Testis and epididymis
Sex cord stromal tumors
Large cell calcifying Sertoli cell tumor

Author: Swapnil U. Rane, M.D. (see Authors page)

Revised: 18 July 2017, last major update January 2014

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Large cell calcifying Sertoli cell tumor [title]
Cite this page: Large cell calcifying Sertoli cell tumor. PathologyOutlines.com website. http://pathologyoutlines.com/topic/testissertolilargecell.html. Accessed October 22nd, 2017.
Definition / general
Epidemiology
  • Patients usually under age 20 years
  • Part of Carney syndrome with testicular Leydig cell tumors, pituitary tumors, pigmented nodular hyperplasia of adrenal cortex, myxomas of skin, soft tissue, heart and breast
  • Also associated with spotty skin pigmentation (Peutz-Jeghers syndrome)
Sites
  • Normally descended testis
  • Bilateral involvement of testis is common and associated with Carney complex and Peutz-Jeghers syndrome
Pathophysiology
  • Proposed pathogenesis of Large cell calcifying Sertoli cell tumor (LCCSCT), see Pediatr Dev Pathol 2006;9:181:
    • Congenital gene defects of Carney complex or of Peutz-Jeghers syndrome are believed to trigger a cascade of intracellular events that leads to overexpression of aromatase in Sertoli cells, favoring the development of a LCCSCT
    • Though not involved in the genesis of the tumor, a mutational event might induce a higher expression of estrogen receptor (ER)
    • TGFβ1 protein expression is increased in neighboring cells
    • In this environment, TGFβ1 might switch from tumor suppressor to an oncogenic factor and along with estrogen - ER complexes, might favor tumor progression by inhibiting apoptosis
Clinical features
  • Gynecomastia is a common presentation, painless testicular enlargement is less common
  • Bilateral and multifocal tumors point towards syndromic association and should be investigated accordingly
Diagnosis
  • Definite diagnosis can be established only by histopathological examination
Laboratory
  • Serum estradiol levels are commonly increased
Prognostic factors
  • Features associated with malignant behavior (Ulbright: Tumors of the Testis, Adnexa, Spermatic Cord, and Scrotum, First Edition, 1999)
    • Age: mean age of 39 years for malignant tumors versus 17 years for benign tumors
    • Tumor size: larger (mean size 5.4 cm for malignant versus 1.4 cm for benign tumors)
    • Association with syndrome or congenital abnormality (36% for benign versus 12.5% for malignant tumors)
    • Unifocal and unilateral: all reported malignant tumors are unilateral and unifocal but 28% of benign tumors are bilateral or multifocal
  • According to Kratzer et al, tumors should be classified as malignant if they demonstrate ≥ 2 of the following:
    • Spread beyond testis
    • Size > 4 cm
    • Mitoses ≥ 3/10 high power fields
    • Significant nuclear atypia
    • Necrosis
    • Lymphovascular invasion
  • Most patients with a diagnosis of malignant tumor develop retroperitoneal lymph node metastases; many also have hematogenous metastases to bone, liver and lungs
  • Proliferation index is usually 5 - 10% for benign tumors versus ~30% for malignant tumors
  • p53 protein staining does not correlate with malignant behavior
Case reports
Treatment
  • High inguinal orchidectomy is performed routinely
  • There is no role of chemotherapy or radiotherapy in tumors restricted to the testis
  • Role of adjuvant therapy in histologically malignant tumors is not yet established
Gross description
  • Grossly, these tumors average 2 cm in diameter, are often multifocal and are bilateral in about 20% of cases
  • They are well circumscribed and show a white to tan granular cut surface
Gross images

Images hosted on other servers:

Firm, white tan nodules

Tumor

Microscopic (histologic) description
  • Sheets, nests, cords, ribbons and trabeculae of large tumor cells with focal solid tubule formation
  • Foci of intratubular tumor are present in 50%
  • Tumor cells have abundant eosinophilic finely granular cytoplasm
  • Nuclei are round with 1 - 2 small to medium nucleoli and rare mitoses
  • Calcifications are usually prominent with large laminated calcific nodules
    • Psammoma bodies and rarely ossification can be seen
  • Surrounding stroma ranges from myxoid to collagenous
  • Often neutrophilic infiltrate
Microscopic (histologic) images

Images hosted on other servers:

Various images

Sheets with abundant calcifications

Positive stains
Electron microscopy description
  • Charcot-Böttcher crystals are seen but are not specific
Molecular / cytogenetics description
  • No definite chromosomal anomalies have been documented
  • PPKAR1A gene may be mutated even without other clinical manifestations of Carney complex (Hum Pathol 2010;41:552)
Differential diagnosis
  • Leydig cell tumor, NOS: no extensive calcification, MelanA+, usually S100-
  • Leydig cell hyperplasia: extensive lipofuscin pigment, no extensive calcification, S100-
  • Malakoplakia: Michaelis-Gutmann bodies present, inhibin-, calretinin-