extensive histopathology investigations and modern imaging technology. Nevertheless, the primary tumour remains undetected most of the time. Molecular diagnosis with DNA microarrays demonstrates high sensitivity, but its prognostic contribution is still uncertain. Certain clinicopathological CUP entities are considered as favourable sub-sets responding to systemic platinum-based chemotherapy or managed by locoregional treatment. These sub-sets are: the poorly differentiated carcinomas involving the mediastinal-retroperitoneal nodes, peritoneal papillary serous adenocarcinomatosis in females, poorly differentiated neuroendocrine carcinomas, isolated axillary node adenocarcinomas in females or cervical nodal involvement by a squamous cell carcinoma. Patients who belong to the non-favourable sub-sets have a worse prognosis. © 2008 Elsevier Ireland Ltd. All rights reserved. 69 3 271 278

症例は68歳女性．黄疸の精査のため，当院紹介となった．CT上膵頭部に造影効果を受ける径4cm大の腫瘍を認め，内視鏡では十二指腸乳頭部の開口部より腫瘍が突出しているのが観察された．この部分を内視鏡下に生検することにより，術前に病理学的に非機能性膵内分泌腫瘍の診断を得た． 膵頭部の腫瘍に対して，膵頭十二指腸切除術を行った．病理組織診断では主膵管内に腫瘍が充満し，十二指腸乳頭部の開口部より突出するように進展した，非機能性膵内分泌腫瘍と診断された． 膵内分泌腫瘍は，一般的には膨張発育形式を示すものが多いとされている．膵管内に腫瘍を認めた報告もあるが，主膵管内に充満し，十二指腸乳頭部の開口部より十二指腸内に突出するように進展するものはまれであると考えられるため，若干の文献的考察を加えて報告する．

Gastroenteropancreatic neuroendocrine tumors (GEP NETs) are relatively rare neoplasias arising from the embryonic neural crest, neuroectoderm and endoderm. GEP NETs occur either sporadically or as part of endocrine tumor susceptibility syndromes such as multiple endocrine neoplasia type 1 (MEN1), von Hippel Lindau (VHL) syndrome, neurofibromatosis (NF-1), and possibly tuberous sclerosis (TSC). The overall incidence of GEP NETs shows a significant increase over the past three decades. Improved understanding of the molecular genetics associated with these lesions will likely enhance the diagnosis and treatment of patients with GEP NET.The molecular and clinical genetics of familial GEP NETs have been further elucidated by the characterization of the tumor suppressor genes, MEN1, VHL, NF-1, TSC1, and TSC2. The vastly improved technology in the field of cancer genetics with higher resolution of the study of genetic alterations, and the ability of unbiased mutational analyses of entire tumor genomes is likely to further the understanding of the genetic mechanisms of sporadic GEP NET as well.Recent advances in the molecular genetics of sporadic and familial GEP NET are reviewed.

症例は70代，女性．虚血性大腸炎で入院した際に施行したCTで膵尾部に脾臓への直接浸潤を伴う腫瘤性病変を認めた．EUSでは膵尾部から膵体部へと連続する腫瘤性病変がみられた．ERPで膵頭体移行部にカニ爪様の膵管閉塞像を認め，同部位からの生検でchromograninA陽性，synaptophysin陽性の軽度異型を伴う類円形腫瘍細胞を確認した．以上の所見より主膵管内進展および脾浸潤を伴った膵尾部内分泌腫瘍と診断し，膵体尾部脾合併切除術を施行した．病理組織学的検査では，広範な脾静脈腫瘍栓が逆行性に脾臓内にまで進展していた．また，主膵管内腔に腫瘍細胞の増殖がみられ，主膵管内進展を呈していた．核分裂像は10強拡大視野で10個未満であったが，脾臓への肉眼的進展がみられたことから悪性膵内分泌腫瘍と診断した．術後補助化学療法は未施行であり，11ヵ月間が経過したが，現在無再発生存中である．

A pheochromocytoma is an endocrine tumor that can uniquely mimic numerous stress-associated disorders, with variations in clinical manifestations resulting from different patterns of catecholamine secretion and actions of released catecholamines on physiological systems.

We describe the early and distant results of a 2-step surgical strategy that enables complete resection in selected patients with primary digestive endocrine tumors (DET) and synchronous bilobar liver metastases (LM).Frequent synchronous and bilobar liver involvement limits indications of surgery in LM from DET.From 1996 to 2004, of 41 patients with synchronous bilobar LM from DET, 23 (56%) were selected for 2-step surgery. The first step included resection of the primary tumor and limited (nonanatomic) resection of left LM (segments 1-4) associated with a right portal vein ligation. After 8 weeks, following hypertrophy of the cleared left liver, a right or extended right hepatectomy was planned.At the first step, all primary tumors (bowel = 12, distal pancreas = 10, rectal = 1) were resected and LM were resected in 20 patients (87%). One patient did not have second-step due to tumor progression. The second step (n = 19; 83%) was performed after a median interval of 8 weeks (range, 6-13) and a 54 +/- 21% mean left liver hypertrophy rate. Postoperatively, 4 (17%) and 4 (21%) patients developed nonlethal complications and the median hospital stay was 11 (range, 7-26) and 13 (range, 9-17) days after the first and the second step, respectively. The median number of resected LM was 4 (range, 1-9) and 7 (range, 4-17), respectively. With a median follow-up of 64 months (range, 6-122), of the 19 patients who had complete 2-step surgery, all except one are alive. The 2-, 5-, and 8-year Kaplan-Meier overall and disease-free survival rates were 94%, 94%, 79% and 85%, and 50% and 26%, respectively.This 2-step surgery approach enables complete resection with no mortality, acceptable morbidity, and good long-term survival in selected patients with synchronous bilobar LM from DET.

膵内分泌腫瘍は最近WHOで新たな病理組織学的分類基準が報告された．Well-differentiated endocrine tumor，well-differentiated endocrine carcinoma，poorly-differentiated endocrine carcinoma/小細胞癌，mixed exocrine-endocrine carcinomaの4つの病理組織型に分類し，前2者では更に腫瘍細胞が過剰合成，分泌する膵島ホルモンの種類により細分した．この分類の特徴としては今までその概念が曖昧であった後2者を独立した疾患概念として樹立した事と，well-differentiated tumorを摘出後すなわち術後の臨床経過と関連させて，benign behavior型とuncertain behavior型の2つに分類させた事である．この両者の鑑別は腫瘍径，細胞分裂数，MIB1/Ki67の腫瘍細胞での標識率，脈管，神経への浸潤の有無などの病理組織学的所見に基づいてなされる．これらの指標はいずれも摘出標本を的確に処理しないと正確には得られない所見である事から，膵内分泌腫瘍の患者の診断，治療に従事する者は手術標本の迅速で適切な標本処理が必須である．