Adrenal gland & paraganglia

Adrenal cortical carcinoma

Sarcomatoid



Last author update: 10 January 2022
Last staff update: 2 December 2022

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PubMed Search: Sarcomatoid variant adrenal

Maria Tretiakova, M.D., Ph.D.
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Cite this page: Tretiakova M. Sarcomatoid. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/adrenocorticalcarcinomacarcinosarcoma.html. Accessed December 9th, 2022.
Definition / general
  • Extremely rare malignant tumor of adrenal cortex with biphasic carcinomatous and sarcomatous morphology
Essential features
  • Least common variant of adrenal cortical carcinoma (ACC), ~30 cases reported
  • Sarcomatoid ACC is a particularly aggressive tumor with a dismal prognosis
  • Composed of malignant epithelial adrenocortical cells and specialized mesenchymal elements resembling various sarcomas, often with heterologous features of rhabdomyoblastic, osteogenic, chondroid or PNET-like differentiation
  • Compared to conventional ACC, sarcomatoid variant presents as:
    • Predominately nonfunctioning tumors
    • Predilection for the right adrenal
    • Larger tumor size
    • Higher rate of distant metastases and shorter median survival
    • Older patient population
Terminology
  • Adrenal cortical carcinoma (ACC), sarcomatoid variant
  • Adrenocortical carcinoma, sarcomatoid type
  • Adrenal carcinosarcoma
ICD coding
  • ICD-O: 8370/3 - adrenal cortical carcinoma
Epidemiology
Sites
Pathophysiology
  • 4 theories of sarcomatoid ACC histogenesis (Virchows Arch 2012;460:9):
    • Conversion tumor theory with neoplastic transformation of epithelial to mesenchymal cells
    • Composition tumor theory (paradoxical reactive proliferation of nonepithelial component induced by the epithelial component via paracrine secretion)
    • Collision or biclonal tumor theory (2 synchronous, histologically independent tumors of different clones)
    • Combination or divergent tumor theory (deriving from a common monoclonal stem cell precursor); best supported by molecular studies (Hum Pathol 2016;58:113)
Etiology
Diagrams / tables

Images hosted on other servers:

Survival analysis:
sarcomatoid ACC
versus other
variants

Clinical features
Diagnosis
  • Sarcomatoid ACC on imaging (CT, MRI) has large size, irregular contours, lipid poor characteristics and significant signal heterogeneity (Endocr J 2019;66:739, World J Surg Oncol 2015;13:117)
  • Radiographically and even during gross evaluation, often difficult to confirm adrenal origin due to the advanced presentation
  • By definition, tumor should be composed of adrenocortical epithelial malignant cells and sarcoma-like mesenchymal component on microscopy
  • No minimum percentage of sarcomatoid cells required for the diagnosis (Biomedicines 2021;9:175)
  • Weiss system does not account for sarcomatoid histology and may not be applicable to these tumors, especially the criteria of diffuse architecture (Virchows Arch 2012;460:9)
Laboratory
Radiology description
Radiology images

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CT scan: necrotic areas replacing adrenal gland

Coronal abdominal CT with large adrenal mass

Prognostic factors
Case reports
Treatment
Gross description
Gross images

Image hosted on other servers:

Whitish fleshy, variegated hemorrhagic and necrotic surface

Tumor adherent
to pancreas (A)
and compressing
kidney (B)

Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Maria Tretiakova, M.D., Ph.D.
Sarcomatoid ACC biphasic

Sarcomatoid ACC biphasic

Epithelioid and spindle cells

Epithelioid and spindle cells

Heterologous differentiation

Heterologous differentiation

Positive stains
Electron microscopy description
  • Epithelioid component with tight junctions and abundant mitochondria, similar to conventional ACC
Electron microscopy images

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Epithelioid and spindle cell components

Molecular / cytogenetics description
  • Sarcomatoid ACC had the lowest adrenocortical differentiation scores with very low expression of NR5A1 (SF1 regulator) and steroidogenic enzymes (Cancer Cell 2016;29:723)
  • Wnt beta catenin signaling pathway dysregulation and mutational inactivation of TP53 are common genetic events in sarcomatoid ACC (Histopathology 2018;72:82)
  • Enriched for EMT related markers and stem cell factors that may be associated with the poor prognosis of these tumors and may provide possible therapeutic targets (Histopathology 2018;72:82, Biomedicines 2021;9:175, Hum Pathol 2016;58:113)
  • In differentiated epithelioid component, molecular alterations are similar to conventional ACC including high mutation burden, massive DNA loss followed by whole genome doubling and frequent somatic mutations of P53, CTNNB1, CDKN2A, TERT, ZNRF3, PRKAR1A (Histopathology 2018;72:82, Cancer Cell 2016;30:363)
  • Concordant molecular alterations in phenotypically diverse components (i.e. presence of TP53 and CTNNB1 gene mutations) were detected in 50% of studies by NGS tumors and support a common clonal origin (Hum Pathol 2016;58:113)
Sample pathology report
  • Adrenal gland, right, adrenalectomy:
    • Adrenal cortical carcinoma with the following features:
      • Tumor size: 19 cm x 18 cm x 12 cm
      • Tumor (gland) weight: 600 g
      • Tumor extent: invasion into inferior vena cava and inferior liver surface
      • Histologic type: sarcomatoid variant
      • Histologic grade: high grade
      • Necrosis: present
      • Lymphovascular invasion: present
      • Margins: positive
      • pTNM, AJCC 8th edition: pT4 N0
    • Ancillary studies: Ki67 mitotic rate 40%
Differential diagnosis
Board review style question #1

A 68 year old woman presented with right sided back pain and weight loss. Abdominal ultrasonography and computed tomography (CT) showed the presence of a 12 cm heterogeneous adrenal mass. It was biopsied, showing biphasic morphology with large epithelioid polygonal cells and haphazardly arranged spindle cells. Which statement about this adrenal cortical tumor is accurate?

  1. Pure sarcomatoid morphology is more common than biphasic
  2. Hormonal production is typically abnormal
  3. Clinical presentation and prognosis are similar to conventional adrenocortical carcinoma (ACC)
  4. Adrenocortical immunomarkers are often lost in sarcomatoid areas
  5. Risk of metastatic disease and recurrence is low
Board review style answer #1
D. This is a case of sarcomatoid ACC, an extremely rare malignant tumor with biphasic epithelioid and mesenchymal differentiation. The carcinomatous component is strongly positive for inhibin, MelanA, calretinin and SF1, thus supporting an adrenocortical origin. However, the sarcomatoid component often has a partial or complete loss of adrenocortical markers. Fortunately, > 80% of sarcomatoid ACC has both carcinomatous and sarcomatoid components (A). Functional sarcomatoid ACCs with hormone overproduction are documented in only 11% of cases (B). Compared to conventional ACC, the sarcomatoid variant has a more advanced age at presentation, predominately nonfunctional tumors, predilection of the right side, larger tumor size, higher rate of distant metastases and shorter median survival (C). 75 - 80% of patients with sarcomatoid ACC develop metastases or recurrence within 4 months and have an overall dismal prognosis (E).

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Reference: Adrenal cortical carcinoma, sarcomatoid variant
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