Sertoli-Leydig cell tumor
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]
Synonyms and Keywords: Arrhenoblastoma; Androblastoma; Sertoli-stromal cell tumor; Ovarian androblastoma
Overview
Sertoli-Leydig cell tumors is a group of uncommon sex cord stromal tumors, composed of variable proportions of Sertoli cells, Leydig cells, intermediate and poorly differentiated neoplasms, and primitive gonadal stroma. The majority of Sertoli-Leydig cell tumors are benign, unilateral, and confined to the ovaries. However, approximately 10-20% of Sertoli-Leydig cell tumors can be malignant, and also bilateral. The pathogenesis of Sertoli-Leydig cell tumor is characterized by an excess of testosterone secreted by the tumor, therefore early symptoms of Sertoli-Leydig cell tumor are related to the androgenic activity. Common symptoms, include: temporal hair recession, voice deepening, amenorrhea, and oligomenorrhea. The mainstay of therapy for Sertoli-Leydig cell tumor is platinum-based adjuvant chemotherapy and surgery.[1] Fertility-sparing unilateral salpingo-oophorectomy is the most common approach to the treatment of Sertoli-Leydig cell tumor in young women.
Historical Perspective
- Sertoli-Leydig cells were first discovered by Enrico Sertoli, an Italian physician, in 1865.[2]
Classification
- Sertoli-Leydig cell tumor may be mainly classified according to histopathological features into 4 subtypes:[1]
- Well differentiated
- Intermediately differentiated
- Poorly differentiated
- Retiform
- Variants of Sertoli-Leydig cell tumor, include: pure Sertoli cell tumour of ovary.
Pathophysiology
- The pathogenesis of Sertoli-Leydig cell tumor is characterized by an excess of testosterone secreted by the tumor.[1]
- Germline mutation in the DICER1 gene has been associated with the development of Sertoli-Leydig cell tumor.[2]
- On gross pathology, findings of sertoli-leydig cell tumor, include:[2]
- Golden-yellow blood filled
- Unilocular cyst
- Large size mass
- On microscopic histopathological analysis, findings of Sertoli-Leydig cell tumor, include:[2]
- Leydig cells:
- Polygonal pink cells
- Abundant solid or somewhat granular eosinophilic cytoplasm.
- Round nuclei with fine chromatin and a small or indistinct nucleolus.
- Often in small clusters ~ 5-25 cells/cluster.
- Sertoli cells:
- Pale/clear vacuolated cytoplasm.
- Irregular nuclei with irregular/vacuolated-appearing chromatin.
- Architecture: tubules, cords or sheets.
- Classic Sertoli tubule shows an antipodal arrangement of nuclei
- Inhibin
- Calretinin
- WT-1
- Melan A (MART-1) (hallmark)
- Vimentin
Causes
- There are no known causes of Sertoli-Leydig cell tumor.
Differentiating Sertoli-Leydig Cell Tumor from Other Diseases
- Sertoli-Leydig cell tumor must be differentiated from other diseases that cause acne, hirsutism, and voice deepening, such as:[2]
- Endometrioid carcinoma of the ovary
- Ovarian fibroma
- Ovarian fibrothecoma
- Hypothalamic hamartoma (precocious puberty)
Epidemiology and Demographics
- Sertoli-Leydig cell tumors constitute less than 0.5 percent of ovarian cancers.[3]
Age
- The median age at diagnosis of Sertoli-Leydig cell tumor is 14 years.[2]
- Sertoli-Leydig cell tumor is commonly observed among patients aged 15 to 35 years old.[2]
- Sertoli-Leydig cell tumor is more commonly observed among younger females.
Race
- There is no racial predilection for Sertoli-Leydig cell tumor.
Risk Factors
- There are no known risk factors in the development of Sertoli-Leydig cell tumor.[1]
Natural History, Complications and Prognosis
- The majority of patients with Sertoli-Leydig cell tumor are asymptomatic.
- Early clinical features Sertoli-Leydig cell tumor, include acne, hirsutism, and voice deepening.
- If left untreated, patients with Sertoli-Leydig cell tumor may progress to develop lymph node invasion and metastasis.
- Common complications of Sertoli-Leydig cell tumor, include ovarian torsion or peritoneal metastasis.
- Prognosis is generally good, and the 5 year mortality of patients with benign Sertoli-Leydig cell tumors is approximately 85-90%. For malignant tumors with undifferentiated histology, prognosis is poor.[2]
Diagnosis
Diagnostic Criteria
- The diagnosis of Sertoli-Leydig cell tumor is made with the following diagnostic criteria:[1]
- Elevated serum testosterone level
- Clinical features:
- Progressive masculinization
- Compatible imaging findings
Symptoms
- Sertoli-Leydig cell tumor is usually asymptomatic.
- Symptoms of Sertoli-Leydig cell tumor may include the following:[1]
- Temporal hair recession
- Voice deepening
- Amenorrhea
- Oligomenorrhea
Physical Examination
- Patients with Sertoli-Leydig cell tumor usually are well-appearing.
- Physical examination may be remarkable for the following features:[2]
- Progressive masculinization
- Clitoromegaly
- Increase in musculature
- Acne
- Hirsutism
- Breast atrophy
Laboratory Findings
- Laboratory findings consistent with the diagnosis of Sertoli-Leydig cell tumor, include:[4]
- Elevated serum testosterone level
- Elevated alpha-fetoprotein
Imaging Findings
- On ultrasound, findings of Sertoli-Leydig cell tumor, include:[1]
- Hypoechoic lesion
- Usually solitary, unless part of a syndrome
- Well-defined, enhancing solid mass
- On MRI, findings of Sertoli-Leydig cell tumor, include:[1]
- Limited characterization
- Nonspecific appearance
- The signal intensity on T2-weighted MR images depends on their fibrous content.
- Most tumors demonstrate predominantly low T2 signal intensity with scattered areas of high signal intensity.
Treatment
Medical Therapy
- The mainstay of therapy for Sertoli-Leydig cell tumor is platinum-based adjuvant chemotherapy.[1]
- Common chemotherapy regimens for Sertoli-Leydig cell tumor, include:
- Cisplatin, doxorubicin, cyclophosphamide (PAC)
- Vincristine, actinomycin-D, cyclophosphamide (VAC)
- Bleomycin, etoposide, and cisplatin (BEP)
Surgery
- Surgery is the mainstay of therapy for sertoli-leydig cell tumor.[1]
- Fertility-sparing unilateral salpingo-oophorectomy is the most common approach to the treatment of Sertoli-Leydig cell tumor in females before childbearing.
- Total abdominal hysterectomy with bilateral salpingo-oophorectomy is the most common approach to the treatment of Sertoli-Leydig cell tumor in females after childbearing.
Prevention
- There are no primary preventive measures available for Sertoli-Leydig cell tumor.
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 Sertoli-Leydig Tumor. Wikipedia. https://en.wikipedia.org/wiki/Sertoli%E2%80%93Leydig_cell_tumour Accessed on April 18, 2016
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 Tandon R, Goel P, Saha PK, Takkar N, Punia RP (2007). "A rare ovarian tumor - Sertoli-Leydig cell tumor with heterologous element". MedGenMed. 9 (4): 44. PMC 2234306 Freely accessible. PMID 18311394.
- ↑ DiSaia PJ, Creasman WT. Germ cell, stromal and other ovarian tumors. In: Clinical Gynecologic Oncology, Mosby-Yearbook, 1997. p.351.
- ↑ Liggins CA, Ma LT, Schlumbrecht MP (2016). "Sertoli-Leydig cell tumor of the ovary: A diagnostic dilemma". Gynecol Oncol Rep. 15: 16–9. PMC 4750013 Freely accessible. PMID 26937481. doi:10.1016/j.gore.2015.12.003.
