Asia-Oceania J. Obstet. Gynaecol. Vol. 18, No. 4: 309-313 1992
Bone Metastasis in Ovarian Cancer
Lalit Kumar,') V. L. Bhargava?) R. C. Keshav Rao,s) G. K. Rath,') and S. P. Kataria') 1 ) Department of Medical Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences,
New Delhi, India 2) Department of Gynaecology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New
Delhi, India 3) Department of Radiodiagnoris, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences,
New Delhi, India 4 ) Department of Radiotherapy, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, N m Delhi, India
Abstract Bone involvement in carcinoma of ovary occurs rarely. In a review of 103 patients over last 3 years we have seen 4 such patients (serous-2, mucinous-1, mixed germ cell tumour-1). Patients presented with severe localized bone pain, bony swelling and difficulty in walking. The common sites of involvement were vertebrae, pelvic bones and skull. Radiologically the osteolytic lesions were commonest. Bone lesions were associated with abdomino-pelvic disease in 3 patients. Cisplatinum based chemotherapy in addition to local radiation resulted in significant response in 2 patients; one complete and one partial response. The median survival was 7.5 months (range 6-39 months) after bone metastasis. We conclude bone involvement in cancer ovary is associated with poor prognosis.
.
'
Key words: cancer ovary, bone metastasis, radiotherapy, chemotherapy
Introduction Cancer ovary is the second commonest gynaecological malignancy seen among women. Epithelial histology is most frequent (8590%), followed by germ cell (5-6%), stromal (5%) and sex cord tumours. The disease spreads via transcoelomic, lymphatic and haematogenous route and may involve opposite ovary, fallopian tube, uterus, other pelvic organs, peritoneum, para aortic nodes, in-
testine, pleura and to liver in order of decreasing frequency.l) Metastasis to distant sites e.g. bones is very rare. An incidence of 0 4 % has been described in various clinical and autopsy studies.'-') Over last 3 years among 103 patients of cancer ovary we have seen 4 patients with bone metastasis.
Case Presentation
1. Mrs. SA, aged 40 presented in April
Received: Sep. 11,1991 Reprint request to: Dr. Lalit Kumar, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi 110029, India
L. M A R BT AL.
1990 with history of pain and distension of abdomen, loss of appetite of 8 months duration. On examination she had ascitis and hard irregular mass in pelvis. Evaluation for breast and gastro intestinal tract was normal. With diagnosis of ovarian malignancy she underwent laparotomy. On operation 6 Z of straw colour peritoneal fluid was drained; right ovary was enlarged - 1 5 ~10 cm size, irregular with variable consistency; left ovary was 10x 8 cm size and multilobulated. Omentum was adherent with the main tumour. Peritoneum was studied with multiple small (24 mm) seedlings. Uterus was normal, both tubes were distended with small seedlings. Liver was normal and para aortic nodes were not enlarged. Panhysterectomy (hysterectomy with bilateral salpingo-oophorectomy) with omentectomy was done. Histopathology revealed mucinous cyst adenocarcinoma of both ovaries and tubes with evidence of deposits in omentum. She was advised 6 cycles of combination chemotherapy (CP) using injection cisplatinum 50 mg/m2 IV day 1, injection cyclophosphamide 1 g/mz IV day 1 Q3 weeks. She received 3 courses irregularly till July 1990. Patient presented after a gap of 2 months with low back ache since 4 weeks. Examination revealed marked pallor and tenderness over lumber (L) 2-3 spine. InvestigationsHaemoglobin 3.4 g/dZ, WBC 3.3 x lOe/Z, platelets 48 x 109/Z. Peripheral smear was suggestive of normocytic normochromic anemia. Liver and renal functions-normal. Lumber spine X-ray showed collapse of Lz-r spine; pelvis X-ray alp view showed multiple lytic lesions in iliac bone and ischium, skull X-ray lateral view multiple osteo-lytic lesions. Bone marrow biopsy showed presence of metastatic epithelial tumour cells which were positive on mucicarmine stain. She received local radiotherapy to lumber spine (3,000 cGy in 10 fractions over 2 week) with partial pain relief. She was advised blood transfusions and analgesics. Patient expired at home one month later due to progressive disease. 2. Mrs. N, aged 35, was diagnosed to have papillary serous adenocarcinoma of ovary in July 1988. She had undergone debulking surgery for bilateral ovarian tumour with omen310
tectomy in a local hospital. Post operatively there was significant gross residual disease. She received 3 cycles of CFP chemotherapy (injection cisplatinum 30 mg/mz IV day 1 and 8, injection 5-flouro uracil 500 mg/mZ IV day 1 and 8 and tablet cyclophosphamide 100 mg/ mz orally day 1-14 Q4 weeks) following which she underwent panhysterectomy in September 1988 at this institute. For residual peritoneal deposits she received further chemotherapy and completed 6 cycles of CFP chemotherapy in July 1989. Re-evaluation laparotomy done in September 1989 confirmed complete response which was confirmed pathologically. She was on regular follow up till November 1990 when she presented with lump in abdomen and pain in left lower chest wall. Examination revealed-tender, ill defined bony swelling over left 7-9th ribs in anterior axillary line. Pelvic examination revealed-hard nodular mass at the vault. Investigationshaemoglobin 9.1 gm/dZ, WBC 6 . 7 lOg/Z, ~ platelets 549 x lO@/Z;liver and renal functions normal ; chest X-ray-destructive rib lesions in left 7-9th ribs. CAT scan of abdomen and pelvis revealed multiple para aortic lymph nodal masses with diffuse peritoneal spread of the disease. Fine needle aspiration cytology (FNAC) from the chest wall mass confirmed metastatic papillary adenocarcinoma. She received palliative local radiotherapy (800 cGy in single fraction)8) to chest wall lump. This was followed by palliative chemotherapy using injection cisplatinum 50 mg/mz IV day 1, injection cyclophosphamide 1 g/m2 IV day 1 Q3 weeks. She received 5 cycles of above chemotherapy with minimal response. Patient expired at home in September 1991 due to progressive disease. 3. Mrs. KD, aged 55 was diagnosed to have stage IIIC (FIGO) papillary serous cyst adenocarcinoma in September 1988 on the basis of laparotomy and histopathological findings. She presented 6 weeks later in October 1988 with complaints of pain and difficulty in walking. There was no history of trauma. Examination on admission revealed enlarged right inguinal lymph nodes, three 2 x 3 cm, hard and nontender; per abdomenenlarged liver 4 cm below costal margin, firm
BONE METASTASIS IN OVARIAN CANCER
and nontender. Investigations: blood-haemoglobin 11.1 Gm/dZ, WBC 9 x lOo/l, platelets 3 0 0 lOo/Z. ~ Serum bilirubin 0.6 mg%, serum alkaline phosphatase-24 KA (normal 3-13 KA), SGOT/SGPT-41/31 IU, serum proteins-total 7.2 g%, albumin 3.4 g% ; renal functions-normal. Ultrasonography and radionuclide scan of liver showed enlarged liver with multiple hypoechoic areas in left lobe of liver. FNAC of right inguinal lymph node revealed metastatic papillary adenocarcinoma, morphologically similar to primary in ovary. Pelvis X-ray alp view showed pathological fracture of left pubic symphysis and lytic lesions with sclerotic areas in inferior ramus of pubis. She received local radiotherapy (3,000 cGy in 10 fractions over 2 weeks) to pelvic bones with significant pain relief. Following this she received 6 cycles of CAP (cyclophosphamide 600 mg/mz IV day 1 adriamycin 30 mg/mz IV day 1, injection cisplatinum 50 mg/m2 IV day 1) ti11 June 1989. Repeat ultrasound showed significant regression of liver metastasis. Inguinal lymph nodes regressed completely. Pelvis X-ray showed evidence of sclerosis. Patient was subsequently lost to follow up. 4. Mrs. S, aged 25, presented in July 90 with acute colicky pain in right lower abdomen. She had undergone laparotomy in a local hospital and was found to have twisted right ovarian tumour of 20x 15x 12 cm size. Tumour appeared solid with areas of haemorrhages and necrosis. Left ovary, tube, uterus and liver were normal with no evidence of peritoneal deposits or para aortic lymph nodes enlargement. She did not receive any post operative treatment. Patient presented to this Institute in October 1990 with low back ache of 3 weeks duration. Examination revealed tenderness over Lumber 2-5 spine. Rest of the systemic examination was within normal limits. Investigations: blood-haemoglobin 14.1 g/dl, WBC 4 . 2 109/1, ~ platelets 120x loe/ I ; liver and renal functions-normal; lumber spine X-ray (alp and lateral view) showed destruction of La-L, spine. CAT scan abdomen and pelvis showed enlarged upper para aortic and interaortic lymph nodes with destructive lesions in lumber 3-5 spine. The
99 m technitium bone scan revealed increased radionuclide uptake in La-Lj vertebrae. Serum B HCG and serum a feto protein were negative. Histopathological review of right ovarian specimen revealed features of mixed germ cell tumour showing areas of dysgerminoma and foci of embryonal cell carcinoma. She received PVB chemotherapy (injection cisplatinum 20 mg/mz IV dl-5, injection bleomycin 15 mg/mz IV dl, 8, 15, injection vinblastine 6 mg/mz IV dl-2Q 3 weeks) along with local radiotherapy to lumber spine. She received 3,000 cGy; 300 cGy/day in 10 fractions over 2 weeks. She completed 4 courses of PVB chemotherapy till January 1991. During chemotherapy she had episodes of severe myelosuppression and fever which improved after antibiotics. Repeat CAT scan abdomen and pelvis in January 1991 revealed complete regression of para aortic lymph nodes with evidence of sclerosis in b-L5 vertebral lesion. Patient relapsed in June 1991 when presented with gross retroperitoneal mass. Laparotomy revealed wide spread intra abdominal disease with liver involvement. She expired at home due to progressive disease in August 1991.
Discussion Bone metastasis in carcinoma ovary is rare. An incidence of 0 4 % have been reported in clinical and autopsy studies.1-8) Bergman" and Dauplat et aL2) reported an incidence 2 cm) No Persistent disease Bone marrow
9. Symptoms
Low backache
6. Second look Sx 7. Abdominal status
10. Time since primary diagnosis (MO) 11. Sites of bone metastasis 12. 13. 14. 15.
Treatment Outcome Overall survival (MO) Survival after diagnosis (MO) of bone metastasis
5 Skull, lumbar spine, pelvis RT+CP Died 6 3
Serous papillary IIIC Debulking sx Gross (>2 cm) Yes Recurrence
Swelling chest wall 31 Ribs RT+CP Died 39 11
Serous papillary IIIC PH
Mixed GCT IA Left SPO
Gross (>2 cm) No Recurrence
Nil No
-
Inguinal lymph node Low Difficulty backache in walking 1.5 6 Pelvic bones Lumber spine RT+PVB RT+CAP Lost to FU Died 10 14 4 11
PH : pan hysterectomy ; Sx : surgery ; SPO : salpingo oophorectomy ; CAP : cisplatinurn, adriamycin, cyclophosphamide; CP :cisplatinum, cyclophosphamide; PVB :cisplatinum, bleomycin, vinblastine ;GCT : germ cell tumour ; MO : months ; FU : follow up
commonly there may be partial or complete collapse of spine as seen in case 1 and 4 here. Osteosclerotic (as seen in case 3) or mixed lytic/sclerotic lesions may also occur. Mettler et al. (1982) studied the role of bone scan imaging in 43 asymptomatic patients for early detection of bone metastasis. Innone of these, bone scan was abnormal. The occurrence of bone lesions in a diagnosed case of cancer ovary is usually due to disease. However other possibilities e.g. infection, infarction, unrelated second neoplasm should also be kept in mind. Bone lesions here in 4 patients developed within 1.5-31 months of primary diagnosis. These observations are similar to earlier studies.214) Further bone lesions usually develop in advanced stage of disease. I n Mettlers'e) series among 4 patients with bone metastasis-3 had stage I11 disease while one had stage I disease. I n another report of 7 patient& had stage 111, one stage IV and 2 patients had stage I1 disease.') I n 312
present study 2 patients had stage IIIC and one had stage IV disease. One patient with mixed germ cell tumour had stage I disease on initial presentation. Histopathologicallyserous, and mucinous cyst adenocarcinoma are common subtypes affected, as seen here also (serous-2, mucinous-1). Uncommonly bone metastasis may occur in germ cell tumours-dysgerminoma, teratoma etc. Norris et aZ.9) in a study (from Armed Forces institute of pathology) of 58 patients with immature teratomas found 2 cases with bone metastasis. McDougall et d.6)have described a case of struma ovarii presenting as paraparesis from dorsal spine metastasis. They also reviewed 5 earlier cases of struma ovarii with bone metastasis. Presence of abdomino-pelvic disease in case 1-3 and review of literature suggests that bone metastasis rarely occurs alone and control of the primary disease still remains a major problem. Further poor reeponse to chemo-
BONE MBTASTASIS IN OVARIAN CANCER
therapy in case 1 and 2 may be suggestive of chemotherapy resistance. On contrary-germ cell tumours are highly chemosensitive as suggested here in case 4 by achievement of complete response even in stage IV disease. Pancytopenia in case 1 could be explained due to bone marrow involvement. Bone marrow metastasis has rarely been described earlier.10-12) Here localised radiotherapy could improve the symptoms markedly in all patients suggest that this should be used in addition to systemic chemotherapy. Cisplatinum based combination chemotherapy is generally effective. However, once the bone metastasis occurs, survival is generally poor. Dauplat et aL2) have reported a median survival of 4 months (range 1-7 months). Clain et d.8) observed a median survival of 9 months in a series of 11 patients. The median survival of 7.5 months (range 3-11 months) in our study is similar to these observations. Our experience and review of literature suggests that once the bone metastasis develop the course is rapidly progressive resulting in clinical deterioration and short survival. Therefore patients of ovarian carcinoma with abrupt onset of severe localised pain should be promptly investigated using radiological and/or bone scan and tumour markers studies. Biopsy from bone lesions must be obtained for histopathologic and culture studies. Local radiation is effective in relieving the pain, therefore should be used in addition to cisplatin based combination chemotherapy.
11.
References
12.
1. Bergman F. Carcinoma of ovary: A clinical
2.
3.
4.
5.
6.
10.
and pathological study of 86 autopsied cases with special reference to mode of spread. Acta Obstet GynaecolScand 1966; 45 : 211-231 Dauplat J, Hacker NF, Nieberg RK, Berek JS, Rose TP,Sagae S. Distant metastases in epithelial ovarian carcinoma. Cancer 1987; 60: 1561-1 566 Clain A. Secondary malignant disease of bone. Br J Cancer 1965; 19 : 15-19 Abdul Karim FW,Kida M, Wentz WB, Carter JR, Sorenson KS, Macfee M, Zika J, Makey JT. Bone metastases from gynaecological carcinomas-a clincopathologicalstudy. Gyanaecol Oncoll990; 39 : 108-114 McDougall IR, Krasne D, Hanbery JW, Collins, JA. Metastatic struma ovarii presenting as paraparesis from a spinal metastasis. J NwZ Med 1989; 30: 407411 Mettler FA Jr, Christie JH, Crow NE Jr, Gracia JF, Wicks JD, Barton SA. Radio nuclide bone scan, radiographic bone survey, and aenaline phosphatase studies of limited value in asymptomatic patients with ovarian carcinoma. Cuncer 1982; 50 :1483-1485 Brufman G, Kraskokuki D, Biram S. Metastatic bone involvement in gynaecological malignancies. Radio Clin 1978; 47 :456-463 Vargha Z, Glicksman A, Boland J. Single dose radiation therapy in the palliation of metastatic disease. Am JRadioll969; 93 : 1181-1184 Norris HJ, Zirkin HJ, Benson WL. Immature (malignant) teratoma of the ovary: A clinical and pathological study of 58 cases. Cancer 1976; 37: 2359-2372 Julian CJ, Goss T, Blanchard K, Woodruff D. Biological behaviour of primary ovarian malignancy. Obstet oyMecoll974; 44 : 873-884 Blythe JG, Buchsbaum H. Bone marrow biopsies in patients with gynaewlogical malignancies. GyMecol Oncol1977; 5: 40-42 Bradof JE,Hakes TB, Ochoa M, Golbey R. Germ cell malignancies of the ovary. Cuncer 1982; 50 : 1072-1075
313
Bone Metastasis in Ovarian Cancer
Lalit Kumar,') V. L. Bhargava?) R. C. Keshav Rao,s) G. K. Rath,') and S. P. Kataria') 1 ) Department of Medical Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences,
New Delhi, India 2) Department of Gynaecology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New
Delhi, India 3) Department of Radiodiagnoris, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences,
New Delhi, India 4 ) Department of Radiotherapy, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, N m Delhi, India
Abstract Bone involvement in carcinoma of ovary occurs rarely. In a review of 103 patients over last 3 years we have seen 4 such patients (serous-2, mucinous-1, mixed germ cell tumour-1). Patients presented with severe localized bone pain, bony swelling and difficulty in walking. The common sites of involvement were vertebrae, pelvic bones and skull. Radiologically the osteolytic lesions were commonest. Bone lesions were associated with abdomino-pelvic disease in 3 patients. Cisplatinum based chemotherapy in addition to local radiation resulted in significant response in 2 patients; one complete and one partial response. The median survival was 7.5 months (range 6-39 months) after bone metastasis. We conclude bone involvement in cancer ovary is associated with poor prognosis.
.
'
Key words: cancer ovary, bone metastasis, radiotherapy, chemotherapy
Introduction Cancer ovary is the second commonest gynaecological malignancy seen among women. Epithelial histology is most frequent (8590%), followed by germ cell (5-6%), stromal (5%) and sex cord tumours. The disease spreads via transcoelomic, lymphatic and haematogenous route and may involve opposite ovary, fallopian tube, uterus, other pelvic organs, peritoneum, para aortic nodes, in-
testine, pleura and to liver in order of decreasing frequency.l) Metastasis to distant sites e.g. bones is very rare. An incidence of 0 4 % has been described in various clinical and autopsy studies.'-') Over last 3 years among 103 patients of cancer ovary we have seen 4 patients with bone metastasis.
Case Presentation
1. Mrs. SA, aged 40 presented in April
Received: Sep. 11,1991 Reprint request to: Dr. Lalit Kumar, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi 110029, India
L. M A R BT AL.
1990 with history of pain and distension of abdomen, loss of appetite of 8 months duration. On examination she had ascitis and hard irregular mass in pelvis. Evaluation for breast and gastro intestinal tract was normal. With diagnosis of ovarian malignancy she underwent laparotomy. On operation 6 Z of straw colour peritoneal fluid was drained; right ovary was enlarged - 1 5 ~10 cm size, irregular with variable consistency; left ovary was 10x 8 cm size and multilobulated. Omentum was adherent with the main tumour. Peritoneum was studied with multiple small (24 mm) seedlings. Uterus was normal, both tubes were distended with small seedlings. Liver was normal and para aortic nodes were not enlarged. Panhysterectomy (hysterectomy with bilateral salpingo-oophorectomy) with omentectomy was done. Histopathology revealed mucinous cyst adenocarcinoma of both ovaries and tubes with evidence of deposits in omentum. She was advised 6 cycles of combination chemotherapy (CP) using injection cisplatinum 50 mg/m2 IV day 1, injection cyclophosphamide 1 g/mz IV day 1 Q3 weeks. She received 3 courses irregularly till July 1990. Patient presented after a gap of 2 months with low back ache since 4 weeks. Examination revealed marked pallor and tenderness over lumber (L) 2-3 spine. InvestigationsHaemoglobin 3.4 g/dZ, WBC 3.3 x lOe/Z, platelets 48 x 109/Z. Peripheral smear was suggestive of normocytic normochromic anemia. Liver and renal functions-normal. Lumber spine X-ray showed collapse of Lz-r spine; pelvis X-ray alp view showed multiple lytic lesions in iliac bone and ischium, skull X-ray lateral view multiple osteo-lytic lesions. Bone marrow biopsy showed presence of metastatic epithelial tumour cells which were positive on mucicarmine stain. She received local radiotherapy to lumber spine (3,000 cGy in 10 fractions over 2 week) with partial pain relief. She was advised blood transfusions and analgesics. Patient expired at home one month later due to progressive disease. 2. Mrs. N, aged 35, was diagnosed to have papillary serous adenocarcinoma of ovary in July 1988. She had undergone debulking surgery for bilateral ovarian tumour with omen310
tectomy in a local hospital. Post operatively there was significant gross residual disease. She received 3 cycles of CFP chemotherapy (injection cisplatinum 30 mg/mz IV day 1 and 8, injection 5-flouro uracil 500 mg/mZ IV day 1 and 8 and tablet cyclophosphamide 100 mg/ mz orally day 1-14 Q4 weeks) following which she underwent panhysterectomy in September 1988 at this institute. For residual peritoneal deposits she received further chemotherapy and completed 6 cycles of CFP chemotherapy in July 1989. Re-evaluation laparotomy done in September 1989 confirmed complete response which was confirmed pathologically. She was on regular follow up till November 1990 when she presented with lump in abdomen and pain in left lower chest wall. Examination revealed-tender, ill defined bony swelling over left 7-9th ribs in anterior axillary line. Pelvic examination revealed-hard nodular mass at the vault. Investigationshaemoglobin 9.1 gm/dZ, WBC 6 . 7 lOg/Z, ~ platelets 549 x lO@/Z;liver and renal functions normal ; chest X-ray-destructive rib lesions in left 7-9th ribs. CAT scan of abdomen and pelvis revealed multiple para aortic lymph nodal masses with diffuse peritoneal spread of the disease. Fine needle aspiration cytology (FNAC) from the chest wall mass confirmed metastatic papillary adenocarcinoma. She received palliative local radiotherapy (800 cGy in single fraction)8) to chest wall lump. This was followed by palliative chemotherapy using injection cisplatinum 50 mg/mz IV day 1, injection cyclophosphamide 1 g/m2 IV day 1 Q3 weeks. She received 5 cycles of above chemotherapy with minimal response. Patient expired at home in September 1991 due to progressive disease. 3. Mrs. KD, aged 55 was diagnosed to have stage IIIC (FIGO) papillary serous cyst adenocarcinoma in September 1988 on the basis of laparotomy and histopathological findings. She presented 6 weeks later in October 1988 with complaints of pain and difficulty in walking. There was no history of trauma. Examination on admission revealed enlarged right inguinal lymph nodes, three 2 x 3 cm, hard and nontender; per abdomenenlarged liver 4 cm below costal margin, firm
BONE METASTASIS IN OVARIAN CANCER
and nontender. Investigations: blood-haemoglobin 11.1 Gm/dZ, WBC 9 x lOo/l, platelets 3 0 0 lOo/Z. ~ Serum bilirubin 0.6 mg%, serum alkaline phosphatase-24 KA (normal 3-13 KA), SGOT/SGPT-41/31 IU, serum proteins-total 7.2 g%, albumin 3.4 g% ; renal functions-normal. Ultrasonography and radionuclide scan of liver showed enlarged liver with multiple hypoechoic areas in left lobe of liver. FNAC of right inguinal lymph node revealed metastatic papillary adenocarcinoma, morphologically similar to primary in ovary. Pelvis X-ray alp view showed pathological fracture of left pubic symphysis and lytic lesions with sclerotic areas in inferior ramus of pubis. She received local radiotherapy (3,000 cGy in 10 fractions over 2 weeks) to pelvic bones with significant pain relief. Following this she received 6 cycles of CAP (cyclophosphamide 600 mg/mz IV day 1 adriamycin 30 mg/mz IV day 1, injection cisplatinum 50 mg/m2 IV day 1) ti11 June 1989. Repeat ultrasound showed significant regression of liver metastasis. Inguinal lymph nodes regressed completely. Pelvis X-ray showed evidence of sclerosis. Patient was subsequently lost to follow up. 4. Mrs. S, aged 25, presented in July 90 with acute colicky pain in right lower abdomen. She had undergone laparotomy in a local hospital and was found to have twisted right ovarian tumour of 20x 15x 12 cm size. Tumour appeared solid with areas of haemorrhages and necrosis. Left ovary, tube, uterus and liver were normal with no evidence of peritoneal deposits or para aortic lymph nodes enlargement. She did not receive any post operative treatment. Patient presented to this Institute in October 1990 with low back ache of 3 weeks duration. Examination revealed tenderness over Lumber 2-5 spine. Rest of the systemic examination was within normal limits. Investigations: blood-haemoglobin 14.1 g/dl, WBC 4 . 2 109/1, ~ platelets 120x loe/ I ; liver and renal functions-normal; lumber spine X-ray (alp and lateral view) showed destruction of La-L, spine. CAT scan abdomen and pelvis showed enlarged upper para aortic and interaortic lymph nodes with destructive lesions in lumber 3-5 spine. The
99 m technitium bone scan revealed increased radionuclide uptake in La-Lj vertebrae. Serum B HCG and serum a feto protein were negative. Histopathological review of right ovarian specimen revealed features of mixed germ cell tumour showing areas of dysgerminoma and foci of embryonal cell carcinoma. She received PVB chemotherapy (injection cisplatinum 20 mg/mz IV dl-5, injection bleomycin 15 mg/mz IV dl, 8, 15, injection vinblastine 6 mg/mz IV dl-2Q 3 weeks) along with local radiotherapy to lumber spine. She received 3,000 cGy; 300 cGy/day in 10 fractions over 2 weeks. She completed 4 courses of PVB chemotherapy till January 1991. During chemotherapy she had episodes of severe myelosuppression and fever which improved after antibiotics. Repeat CAT scan abdomen and pelvis in January 1991 revealed complete regression of para aortic lymph nodes with evidence of sclerosis in b-L5 vertebral lesion. Patient relapsed in June 1991 when presented with gross retroperitoneal mass. Laparotomy revealed wide spread intra abdominal disease with liver involvement. She expired at home due to progressive disease in August 1991.
Discussion Bone metastasis in carcinoma ovary is rare. An incidence of 0 4 % have been reported in clinical and autopsy studies.1-8) Bergman" and Dauplat et aL2) reported an incidence 2 cm) No Persistent disease Bone marrow
9. Symptoms
Low backache
6. Second look Sx 7. Abdominal status
10. Time since primary diagnosis (MO) 11. Sites of bone metastasis 12. 13. 14. 15.
Treatment Outcome Overall survival (MO) Survival after diagnosis (MO) of bone metastasis
5 Skull, lumbar spine, pelvis RT+CP Died 6 3
Serous papillary IIIC Debulking sx Gross (>2 cm) Yes Recurrence
Swelling chest wall 31 Ribs RT+CP Died 39 11
Serous papillary IIIC PH
Mixed GCT IA Left SPO
Gross (>2 cm) No Recurrence
Nil No
-
Inguinal lymph node Low Difficulty backache in walking 1.5 6 Pelvic bones Lumber spine RT+PVB RT+CAP Lost to FU Died 10 14 4 11
PH : pan hysterectomy ; Sx : surgery ; SPO : salpingo oophorectomy ; CAP : cisplatinurn, adriamycin, cyclophosphamide; CP :cisplatinum, cyclophosphamide; PVB :cisplatinum, bleomycin, vinblastine ;GCT : germ cell tumour ; MO : months ; FU : follow up
commonly there may be partial or complete collapse of spine as seen in case 1 and 4 here. Osteosclerotic (as seen in case 3) or mixed lytic/sclerotic lesions may also occur. Mettler et al. (1982) studied the role of bone scan imaging in 43 asymptomatic patients for early detection of bone metastasis. Innone of these, bone scan was abnormal. The occurrence of bone lesions in a diagnosed case of cancer ovary is usually due to disease. However other possibilities e.g. infection, infarction, unrelated second neoplasm should also be kept in mind. Bone lesions here in 4 patients developed within 1.5-31 months of primary diagnosis. These observations are similar to earlier studies.214) Further bone lesions usually develop in advanced stage of disease. I n Mettlers'e) series among 4 patients with bone metastasis-3 had stage I11 disease while one had stage I disease. I n another report of 7 patient& had stage 111, one stage IV and 2 patients had stage I1 disease.') I n 312
present study 2 patients had stage IIIC and one had stage IV disease. One patient with mixed germ cell tumour had stage I disease on initial presentation. Histopathologicallyserous, and mucinous cyst adenocarcinoma are common subtypes affected, as seen here also (serous-2, mucinous-1). Uncommonly bone metastasis may occur in germ cell tumours-dysgerminoma, teratoma etc. Norris et aZ.9) in a study (from Armed Forces institute of pathology) of 58 patients with immature teratomas found 2 cases with bone metastasis. McDougall et d.6)have described a case of struma ovarii presenting as paraparesis from dorsal spine metastasis. They also reviewed 5 earlier cases of struma ovarii with bone metastasis. Presence of abdomino-pelvic disease in case 1-3 and review of literature suggests that bone metastasis rarely occurs alone and control of the primary disease still remains a major problem. Further poor reeponse to chemo-
BONE MBTASTASIS IN OVARIAN CANCER
therapy in case 1 and 2 may be suggestive of chemotherapy resistance. On contrary-germ cell tumours are highly chemosensitive as suggested here in case 4 by achievement of complete response even in stage IV disease. Pancytopenia in case 1 could be explained due to bone marrow involvement. Bone marrow metastasis has rarely been described earlier.10-12) Here localised radiotherapy could improve the symptoms markedly in all patients suggest that this should be used in addition to systemic chemotherapy. Cisplatinum based combination chemotherapy is generally effective. However, once the bone metastasis occurs, survival is generally poor. Dauplat et aL2) have reported a median survival of 4 months (range 1-7 months). Clain et d.8) observed a median survival of 9 months in a series of 11 patients. The median survival of 7.5 months (range 3-11 months) in our study is similar to these observations. Our experience and review of literature suggests that once the bone metastasis develop the course is rapidly progressive resulting in clinical deterioration and short survival. Therefore patients of ovarian carcinoma with abrupt onset of severe localised pain should be promptly investigated using radiological and/or bone scan and tumour markers studies. Biopsy from bone lesions must be obtained for histopathologic and culture studies. Local radiation is effective in relieving the pain, therefore should be used in addition to cisplatin based combination chemotherapy.
11.
References
12.
1. Bergman F. Carcinoma of ovary: A clinical
2.
3.
4.
5.
6.
10.
and pathological study of 86 autopsied cases with special reference to mode of spread. Acta Obstet GynaecolScand 1966; 45 : 211-231 Dauplat J, Hacker NF, Nieberg RK, Berek JS, Rose TP,Sagae S. Distant metastases in epithelial ovarian carcinoma. Cancer 1987; 60: 1561-1 566 Clain A. Secondary malignant disease of bone. Br J Cancer 1965; 19 : 15-19 Abdul Karim FW,Kida M, Wentz WB, Carter JR, Sorenson KS, Macfee M, Zika J, Makey JT. Bone metastases from gynaecological carcinomas-a clincopathologicalstudy. Gyanaecol Oncoll990; 39 : 108-114 McDougall IR, Krasne D, Hanbery JW, Collins, JA. Metastatic struma ovarii presenting as paraparesis from a spinal metastasis. J NwZ Med 1989; 30: 407411 Mettler FA Jr, Christie JH, Crow NE Jr, Gracia JF, Wicks JD, Barton SA. Radio nuclide bone scan, radiographic bone survey, and aenaline phosphatase studies of limited value in asymptomatic patients with ovarian carcinoma. Cuncer 1982; 50 :1483-1485 Brufman G, Kraskokuki D, Biram S. Metastatic bone involvement in gynaecological malignancies. Radio Clin 1978; 47 :456-463 Vargha Z, Glicksman A, Boland J. Single dose radiation therapy in the palliation of metastatic disease. Am JRadioll969; 93 : 1181-1184 Norris HJ, Zirkin HJ, Benson WL. Immature (malignant) teratoma of the ovary: A clinical and pathological study of 58 cases. Cancer 1976; 37: 2359-2372 Julian CJ, Goss T, Blanchard K, Woodruff D. Biological behaviour of primary ovarian malignancy. Obstet oyMecoll974; 44 : 873-884 Blythe JG, Buchsbaum H. Bone marrow biopsies in patients with gynaewlogical malignancies. GyMecol Oncol1977; 5: 40-42 Bradof JE,Hakes TB, Ochoa M, Golbey R. Germ cell malignancies of the ovary. Cuncer 1982; 50 : 1072-1075
313
