Cited by 818Adrenal and Paraganglionic TumorsRenal cell carcinoma treatmentSarcoma Diagnosis and Treatment

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Pathologic Features of Prognostic Significance in Adrenocortical Carcinoma

Weiss, Lawrence M., Medeiros, L. Jeffrey, Vickery, Austin L.·1989·The American Journal of Surgical Pathology

DOI 10.1097/00000478-198903000-00004

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Abstract

There are currently no well-established pathologic prognostic factors helpful in distinguishing low versus high grade adrenocortical carcinomas. The effect of 11 pathologic parameters on survival was investigated in 42 cases of adrenocortical carcinoma. Only one variable, mitotic rate, had a strong statistical association with patient outcome. The 21 patients with carcinomas with greater than 20 mitoses per 50 high power fields (hpf) had a median survival of 14 months, whereas the 21 patients with carcinomas with less than or equal to 20 mitoses had a median survival of 58 months (p less than 0.02). The presence of atypical mitoses, capsular invasion, tumor weight greater than 250 g, and size greater than 10 cm each showed a marginal statistical association with poor survival (p less than 0.06), whereas other features assessed, such as nuclear grade, presence of necrosis or of venous or sinusoidal invasion, character of the tumor cell cytoplasm, or architectural pattern, showed no statistical significance in predicting survival. It is proposed that adrenal cortical carcinomas with greater than 20 mitoses be designated high grade, whereas tumors with less than or equal to 20 mitoses be designated low grade.

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“[26] and a cortical lesion with a Weiss score exceeding 2 was considered malignant.”
Background
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Method
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Method
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Self-citation
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Self-citation
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“high mitotic count (O20 mitoses per 50 high-power fields; Weiss et al. 1989).”
Background
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“Weiss score 3 (64) and subsequent modifications (3) may not be as accurate for OACT as in conventional ACC.”
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“A mitotic rate of >20 per 50 HPF was associated with lower median survival.(35) A Weiss score of ‡6 correlated with poorer disease-free and overall survival.”
Background
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Tissue Remodelling in the Adrenal Gland
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“Histologic indexes of malignancy that can predict prognosis have been elaborated [3, 11, 12, 32].”
Background
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“All samples with aWeiss score of 4 or above were judged as ACC (Weiss et al. 1989).”
Background
Expression of progesterone and estradiol receptors in normal adrenal cortex, adrenocortical tumors, and primary pigmented nodular adrenocortical disease
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“Also, Weiss and colleagues have mentioned an ACC with 280 mm in dimension in their series published in 1989 [52] but no clinicopathological details about the case.”
BackgroundMethodInfluential
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“Weiss score includes nine criteria of proliferation, nuclear abnormality and tumor extension [54] (Table 1).”
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“It consists of nine morphological parameters and since 1989 a threshold for malignancy of at least three criteria present in the tumor (Weiss et al. 1989).”
Background
Clinical characteristics of small functioning adrenocortical tumors in children
Michalkiewicz, E., Sandrini, R., Bugg, M. F., Cristófani, L. M., Caran, E., Cardoso, A. M. S., de Lacerda, L., & Ribeiro, R. C. (1997) · Medical and Pediatric Oncology · doi:10.1002/(sici)1096-911x(199703)28:3 · Cited by 59
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“!3 were classified as ACA and those with a Weiss score of R3 as ACC (Weiss 1984, Weiss et al. 1989).”
Background
MicroRNA expression patterns in adrenocortical carcinoma variants and clinical pathologic correlations
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“The diagnosis of adrenocortical carcinoma is currently based on the Weiss System [3,4], a scoring procedure that can easily classify most cases, but is particularly challenged in tumors with incomplete morphological signs of malignancy, even if used by experts and specifically trained pathologists [5], and in adrenoco…”
MethodInfluential
Adrenocortical Tumors
Tissier, F., Aubert, S., Leteurtre, E., Ghuzlan, A. A., Patey, M., Decaussin‐Petrucci, M., Doucet, L., Gobet, F., Hoang, C., Mazerolles, C., et al. (2012) · The American Journal of Surgical Pathology · doi:10.1097/pas.0b013e31825a6308 · Cited by 55
“The Weiss system is considered the mainstay in differentiating benign from malignant ACTs in the adult population.(19,31,32) It is the reference method for selecting patients for adjuvant chemotherapy after complete removal of an ACT.”
Method
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Untitled work
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“In this regard, the pathological diagnosis of “carcinoma” requires the recognition of multiple morphological parameters combined either in scoring systems [2-4] or in diagnostic algorithms [5,6,7], suggestive but not pathognomonic per se of malignancy.”
Background
Surgery is associated with improved survival for adrenocortical cancer, even in metastatic disease
Livhits, M. J., Li, N., Yeh, M. W., & Harari, A. (2014) · Surgery · doi:10.1016/j.surg.2014.08.047 · Cited by 55
“It can be approximated using the Weiss criteria, but malignancy is only confirmed when the tumor recurs or metastasizes.(6,7) Therefore, major diagnostic dilemmas arise in the evaluation of patients with solitary adrenal nodules.”
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“The original threshold for malignancy, established in 1984, was the presence of at least four criteria(5); but this was reduced to three or more criteria in 1989 after it was observed that some tumours with a score of 3 had recurred.(6) In 2002, Aubert et al.”
Background
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Oncocytic adrenocortical carcinomas: A pathological and immunohistochemical study of four cases in comparison with conventional adrenocortical carcinomas
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“Tumor weight or tumor size has traditionally been considered as the only valid prognostic parameters, and various cut-offs have been proposed throughout the years [1,4,11,13,22,24,25].”
Background
Pathogenesis of adrenocortical cancer
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IGF2 Promotes Growth of Adrenocortical Carcinoma Cells, but Its Overexpression Does Not Modify Phenotypic and Molecular Features of Adrenocortical Carcinoma
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“This is particularly problematic in pediatric cases as it is clearly established that pediatric ACTs behave differently than their histologically similar adult counterparts and the Weiss criteria [6, 7], most widely used in adult ACTs, often overpredict the diagnosis of malignancy in these tumors.”
Background
Expression of aromatase and estrogen receptors in human adrenocortical tumors
Barzon, L., Masi, G., Pacenti, M., Trevisan, M., Fallo, F., Remo, A., Martignoni, G., Montanaro, D., Pezzi, V., & Palù, G. (2007) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-007-0542-0 · Cited by 52
“[35], with modification proposed by Aubert et al.”
Method
Functioning adrenocortical oncocytoma
Xiao, G., Pertsemlidis, D. S., & Unger, P. D. (2005) · Annals of Diagnostic Pathology · doi:10.1016/j.anndiagpath.2005.05.005 · Cited by 52
“The most widely used histologic criteria proposed by Weiss et al [18] were 3 or more of the following: high nuclear grade, eosinophilic cytoplasm, diffuse architecture, and presence of necrosis, mitotic figures (N5 per 50 high-power fields), atypical mitotic figures, capsular invasion, venous invasion, and sinusoidal…”
Method
Adrenocortical carcinoma: presentation and outcome of a contemporary patient series
Kostiainen, I., Hakaste, L., Kejo, P., Parviainen, H., Laine, T., Löyttyniemi, E., Pennanen, M., Arola, J. T., Haglund, C. H., Heiskanen, I., et al. (2019) · Endocrine · doi:10.1007/s12020-019-01918-9 · Cited by 53
“All cases (Weiss score ≥ 4 [24, 25]) diagnosed between 1 January 2002 and 27 April 2018 were included.”
Background
Profile and outcome of pure androgen-secreting adrenal tumors in women: experience of 21 cases
Moreno, S., Montoya, G., Armstrong, J., Leteurtre, E., Aubert, S., Vantyghem, M.-C., Dewailly, D., Wemeau, J.-L., & Proye, C. (2004) · Surgery · doi:10.1016/j.surg.2004.06.046 · Cited by 51
Adrenocortical carcinoma in children: First population-based clinicopathological study with long-term follow-up
Kerkhofs, T. M. A., Ettaieb, M. H. T., Verhoeven, R. H. A., Kaspers, G. J. L., Tissing, W. J. E., Loeffen, J. L. C., van den Heuvel‐Eibrink, M. M., de Krijger, R. R., & Haak, H. R. (2014) · Oncology Reports · doi:10.3892/or.2014.3506 · Cited by 52
“We direct the reader to the literature for further details (9,10,14).”
Background
Update on the Management of Unusual Neuroendocrine Tumors: Pheochromocytoma and Paraganglioma, Medullary Thyroid Cancer and Adrenocortical Carcinoma
Strosberg, J. (2013) · Seminars in Oncology · doi:10.1053/j.seminoncol.2012.11.009 · Cited by 48
Matrix metalloproteinase type 2 expression in malignant adrenocortical tumors: diagnostic and prognostic significance in a series of 50 adrenocortical carcinomas
Volante, M., Sperone, P., Bollito, E., Frangipane, E., Rosas, R., Daffara, F., Terzolo, M., Berruti, A., & Papotti, M. G. (2006) · Modern Pathology · doi:10.1038/modpathol.3800683 · Cited by 49
Sampling of the adrenal glands by endoscopic ultrasound-guided fine-needle aspiration
Stelow, E. B., Debol, S. M., Stanley, M. W., et al. (2005) · Diagnostic Cytopathology · doi:10.1002/dc.20273 · Cited by 50
Adrenocortical cancer: recent clinical and molecular advances
Sidhu, S. B., Sywak, M. S., Robinson, B. G., & Delbridge, L. (2003) · Current Opinion in Oncology · doi:10.1097/00001622-200401000-00004 · Cited by 51
Diagnostic and prognostic features in adrenocortical carcinoma: a single institution case series and review of the literature
Wanis, K. N., & Kanthan, R. (2015) · World Journal of Surgical Oncology · doi:10.1186/s12957-015-0527-4 · Cited by 49
“Histopathological diagnosis of ACC is made when tumors meet three of the nine Weiss criteria as listed below [21,30,32]: 1) grade 3 or 4 nuclear grade (enlarged, oval to lobulated nuclei with coarsely granular to hyperchromatic chromatin and easily discernible, prominent nucleoli); 2)”
Method
Clinical and Pathophysiological Implications of Chromosomal Alterations in Adrenocortical Tumors: An Integrated Genomic Approach
Barreau, O., de Reyniès, A., Wilmot-Roussel, H., Guillaud-Bataille, M., Auzan, C., René-Corail, F., Tissier, F., Dousset, B. E., BERTAGNA, X. Y., Bertherat, J. Y., et al. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1588 · Cited by 49
Renal and adrenal masses containing fat at MRI: Proposed nomenclature by the society of abdominal radiology disease‐focused panel on renal cell carcinoma
Schieda, N., Davenport, M. S., Pedrosa, I., Shinagare, A. B., Chandarana, H., Curci, N. E., Doshi, A. M., Israel, G. M., Remer, E. M., Wang, J., et al. (2019) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.26542 · Cited by 49
“ACCs usually can be readily differentiated from adenomas based on their large size (>4 cm), heterogeneous appearance, invasive features, and presence of metastatic disease.(2,59) ACC may contain microscopic fat due to fat within tumor cells since they are derived from the adrenal cortex; however, there also are report…”
Mutation and methylation analysis of TP53 in adrenal carcinogenesis
Sidhu, S., Martin, E. W., Gicquel, C., Melki, J. R., Clark, S. J., Campbell, P., Magarey, C. J., Schulte, K., Röher, H.-D., Delbridge, L., et al. (2005) · European Journal of Surgical Oncology · doi:10.1016/j.ejso.2005.01.013 · Cited by 49
The value of dehydroepiandrosterone sulfate measurement in the differentiation between benign and malignant adrenal masses
Terzolo, M., Ali, A., Osella, G., Reimondo, G., Pia, A., Peretti, P., Paccotti, P., & Angeli, A. (2000) · European Journal of Endocrinology · doi:10.1530/eje.0.1420611 · Cited by 47
Adrenocortical tumor in a patient with familial adenomatous polyposis: a case associated with a complete inactivating mutation of the APC gene and unusual histological features
Wakatsuki, S., Sasano, H., Matsui, T., Nagashima, K., Toyota, T., & Horii, A. (1998) · Human Pathology · doi:10.1016/s0046-8177(98)90052-1 · Cited by 49
Preoperative 18F‐FDG Uptake is Strongly Correlated with Malignancy, Weiss Score, and Molecular Markers of Aggressiveness in Adrenal Cortical Tumors
Gust, L., Taïeb, D., Beliard, A., Barlier, A., Morange, I., Micco, C. D., Henry, J., & Sebag, F. A. (2011) · World Journal of Surgery · doi:10.1007/s00268-011-1374-2 · Cited by 48
Significance of heparanase-1 and vascular endothelial growth factor in adrenocortical carcinoma angiogenesis: potential for therapy
Xu, Y., Zhu, Y., Shen, Z., Sheng, J.-Y., He, H., Ma, G., Qi, Y., Zhao, J., Wu, Y., Rui, W., et al. (2011) · Endocrine · doi:10.1007/s12020-011-9502-1 · Cited by 48
“The pathological diagnosis of ACC was based on Weiss’s criteria with its score C3 [21].”
Method
Pathologic features and expression of insulin-like growth factor-2 in adrenocortical neoplasms
Erickson, L. A., Jin, L., Sebo, T. J., Lohse, C., Pankratz, V. S., Kendrick, M. L., van Heerden, J. A., Thompson, G. B., Grant, C. S., & Lloyd, R. V. (2001) · Endocrine Pathology · doi:10.1385/ep:12:4:429 · Cited by 48
Loss of Heterozygosity of 17p13, With Possible Involvement of ACADVL and ALOX15B, in the Pathogenesis of Adrenocortical Tumors
Soon, P. S. H., Libé, R., Benn, D. E., Gill, A. J., Shaw, J., Sywak, M. S., Groussin, L., BERTAGNA, X. Y., Gicquel, C., Bertherat, J. Y., et al. (2008) · Annals of Surgery · doi:10.1097/sla.0b013e318153ff55 · Cited by 48
Senescence-induced immune remodeling facilitates metastatic adrenal cancer in a sex-dimorphic manner
Warde, K. M., Smith, L., Liu, L., Stubben, C., Lohman, B. K., Willett, P. W., Ammer, J. L., Castaneda-Hernandez, G., Imodoye, S. O., Zhang, C., et al. (2023) · Nature Aging · doi:10.1038/s43587-023-00420-2 · Cited by 52
Low expression of HLA‐DRA, HLA‐DPA1, and HLA‐DPB1 is associated with poor prognosis in pediatric adrenocortical tumors (ACT)
Leite, F. A., Lira, R. C. P., Fedatto, P. F., Antonini, S. R. R., Martinelli, C. E., de Castro, M., Neder, L., Ramalho, L. N. Z., Tucci, S., Mastellaro, M. J., et al. (2014) · Pediatric Blood & Cancer · doi:10.1002/pbc.25118 · Cited by 47
“childhood ACT [1,2] and the histopathological diagnosis was made according to the Weiss criteria [21].”
Method
GPER agonist G-1 decreases adrenocortical carcinoma (ACC) cell growthin vitroandin vivo
Chimento, A., Sirianni, R., Casaburi, I., Zolea, F., Rizza, P., Avena, P., Malivindi, R., Luca, A. D., Campana, C., Martire, E., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.4241 · Cited by 50
Adrenocortical Carcinoma
Erickson, L. A., Rivera, M., & Zhang, J. (2014) · Advances in Anatomic Pathology · doi:10.1097/pap.0000000000000019 · Cited by 47
Next-generation sequencing reveals microRNA markers of adrenocortical tumors malignancy
Koperski, Ł., Kotlarek, M., Świerniak, M., Kolanowska, M., Kubiak, A., Górnicka, B., Jażdżewski, K., & Wójcicka, A. (2017) · Oncotarget · doi:10.18632/oncotarget.16788 · Cited by 47
“The Weiss score (WS) is currently the most commonly used and the most validated system [4, 5] but its biggest drawback is the great subjectivity in the evaluation and relatively low reliability of certain microscopic criteria.”
BackgroundMethod
Primary malignant tumors of the adrenal glands
Almeida, M. Q., Neto, J. E. B., Mendonca, B. B., Latronico, A. C., & Fragoso, M. C. B. V. (2018) · Clinics · doi:10.6061/clinics/2018/e756s · Cited by 46
“A careful histopathological evaluation is critical for the correct diagnosis of adrenal tumors, especially for neoplasms localized to the adrenal gland (24).”
Background
A Diagnostic Approach to Adrenocortical Tumors
Hodgson, A., Pakbaz, S., & Mete, Ö. (2019) · Surgical pathology clinics · doi:10.1016/j.path.2019.08.005 · Cited by 48
Adrenocortical tumours in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations
Virgone, C., Roganović, J., Vorwerk, P., Redlich, A., Schneider, D. T., Janić, D., Bień, E., Almaraz, R. L., Godzinski, J. K., Österlundh, G., et al. (2021) · Pediatric Blood & Cancer · doi:10.1002/pbc.29025 · Cited by 48
Specific MicroRNAs Differentiate Adrenocortical Adenomas from Carcinomas and Correlate With Weiss Histopathologic System
Feinmesser, M., Benbassat, C. A., Meiri, E., Benjamin, H., Lebanony, D., Lebenthal, Y., de Vries, L., Drozd, T., & Spector, Y. (2014) · Applied immunohistochemistry & molecular morphology · doi:10.1097/pai.0000000000000117 · Cited by 46
A surgical approach to adrenocortical tumors in children: the mainstay of treatment
Stewart, J. N., Flageole, H., & Kavan, P. (2004) · Journal of Pediatric Surgery · doi:10.1016/j.jpedsurg.2004.01.029 · Cited by 46
Adrenocortical oncocytoma: a case report and review of literature
Tahar, G., Nejib, K. N., Sadok, S. S., et al. (2008) · Journal of Pediatric Surgery · doi:10.1016/j.jpedsurg.2007.12.067 · Cited by 46
Adrenal Cortical Carcinoma—Review of Current Knowledge and Treatment Practices
Phan, A. T. (2007) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2007.04.007 · Cited by 45
Adrenocortical carcinoma producing 11-deoxycorticosterone: a rare cause of mineralocorticoid hypertension
Müssig, K., Wehrmann, M., Horger, M., Maser-Gluth, C., Häring, H.-U., & Overkamp, D. (2005) · Journal of Endocrinological Investigation · doi:10.1007/bf03345531 · Cited by 43

Authors: Weiss, L. M., Medeiros, L. J., & Vickery, A. L.
Affiliations: Stanford University (US)
Massachusetts General Hospital (US)
ORCID: Weiss, Lawrence M.
Medeiros, L. Jeffrey
Venue: The American Journal of Surgical Pathology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 1989-03
Volume: 13
Issue: 3
Pages: 202-206
ISSN: 0147-5185 (ISSN-L)
DOI: 10.1097/00000478-198903000-00004
OpenAlex: W2023370041
Cited by: 818
References: 0
Citations by year: 2026: 13 · 2025: 21 · 2024: 19 · 2023: 20 · 2022: 33 · 2021: 30 · 2020: 34 · 2019: 22 · 2018: 27 · 2017: 30 · 2016: 31 · 2015: 40 · 2014: 38 · 2013: 33 · 2012: 34
FWCI: 8.11
Type: journal article
Language: en
Open access: closed
Locations: The American Journal of Surgical Pathology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
Health Sciences › Medicine › Oncology › Renal cell carcinoma treatment
Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
Keywords: adrenocortical carcinoma, prognostic factors, mitotic activity, tumor grade, survival, capsular invasion, tumor size, tumor weight, atypical mitoses, venous invasion, nuclear grade, necrosis
MeSH terms: Adolescent, Adrenal Cortex Neoplasms, Adult, Aged, Carcinoma, Child, Humans, Middle Aged, Mitotic Index, Neoplasm Invasiveness, Prognosis

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Pathologic Features of Prognostic Significance in Adrenocortical Carcinoma

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