Maffucci Syndrome And Associated Morbidities PARASTOU TAVANA MD

Maffucci Syndrome And Associated Morbidities PARASTOU TAVANA. MD PEDIATRIC HEMATOLOGY/ONCOLOGY FELLOWSHIP MOFID CHILDREN HOSPITAL 25 BAHMAN 97

Maffucci syndrome § A 13 -yr-old girl (known case of maffucci syndrome)with irregular menstrual bleeding and abdominal enlargement §at age of 12, she underwent MRI of pelvis due to right hip pain, which showed abnormal bone marrow signals, enchondromatous appearance of femural head and neck § Right femur was more expanded (huge tumor in proximal of femur)

Right femoral biopsy Well differentiated chondrosarcoma Orthopedic consultation observation and follow up

Whole body bone scan Abnormal increased radiotracer uptake of the proximal right humerus, pelvis , (mainly right iliac wing), both femoral bones , tibia bones , right scapula , right radius and ulnar bones Tumoral involvment

Whole body bone scan

Orthopedic consultation Biopsy of right tibia bone(abnormal uptake in bone scan) enchondroma

Tumor markers q. AFP & ß-h. CG: Nl q. CA 19 -9: Increased (112 u/ml) q. CA-125: Nl (22 u/ml)

Right ovarian mass resection § Pathology: Juvenile granulosa cell tumor, Omentum showed microscopic foci of tumoral invasion, Lymph nodes : no significant pathologic change § Mitotic index: 19/10 §Ascites cytology: positive § IHC: Inhibin : positive EMA : negative PAX-8: negative

Tumor markers after surgery q. CA 19 -9: Increased (125 u/ml) q. CA-125: Increased (102 u/ml)

Sonography one week after surgery & before chemotherapy Solid cystic mass in pelvic cavity (100. 70. 55)

FIGO STAGING Stage 2: § The cancer is in one or both ovaries or fallopian tubes and has spread to other organs (such as the uterus, bladder, the sigmoid colon, or the rectum) within the pelvis or there is primary peritoneal cancer (T 2). § It has not spread to nearby lymph nodes (N 0) or to distant sites (M 0).

Evaluation after chemotherapy § Sonography and CT scan and MRI : Nl § Tumor markers: v CA 19 -9: Increased (99 u/ml) 71 v. CA 125: Nl (9. 3 u/ml) 7. 8

Juvenile granulosa cell tumor associated with Ollier disease Enchondromatosis or Ollier disease Incidence: 1 in 100, 000 Generalized mesodermal dysplasia Derangement of cartilaginous growth resulting in incorporation of fragments of the epiphyseal plate within mature bone Indian J Med Paediatr Oncol. 2016 Oct-Dec; 37(4): 293– 295.

Juvenile granulosa cell tumor associated with Ollier disease Maffucci syndrome : q Enchondromatosis is associated with hemangiomas or lymphangiomas q Chondrosarcoma: malignancy in Ollier disease (risk of 30%– 50%) Indian J Med Paediatr Oncol. 2016 Oct-Dec; 37(4): 293295.

primary ovarian malignancies ØEpithelium tumors Ø Germ cell tumors Ø sex cord tumors: Granulosa cells Theca cells Sertoli cells or fibroblasts of gonadal stromal origin

Ovarian Granulosa Cell Tumor: Clinical Features, Treatment, Outcome, and Prognostic Factors §Granulosa cell tumors (most common type of sex cord stromal tumors § 2 -5% of ovarian neoplasms §Mean age at diagnosis : 13 years §Based on histology: Adult (95%) and juvenile (5%) §The majority of patients are diagnosed at early stage and have a relatively favorable prognosis §Clinical : abdominal enlargement , palpable mass, precocious puberty

Ovarian Granulosa Cell Tumor: Clinical Features, Treatment, Outcome, and Prognostic Factors Localized disease stage I tumor(90%) (observation) high risk stage I(adjuvant chemotherapy): large tumor size (≥ 10 -15 cm) stage IC : pre or post operative rupture , malignant ascites high mitotic index(>20/10 hpf ) stage II-IV (postoperative chemotherapy )

Ovarian Granulosa Cell Tumor: Clinical Features, Treatment, Outcome, and Prognostic Factors q Surgical management: stage and age Premenarchal (reproductive years) with early stage: unilateral salpingo-oophorectomy q Postmenopausal: total abdominal hysterectomy and bilateral salpingooophorectomy Department of Radiotherapy and Oncology, Government Medical College and Hospital, Chandigarh, India

Ovarian Granulosa Cell Tumor: Clinical Features, Treatment, Outcome, and Prognostic Factors Stage( most important prognostic factor) 10 -year survivals : 84 -95% for stage I tumors 50 -65% for stage II disease 17 -33% for stages III and IV Department of Radiotherapy and Oncology, Government Medical College and Hospital, Chandigarh, India

Prognostic Value of Ca 125 Levels during Primary Therapy a retrospective analysis : Ca 125 level in 197 patients with epithelial ovarian cancer followed up for an average of three years (1990 -2000. ) Levels around 100 U/l after treatment are indicative of a bad prognosis University of Rostock, Südring 81, 18059 Rostock, Germany

The association of enchondromatosis with malignant transformed chondrosarcoma and ovarian juvenile granulosa cell tumor (Ollier disease) A 22 -year-old patient with Ollier disease (diagnosed at 6 months of age ) pelvic pain and a palpable ovarian mass right-side sonography: well-encapsulated multi locular-solid tumor 113 mm 95 mm 90 mm , tumor originating from the right ovary histological report : juvenile granulosa cell tumor International Federation of Gynecology and Obstetrics (FIGO) Stage IC Taiwanese Journal of Obstetrics & Gynecology(2017)

The association of enchondromatosis with malignant transformed chondrosarcoma and ovarian juvenile granulosa cell tumor (Ollier disease) Sonography of right groin : a large soft-tissue tumor (91. 60. 63 )soft tissue component of an enchondroma originating from the trochanter tuberosity with the osteolysis malignant transformation of enchondroma Taiwanese Journal of Obstetrics & Gynecology(2017)

The association of enchondromatosis with malignant transformed chondrosarcoma and ovarian juvenile granulosa cell tumor (Ollier disease) Bone Tumor Center: wide resection of the extraosseal soft tissue tumor and the major part of the lesser trochanter followed by curettage sampling of the greater trochanter chondrosarcoma Grade 2 4 years after first diagnosis and oncological treatment : complete remission Taiwanese Journal of Obstetrics & Gynecology(2017)

Juvenile granulosa cell tumor associated with Ollier disease A 2. 5 -year-old female child with precocious puberty mass was felt in the right hypochondrium MRI : well-defined right ovarian mass measuring 10 cm × 5 cm × 11 cm with cystic and necrotic areas Indian J Med Paediatr Oncol. 2016 Oct-Dec; 37(4): 293– 295

Juvenile granulosa cell tumor associated with Ollier disease Another incidental finding : multiple small leisions in right femoral neck, greater and lesser trochanter, and the right iliac blade metastatic lesions? ovarian tumor : surgically removed Indian J Med Paediatr Oncol. 2016 Oct-Dec; 37(4): 293– 295

islands of granulosa cells showed Call-Exner bodies

Juvenile granulosa cell tumor associated with Ollier disease Bone scan : no evidence of osteoblastic skeletal metastasis biopsy of the bone lesions : enchondromas significant regression of the breast size and pubic hair (few weeks after the surgery) chemotherapy : germ cell tumor protocol parents : risk for the development of chondrosarcoma and the need for regular follow-up Indian J Med Paediatr Oncol. 2016 Oct-Dec; 37(4): 293– 295