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Pathologic Features of Prognostic Significance in Adrenocortical Carcinoma
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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“A threshold above a Weiss score of 3 (also on the modified score) was associated with an increased risk of malignant behavior (112).”
From Adrenal incidentaloma (2020) · cites this paper as [112]
In the citing paper
“In the initial study by Weiss, the features with the strongest association to outcome were the mitotic rate >5/50 high powered field, atypical mitoses, and venous invasion (111) and in the second study by Weiss in 1989 the strongest association with patient outcome was the mitotic rate (112).”
From Adrenal incidentaloma (2020) · cites this paper as [112]
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“The diagnosis of adult primary adrenocortical neoplasms, namely adrenocortical adenoma (ACA) and carcinoma (ACC), has been relying on the classical nine morphological parameters of the Weiss System [20] and its modifications [21] for more than forty years.”
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“The presence of any one of the major criteria indicates malignancy, the presence of one to four minor criteria is indicative of uncertain malignant potential, whereas the absence of all major and minor criteria indicates benign behavior.[5]”
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“Adrenocortical carcinoma (ACC) is a rare malignant tumor that arises in the adrenal cortex and has a very poor prognosis (4).”
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Self-citationAldosterone‐Producing Adrenocortical Carcinoma Metastases Found Seven Years After Adrenalectomy
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“In our case, six of nine criteria were satisfied, and the patient was diagnosed with a malignant tumor [12] (Table 2).”
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“(35) proposed the mitotic rate as a useful index, whereas others proposed tumor size and weight, as well as tumor necrosis and mitotic counting as reliable prognostic factors (39).”
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“This grading system has originally been proposed by Weiss in 1989 [33] and has since been validated in several adult patients’ cohorts [32, 37, 60] proving to carry a significant prognostic value [33, 37].”
InfluentialPotent antitumor activity of HSP90 inhibitor AUY922 in adrenocortical carcinoma
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“Histological features, including high mitotic rate, atypical mitoses, high nuclear grade, low percentage of clear cells, necrosis, diffuse architecture of tumor, capsular invasion, sinusoidal invasion, and venous invasion, are carefully analyzed according to the method of Weiss and Medeiros [10].”
MethodRetractedRecent developments in canine Cushing`s syndrome
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“Weiss's criteria score [10] for her ACC was 6 out of a maximum score of 9.”
BackgroundAdrenocortical Carcinoma - A 25 Years Tertiary Centre Experience and Short Review of the Literature
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“The diagnosis of malignancy in adrenal cortical tumours is based on invasion of local structures and metastasis [22] and several scores have been proposed, the most popular one being Weiss score [23].”
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A case of adrenocortical carcinoma diagnosed 9 years after the discovery of adrenal incidentaloma
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“The immune score of TCGA ACC tumor [16] samples based on CIBERSORTx algorithm (*** p-value = 0.”
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“The tumor was considered an adrenocortical adenoma according to the criteria of Weiss (7-9).”
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“[14] suggested that at least 4 of their list of 9 pathologic criteria are required for a diagnosis of malignancy in ACT.”
BackgroundA current perspective on treatment of adrenocortical carcinoma
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“Almost all of the previous studies lacked a concomitant control group of untreated patients with comparable baseline characteristics and only four of them have included > 20 patients [11,22-24].”
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Diagnostic Role of Prostate-Specific Membrane Antigen in Adrenocortical Carcinoma
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“TheWeiss (7) criteria are used to diagnose ACC in adults; however, in some cases, the diagnosis of malignancy is not straightforward.”
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Self-citationExpression of telomerase (hTERT) in aldosterone-producing adrenocortical tumors
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“The following parameters, derived from the Weiss criteria (31) (tumor extension, nuclear atypia, necrosis, fibrosis, capsule, pushing edges, multiples nodules, zona fasciculata-like cells, zona glomerulosa-like cells, compact reticular cells, hybrid cells, oncocytes and balloon cells), were determined in a blinded man…”
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“By modifying the criteria proposed by Weiss et al [7], Ribeiro et al. [12] subdivided paediatric ACC into low and high grades.”
BackgroundMethodFunctional Imaging of Adrenocortical Carcinoma
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“Therefore, the current WHO classification of endocrine tumors [1] endorses the application of multiparameter scoring systems, including the Weiss criteria [2,3], modified Weiss criteria [4], Helsinki criteria [5], and reticulin algorithm [6] for adults, and the Lin–Weiss–Bisceglia criteria [7] for oncocytic ACN and Wi…”
MethodAdrenal cyst presenting with clinical features of a pheochromocytoma
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“These 2 adrenal lesions are distinguished histologically using the Weiss Scoring system, a standardized system consisting of 9 pathological criteria to differentiate adenoma from ACC [34 ,35] .”
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“Other major prognostic factors include resection status [11-13], Ki67 index [8,14-16], and mitotic counts [8,27].”
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Primary Adrenocortical Carcinoma
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“The system of Weiss, which is most commonly used, has been developed for distinguishing benign from malignant adrenocortical neoplasms [20].”
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Novel report of an adrenal adenoma in a newborn
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Le corticosurrénalome chez l’enfant : prise en charge actuelle et perspectives
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Self-citationEspieira, I., Vidal, P., Ghersevich, M., et al. (2021) · Open Veterinary Journal · doi:10.5455/ovj.2021.v11.i2.17 · Cited by 2
“The reason for not including animal with suspected adrenal carcinoma was that they might not express or overexpress receptors, both MC2R (for ACTH) and aberrant ones (LHR and GIPR), depending on the cell undifferentiating level (Weiss et al., 1989; Galac et al., 2010).”
BackgroundRadiation Therapy for Adrenocortical Carcinoma
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Allegra, S., Puglisi, S., Borin, C., Chiara, F., Basile, V., Calabrese, A., Reimondo, G., & Francia, S. D. (2022) · Biomedicines · doi:10.3390/biomedicines10081873 · Cited by 2
“The considered inclusion criteria were: age ≥ 18 years, histological diagnosis of ACC (Weiss score [23]), ENSAT stage I–III, complete tumor resection (R0 = free resected margins; R1 = microscopic involvement of resected margins; RX = not determined), postoperative follow-up information and regular mitotane therapeutic…”
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Adrenocortical Cancer in Children
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Antígeno nuclear de proliferação celular em tumores de adrenal
Falconi, R. A. R., Martins, A. P., Velludo, M. A., et al. (2000) · Acta Cirúrgica Brasileira · doi:10.1590/s0102-86502000000600012 · Cited by 2
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Genetic landscape of sporadic unilateral adrenocortical adenomas without PRKACA p.Leu206Arg mutation
Ronchi, C. L., Di, D. G., Sbiera, S., Assié, G., Weigand, I., Calebiro, D., Appenzeller, S., Rubin, B., Waldmann, J., Scaroni, C. M., et al. (2016) · Endocrine Abstracts · doi:10.1530/endoabs.41.oc1.1 · Cited by 2
Uncommon Adrenal Tumors in Children and Adolescents
Ribeiro, R. C., Galindo, C. R., Pinto, E. M., Zambetti, G. P., & de Figueiredo, B. C. (2017) · Wiley eBooks · doi:10.1002/9781119196235.ch77 · Cited by 2
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Kanzawa, M., Watanabe, M., Yamamoto, M., et al. (2025) · Endocrine Journal · doi:10.1507/endocrj.ej24-0687 · Cited by 1
“Criteria such as those of Weiss et al. for adreno‐ cortical tumors emphasize factors such as necrosis, increased mitotic figures, angioinvasion, and a high Ki-67 labeling index rather than sarcomatoid histology [33, 34].”
Kuhlen, M., Wudy, S. A., Baumann, C., Vokuhl, C., Hartmann, M. F., Kunstreich, M., Claus, R., & Redlich, A. (2025) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2025-0198 · Cited by 1
Metadata
- Authors
- Weiss, L. M., Medeiros, L. J., & Vickery, A. L.
- Affiliations
- Stanford University (US)
- Massachusetts General Hospital (US)
- Venue
- The American Journal of Surgical Pathology
- Published
- 1989-03
- Volume
- 13
- Issue
- 3
- Pages
- 202-206
- ISSN
- 0147-5185 (ISSN-L)
- 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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