A 17 year old girl with gradual swelling of lower abdomen

This article has no abstract. The first 100 words appear below:A 17 year old girl presented at the outpatient department with the history of gradual swelling of lower abdomen, early onset of menstruation (precocious puberty) at the age of 7 years followed by secondary amenorrhea for 10 years, growth retardation and breast atrophy. She also complained that her secondary sexual characteristic did not develop. She had no family history of growth retardation or precocious puberty. Her breast showed infantile growth. She had no history of fever, abdominal pain, alteration of bowel habit, weight loss, or loss of appetite. On examination, she was afebrile and vitally stable.


Presentation of Case
Dr. Sayada Fatema Khatun: A 17 year old girl presented at the outpatient department with the history of gradual swelling of lower abdomen, early onset of menstruation (precocious puberty) at the age of 7 years followed by secondary amenorrhea for 10 years, growth retardation and breast atrophy.She also complained that her secondary sexual characteristic did not develop.She had no family history of growth retardation or precocious puberty.Her breast showed infantile growth.She had no history of fever, abdominal pain, alteration of bowel habit, weight loss, or loss of appetite.On examination, she was afebrile and vitally stable.Her height was three feet and nine inch (severely stunted) and underweight (25 kg).Per vaginal examination revealed no pubic hair.No lymph node was enlarged.Neurological, cardiovascular and other systems revealed no abnormality.She was intelligent.Per abdominal examination revealed a lump in the hypogastrium about 16 weeks in size, firm in consistency, non-tender, smooth surfaced, well defined margin, and round in shape.There was no ascites.Her serum estrogen and testosterone levels were increased.Other hormones like follicle stimulating hormone, luteinizing hormone, prolactin, dihydroepiandosterone and progesterone were within the normal limit.Karyotyping and intravenous urogram were normal.Ultrasonography findings showed right adrenal mass (3 x 4 cm) with uterine myoma (7.4 x 6.3 cm).CT scan of the whole abdomen showed the same result.After evaluating the clinical data, physical findings and investigation results, the case was provisionally diagnosed.

Differential Diagnosis
Dr. Jannatul Ferdous: Patient Presented with lower midline swelling and secondary amenorrhea.So, there may be a differential diagnosis of uterine myoma.

Uterine myoma
In this case, clinical features, ultrasonography and CT scan findings indicate it as a case of uterine myoma.But her hormone profiles showed increase serum estrogen and testosterone levels.In juvenile granulosa cell tumor, there may be associated uterine myoma or endometrial hyperplasia or abnormal uterine bleeding due to excessive estrogen level.The ultimate final diagnosis is done by histopathological analysis.

Dr. Khairun Nahar:
As there was increased level of serum testosterone and estrogen, other differential diagnosis may be granulosa cell tumor, thecoma, fibroma, androblastoma and gynandroblastoma.However, histopathology of Call-Exner bodies, nuclear grooves and immunohistochemistry markers help in ruling out the differentials. 1-3

Granulosa cell tumor
Granulosa cell tumor is an uncommon neoplasm.It is two types: Adult and juvenile form.Adult form is slowly progressive and diagnosed in early stage.Juvenile form is more aggressive.Long term follow up is necessary in both types because of recurrences.Histopathology and immunohistochemistry are necessary in both these types for the final diagnosis.Both serum estrogen and testosterone levels are increased in granulosa cell tumor.

Ovarian thecoma
Thecal component was seen along with granulosa cell tumor but it is necessary of the presence of more than 25% of thecal cells in case of thecoma.Thecoma is a benign condition with good prognosis. 4e immunohistochemistry markers valuable in this entity are the vimentin, CD99 and inhibin. 2

Fibroma
Fibroma is usually observed in post-menopausal women.It is derived from the stromal cells and thecoma is similar to fibroma.In fibromas, there is increased cellularity and pleomorphism.

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Gynandroblastoma
This is a very rare type of tumor.It contains both granulosa cell (estrogenic) or Sertoli-Leydig cell (androgenic) types.Usually it is a benign tumor.

Discussion
Rokitansky described granulosa cell tumor first time in 1855. 5According to their appearance near the granulosa cell and ovarian follicles, WHO describes them.They occur in peri-and postmenopausal women aged between 50 to 55 years.Another pick frequency is pre-pubertal age. 6, 7 Abdominal pain (30-50%), abdomi-nal distension due to mass and hormonal events such as 40% develop irregular menstruation, inter-menstrual bleeding or amenorrhea. 8However, clinical examination is very important for asymptomatic patient. 9About 66% patients show endocrine manifestations.This manifestations are due to excess secretion of estrogen and androgen.This explain why endrometrial adenocarcinoma are frequently associated with granulosa cell tumor (5-35%). 7, 8, 10Present of pseudopuberty is a characteristics form of juvenile granulosa cell tumor. 11, 12Galactorrhea or breast atrophy may complete the clinical presentation.

Dr. Ferdous:
The diagnosis is confirmed by histological analysis.There are five subtypes of adult form.Among which, the most common subtypes is the microfollicular type which is characterized by Call-Exner bodies and cores of coffee beam. 13, 14 In the juvenile from, the architecture is lobulated, Call-Exner bodies are rare and there is increase signs of lutienization. 15e main immunohistochemical markers expressed by these cells are vimentin, CD99 and α-inhibin. 3.Khatun: The traditional treatment modalities are complete excision of the tumor with unilateral salphingo-ophorectomy in case of fertility preservation.Total abdominal histerectomy with bilateral salphingo-ophorectomy if patient's family is completed.Sometimes chemo-or radio-therapy may be needed after surgery.[19] This patient is re-commended for adjuvant chemotherapy at tumor board in this university.Before that patient was advised for estimating the level of inhibin, estradiol and complete blood count.
Dr. Nahar: Laparatomy was done which was followed by myomectomy with right sided salphingoophorectomy with infracolic omentectomy with surgical staging.

Operative findings
The uterus of about 18 weeks in size, a large fibroid was in the posterior uterine wall (5 x 6 cm) in size (Figure 1 HbsAg Negative Urine R/E Normal smooth surfaced.The right ovary was enlarged, size about (5 x 4 cm) in size, irregular surface, hard in consistency, capsule were intact, no ascites.Myomectomy was done and sent for histopathology.Complete abdominal exploration was done.Left ovary was streak.There was no deposit.Both sided pelvic lymph nodes were not enlarged.Peritoneal washing was taken for cytology.
Histopathological findings show that the peritoneal washing was negative for malignant cells.The right ovary showed granulosa cell tumor with foci of pleomorphism with few mitosis (Figure 2).The resected uterus was liomyoma.The omentum was free of tumor.
Dr Ferdous: What is the recurrence rate of juvenile granulosa cell tumor?
Dr. Khatun: Juvenile granulosa cell tumor is rela-tively benign and the survival rate is as high as 97% while the chance of recurrence is higher in adult granulosa cell tumor.
Dr. Latifa: What are the chemotherapy agents prescribed for this patient?
Dr. Khatun: The most widely used chemotherapy regime are BVP (bleomycin, vinblastin, cisplatin) or BEP regime substitute etoposide for vinblastin. 20e hormonal therapy is megestrol and LHRH agonists also has a good responses, specially for recurrent cases. 21,22 ut 70% of granulosa cell tumor secrets the estrogen which is responsible for precocious puberty in juvenile granulosa cell tumor while in case adult granulosa cell tumor, it is responsible for the endometrial hyperplasia, endometrial carcinoma and abnormal uterine bleeding.
Our patient complains of precocious puberty, breast atrophy and stunted growth.Unlike adult granulosa cell tumor, fewer Call-Exner bodies are seen in the juvenile granulosa cell tumor.Morphologically and radiologically it is not possible to differentiate between the two verities.
Dr. Sabera Khatun: How will you do the final diagnosis of this patient?
Dr. Khatun: Both clinical and histopathological guidelines are needed to correctly subcategorize granulosa cell tumors into types and the age cannot be considered as the definite criterion.

Final Diagnosis
Juvenile granulosa cell tumor of right ovary with uterine myoma

Figure 2 :
Figure 2: Multi-layering of the lining epithelium which is present in juvenile granulosa cell tumor (A); Many nuclei show irregular nuclear margins and a few show grooves (B).Call-Exner bodies are seen

Figure 1 :
Figure 1: Right sides salphingo oophorectomy was done due to enlarged right ovary.Uterine myoma was resected (inset) -2018 | Key ords:A do i al s elli g; Gra ulosa ell; Ju e ile; Tu or; Uteri e yo a

Farhad Hossain and Khairun Nahar
A Jour al of Ba ga a dhu Sheikh Muji Medi al U i ersity, Dhaka, Ba gladesh A 17 year old girl with gradual swelling of lower abdomen Sayada Fatema Khatun, Sabera Khatun, A. K. M.