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INTRODUCTIONLeydig cell tumours are rare and are usuallybenign. They belong to the group of ovariansteroid secreting tumours. They are hormoneproducing and derived from specific stromalcells. The ovarian steroid tumours are dividedinto subtypes according to their cell of originas follows: (i) Stromal luteomas; (ii) Leydigcell tumours; and (iii) Steroid tumours not oth-erwise specified. The Leydig cell tumors havetwo forms; namely the hilus cell tumours whicharise from preexisting normal Leydig cells ofthe hilus1 and the stromal Leydig cell tumours,which take their origin in the cortex or subcor-tical region in the ovary from ovarian stromalcells that have differentiated into Leydig cells.2

Leydig cells of different origin show the fea-tures of lipid cells and they contain crystalloidsof Reinke. The presence of crystalloids is spe-cific and of diagnostic value. We report the oc-currence of Leydig cell tumour in a 35-year-old lady who presented with a history of infer-tility and signs of hirsutism and virilization.

CASE REPORTA 35-year-old lady who was married for thelast 15 years, presented for evaluation of infer-tility. On examination signs of hirsutism andvirilization were noticed. Hair growth on thelower abdomen, scalp hair loss andclitoromegaly was noticed (Figures 1 and 2).She gave a history of experiencing regular

Case Report:Virilizing ovarian Leydig cell tumour

K.V. Murali Mohan,1 V. Shanthi,1 B.A. Rama Krishna,1 P. Niroopama,2 M. Anitha2

Departments of 1Pathology, 2 Obstetrics and Gynaecology, Narayana Medical College, Nellore

ABSTRACTLeydig cell tumours belong to the small group of ovarian steroid tumors, which are hormone producing and derivedfrom specific stromal cells. Morphologically, their endocrine-like structure is characteristic, formed of large, polyhedralcells resembling luteal, adrenocortical and Leydig cells. They contain crystalloids of Reinke in their cytoplasm whichhave diagnostic significance. Patients with these tumours present with androgenic manifestations. We report the occur-rence of Leydig cell tumour in a 35-year-old lady who presented with infertility and hirsutism.Key Words: Leydig cell tumour, Reinke's crystalloidsMurali Mohan KV, Shanthi V, Rama Krishna BA, Niroopama P, Anitha M. Virilizing ovarian Leydig cell tumour. J Clin Sci Res2013;2:101-4.

Corresponding author: Dr Murali Mohan, Professor and Head, Department of Pathology, Narayana Medical College,Nellore, India. e-mail: kuppilimm@gmail.com

Received: 15 October, 2012.

Virilizing ovarian Leydig cell tumour Murali Mohan et al

Figure 1: Clinical photograph showing frontal balding Figure 2: Clinical photograph showing clitoromegaly

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menstrual cycles. No abdominal or pelvic adn-exal masses were palpable.Laboratory studies revealed a normal completeblood count and metabolic profile. Endocrino-logic work up revealed normal hormone levelsexcept for increased levels of total and free tes-tosterone. Ultrasonography revealed a solid le-sion measuring 2 2 1.5 cm in the right ovary;left ovary was normal. Exploratory laparotomywas done and bilateral salpingo-oophorectomywas performed. The specimen was sent for his-topathological examination.Grossly the right ovary showed a well circum-scribed nodular mass measuring 2 1.5 1.5cm with a grey yellow glistening cut-surface(Figure 3). Histopathological examination re-vealed tumour cells arranged in lobules sepa-rated by fibrous septa (Figure 4). The tumourcells were round to polygonal with abundanteosinophilic cytoplasm and round nuclei withprominent nucleoli (Figure 5). Few cells hadvacuolated cytoplasm. Reinke's crystals wereidentified (Figure 6). These findings were sug-gestive of a Leydig cell tumour.

DISCUSSIONMost androgen secreting ovarian tumours aresex cord stromal tumors, which constitute lessthan 5% of all ovarian neoplasms.3 Accordingto the World Health Organization (WHO) his-tologic classification of ovarian tumours, sexcord stromal tumours can be classified as granu-

Figure 3: Operative specimen photograph of right ovaryshowing a well circumscribed nodular mass with greyyellow glistening surface

Figure 4: Photomicrograph showing tumour cells ar-ranged in lobules separated by fibrous septa(Haematoxylin and eosin, 100)

Virilizing ovarian Leydig cell tumour Murali Mohan et al

losa stromal cell tumours, Sertoli stromal celltumours, mixed sex cord stromal tumours andsteroid cell tumours.4 Steroid cell tumours werealso designated as "lipid cell tumours" but thisterm is not recommended because upto 25%of tumours in this category contain little or nolipid.5 The term "steroid cell tumour" has beenaccepted by the WHO because it reflects boththe morphological features of the neoplasticcells and their propensity to secrete steroid hor-mones.Leydig cell tumours are rare ovarian steroid cellneoplasms composed entirely or predominantlyof Leydig cells that contain crystals of Reinke.These tumors account for 15% to 20% of ste-roid cell tumours.6 In the hilar zone, the Leydigcells can be normally found in 80% to 85% ofthe postpubertal ovaries, usually in associationwith non-myelinated nerve fibres. Hilar Leydigcell tumours arise from these preexistingLeydig cells of the hilus and can extend intothe ovarian stroma depending on the size ofthe tumour.6 These tumours are generally be-nign and are usually unilateral. The tumour sizeranges between 1 and 15 cm in diameter but inmajority of cases they are less than 5 cm. Mac-roscopically, they are solid, fleshy and well cir-cumscribed. They appear yellow, orange ormore commonly brownish in colour.7 Reinke'scrystals must be present to classify the tumouras Leydig cell tumour. These are elongated,

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hexagonal eosinophilic crystals present in thecytoplasm or rarely in the nucleus. In their ab-sence, the tumour would be classified as a ste-roid cell tumour not otherwise specified. TheLeydig cell tumour is mainly composed of dif-fusely arranged steroid cells with abundanteosinophilic cytoplasm, round hyperchromaticnuclei and sigle small nucleoli. Other notablefeatures of a Leydig cell tumour include nonmedullated nerve fibres, the tendency for cellsto cluster around vessels and fibrinoid necro-sis of blood vessels walls.Hilus cell tumours are encountered predomi-nantly in postmenopausal women (average age58 years) and cause hirsutism and/or viriliza-tion in 75% of cases. These tumours secretetestosterone and occasionally oestrogenic ac-tivity may be observed. The androgenic mani-festations are milder than those associated withSertoli-Leydig cell androblastomas and theironset is less abrupt. Patients with these tumoursusually present with signs of virilization, in-cluding severe hirsutism, frontal balding,clitoromegaly, increased libido, altered bodyfat, increased muscle mass, breast atrophy,deepening of voice and pustular acne.6 Oestro-genic manifestations, such as irregular mensesor postmenopausal bleeding have also beenreported.8

The stromal-Leydig cell tumours take their ori-gin in the cortex or subcortical region in the

ovary from ovarian stromal cells, which havedifferentiated into Leydig cells. They are veryrare benign tumours. Like hilus tumours theyalso occur in postmenopausal patients and areunilateral. Macroscopically these tumours aremultinodular and lobulated and have greatestdimensions of two to five cms. Microscopicexamination show nests of Leydig cells ad-mixed with ovoid and spindle shaped cells,which show the appearances of stromalhyperthecosis or thecoma. Presence of detect-able crystalloid of Reinke is required for iden-tification of Leydig cells of stromal origin.The differential diagnosis of the Leydig celltumours includes ovarian neoplasms contain-ing Leydig cells or luteinized stromal cells. Ser-toli-Leydig cell androblastoma occasionally ex-hibits predominance of Leydig cell component.But presence of Sertoli cells excludes the di-agnosis of pure Leydig cell neoplasm. Lutein-ized stromal cells are very much similar to theLeydig cells but the presence of Reinke's crys-talloids help in the diagnosis. Stromal luteomais a distinct type of steroid tumours arising inthe ovarian stroma which resembles Leydig cellneoplasms. Grossly both the tumours are in-distinguishable but the presence of crystalloidshelps in the correct diagnosis.Androgen producing tumours should be sus-pected in women with virilizing clinical symp-toms and high testosterone levels. Sertoli

Virilizing ovarian Leydig cell tumour Murali Mohan et al

Figure 5: Photomicrograph showing round to polygo-nal tumour cells with abundant eosinophilic cytoplasmand round nuclei (Haematoxylin and eosin, 600)

Figure 6: Photomicrograph showing tumour cellswith Reinke's crystals (Haematoxylin and eosin, 800)

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Leydig cell tumours are larger and usuallyfound easily on imaging, whereas hilar Leydigcell tumours are smaller and often difficult tofind on imaging. If clinical suspicion is highexploratory laparotomy is indicated. It is note-worthy that in this era where sophisticated andexpensive histopathological methods includingimmunohistochemistry are available, this rareand benign tumour can be diagnosed with highaccuracy on good quality haematoxylin andeosin stained slides.

REFERENCES1. Paraskevas M, Scully RE. Hilus cell tumor of the

ovary. A clinicopathological analysis of twelveReinke crystal - positive cases and nine crystal nega-tive cases. Int J Gynecol Pathol 1989;8:299-310.

2. Zhang J, Young RH, Arseneau J, Scully RE. Ova-rian Stromal tumors containing lutein or leydig cells(luteinized thecomas and stromal leydig tumors)--aclinicopathological analysis of fifty cases. Int JGynecol Pathol 1982;1:270-85.

3. Cronje H S, Niemond I, Barn R H, Woodruff JD.Review of the granulose - The carcinoma cell tu-

mors from the Emil Novak Ovarian tumor registry.Am J Obstet Gynecol 1999;180:325-7.

4. Tavassoli FA, Devilee P, Editors. World Health Or-ganization Classification of tumors. pathology andgenetics of tumors of the breast and femal genitalorgans. Lyon: IARC Press; 2003.

5. Scully RE, Young RH, Clement PB. Atlas of tumorpathology tumors of the ovary. maldeveloped go-nads, fallopian tubes and broad ligament 3rd edi-tion. AFIP; Washington, DC 1998.

6. Gershenson DM, Young RH. Ovarian sexcord stro-mal tumors. In: Hoskins WJ, editor. Principles andpractice of gynecologic oncology. 4th edition. Phila-delphia: Lippincott Williams and Wilkins;2005:1024.

7. Paraskevas M, Scully RE. Hilus cell tumor of theovary. A clinicopathological analysis of 12 Reinkecrystal-positive and nine crystal negative cases. IntJ Gynecol Pathol 1989;8:299-310.

8. Ichinohasama R, Teshima S, Kishi K, Mukai K,Tsunemastu R, Ishii-Ohba H, et al. Leydig cell tu-mor of the ovary associated with endometrial carci-noma and containing 17 beta-hydroxy steroid dehy-drogenase. Int J Gynecol Pathol 1989;8:64-71.

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