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Hemolytic anemia associated with an ovarian tumor
Hemolytic Anemia Associated with an Ovarian Tumor
M. ALLEN DAWSON, M.D. WILIMER TALBERT, M.D. JOHN W. YARBRO, M.D.* Lexington, Kentucky
A case of hemolytic anemia secondary to an ovarian tumor is reported. Recognition of this rare cause of hemolytic anemia is important because treatment with corticosteroids and splenectomy has been ineffectual, whereas tumor excision is almost always curative. Our case is unusual in that it is the first thecagranulosa cell tumor .of the ovary found in association with hemolytic anemia; almost all the previous cases were teratomas or adenocarcinomas. Possible mechanisms of the hemolytic anemia are discussed. Hemolytic anemia caused by ovarian tumors has been recognized since the report of West-Watson and Young in 1938 [l]. Although rare, diagnosis is important because excision of the ovarian tumor is almost invariably followed by complete remission of the hemolytic process. Our case represents the twenty-fourth reported case of hemolytic anemia associated with an ovarian tumor -and the fivrst case associated with a probable theta-granulosa type of tumor. CASE REPORT
From the Departments of Medicine and Pathology, University of Kentucky Medical Center, Lexington, Kentucky 40506. Requests for reprints should be addressed to Dr. John W. Yarbro. Manuscript received March 6, 1970. * Present address: American Oncologic Hospital, Philadelphia, Pennsylvania 19111.
552
A forty-one year old white woman (A. O., UKMC No. 10-69-186) was admitted to the University of Kentucky Hospital on September 9, 1968, with complaints of weakness, exertional dyspnea and easy fatigue. She had had no menses for four months except for spotting on one occasion. She had not had abdominal or pelvic pain, fever or jaundice. On physical examination, the oral temperature was 98.6’F, pulse rate 80/minute, respirations 18/minute and blood pressure 144/68 mm Hg. The patient was pale but not acutely ill. There was no icterus or lymphadenopathy. The lungs were clear. The heart was normal except for a vibratory systolic murmur audible over the entire precordium. The liver edge wa’s felt 8 cm below the right costal margin and the spleen 20 cm below the left costal margin. Pelvic examination was normal. The hematocrit was 13 per cent, the hemoglobin 3.8 gm per cent, the white blood count 1,5OO/cu mm, and the platelet count 162,000/ cu mm. The white blood cell differential count showed 56 per cent segmented neutrophils, 32 per cent band forms, 2 per cent metamyelocytes, 6 per cent lymphocytes and 4 per cent monocytes. The peripheral smear showed marked poikilocytosls and 2 nucleated red blood cells were seen/ 100 white blood cells counted. The reticulocyte count was 4,2 per cent. The serum total bllirubin was 0.9 mg per cent. The Coombs test vias negative. The Cr51 red cell survival determlna-
The Amorlc~n
Journal
of Mdlclne
H~OLYTI~
ANEMIA AND OVARIAN TUMOR -
DAWSON ET AL.
tion
showed a half-life of thirteen days, Bone marrow could not be obtained by aspiration from the sternum. A bone marrow biopsy specimen was then obtained from the iliac crest, using a Vim-Silverman needle. This revealed a slight increase in the marrow fibrous tissue and wa’s compatible with myelofibrosis. The patient was given a transfusion of 6 units of packed red blood cells and her condition improved. Corticosteroids were not administered. On discharge from the hospital the hematocrit was 32 per cent. Two months later the hematocrit was 15 per cent and the hemoglobin 6.0 gm per cent; the patient was readmitted to the hospital for splenectomy. A bone marrow biopsy specimen taken from the’ iliac crest revealed hyperplasia of all cell lines with a slight in-. crease in the marrow fibrous tissue. It was thought at this time that she had a myeloproliferative disorder which was not myelofibrosis. At Iaparotomy, the spleen was massively enlarged and was removed. At this point a mass in the right ovary was discovered and excised. The left adrenal gland was abnormal and was removed. Pathologic examination revealed an ovarian tumor that measured 5.5 by 7.5 by 9.5 cm and weighed, 269 gm. The surface of the mass was quite vascular (Figure 1) and the cut surface was soft and yellow-orange. Despite multiple attemps to demonstrate viable tumor tissue, none could be found: the tumor was completely necrotic. However, reticulum stains of the tumor revealed a definite pattern (Figure 2) similar to that found in theta-granulosa cell tumors. The spleen weighed 1600 gm. Innumerable angiomas measuring 3 to 30 mm were present throughout the spleen. (Figures 3, 4, and 5.) On microscopic examination both the liver and spleen contained numerous megakaryocytes in the sinusoidal spaces. The left adrenal gland weighed 22 gm and contained a single nonencapsulated but well circumscribed cortical adenoma. At the time of operation the patient received 8 units of whole blood, after which the hematocrit was 32 per cent and the hemoglobin 9.6 gm per cent. Subsequently, she did not require any further transfusions. The platelet count was elevated, and on several occasions the white blood cell count was moderately elevated. A third bone marrow specimen, obtained from the sternum three months postoperatively, was entirely normal. On July 11, 1969, the patient returned to the hospital because of persistent menorrhagia; she underwent a total hysterectomy. This revealed a uterus weighing 160 gm with extensive adenomyosis. There was a corpus luteum cyst in remaining ovary.
Figure 1. Ovarian tumor with attached and prominent surface vasculature.
Figure
2.
Reticulum
stain
of ovarian
fallopian
tumor
tube
specimen
showing islands of necrotic epithelial cells separated by reticulum-rich fibrous septums. Original magnification x65.
COMMENTS West-Watson
and
ciation
of
Their
patient
whom
Young
hemolytic
,was a forty-four
hemolytic
Volume 50, April
[l]
anemia
1971
anemia
first and year
persisted
noted
the
ovarian old after
assotumor.
woman
in
splenec-
Horizontal section Figure 3. with transmitted light, showing stained. Natural size.
of spleen photographed numerous angiomas. Un-
553
HEMOLYTIC
ANEMIA
AND OVARIAN
TUMOR -
DAWSON
ET AL.
Figure 4. Sinusoidal character of the larger splenic angiomas. Fibrous thickening of the vascular septoms can be seen also. Original magnification x65.
tomy. During a repeat laparotomy in search of an accessory spleen an ovarian teratoma was found and removed after which an immediate and complete remission of the hemolytic anemia occurred. Subsequently, similar cases have been described [2-221 which, including our case, now total twentyfour in the world literature (Table I). Sixteen of the twenty-four ovarian tumors (67 per cent) were teratomas, and of these thirteen were dermoid cysts. Of the remaining eight patients, three had “ovarian cysts,” not further described; four had carcinomas: adenocarcinoma, pseudomucinous cystadenocarcinoma, papillary adenocarcinoma and anaplastic carcinoma; and our patient had a completely necrotic tumor which probably was a theta-granulosa cell tumor. In eleven cases [8-10,12,14,16-211 treatment
Figure 5. Compression of splenic substance by a small angioma. Follicular hyperplasia is not present. Original magnification x65.
554
of the hemolytic anemia was initiated with cot-ticosteroids, which resulted tin transient and slight improvement in the anemia in only four cases [10,17,18,20]. Six patients [1,3,5,10,12,16] underwent splenectomy prior to excision of the ovarian tumor. In two patients [3,10], a temporary remission followed, In all but two of the twenty-four cases the ovarian tumors were removed, which was followed by a complete and usually prompt remission of the hemolytic process except for one patient [5],who died at laparotomy and two patients [18,22] who had widespread metastatic disease from papillary adenocarcinoma. Thus, it is clear that appropriate treatment_ of the hemolytic anemia associated with an ovarian tumor is tumor removal; there seems to be no place for the use of corticosteroids or splenectomy, except in the presence of metastatic disease. Many features ‘in our patient were suggestive of a myeloproliferative disorder. Bone marrow biopsy was interpreted initially as showing an early increase in fibrous tissue, although in retrospect it is probable that it represented a poor biopsy specimen. A subsequent bone marrow biopsy specimen and aspirate showed hyperplasia or normal cellularity. The findings of small foci of megakaryocytes in the splenic sinusoids and liver also are consistent with a myeloproliferative disorder anbd remain unexplained. Finally, postoperative mild leukocytosis and thrombocytosis are in keeping with a myeloproliferative syndrome, although both could be secondary to splenectomy alone. The cause of hemolytic anemia associated with ovarian tumors remains unknown. It has been speculated [23-251 that tumor cells and erythrocytes may share antigens, with development of an autoimmune process. Thmis is indirectly supported by the finding of positive Coombs’ tests in fifteen of the twenty-three cases, although Dacie [26] has emphasized that there is no absolute evidence for an autoimmune process. Landaw [25] has called attention to the fact that in patients with hemolytic anemia secondary to carcinoma, the tumor usually has been an adenocarcinoma, which is a mucinproducing tumor. Possibly the mucin material is antigenic and leads to the development of antibodies which cross react with erythrocytes. In the cases of hemolytic anemia with ovarian tumors th’is speculation is probably more applicable [26] since, in addition to teratomata, adenocarcinomas and other cystic tumors have been found, all of which produce mucin. Hemolytic anemia has also been found in association with a dermoid tumor attached to the hilum of the spleen [26], and in
The American
Journal
of Medicine
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... ... ... .I.
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.
.
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?
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No response ...
Partial Partial
...
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... ...
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No response
No response No response Short remission ...
... ... ...
... ...
... ... ... ...
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Cr61 Half-life
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+
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?
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0 ?
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... +
+ +
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locytes Coombs
(pm %)
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with Ovarian
globin
Associated
Hemo-
Anemia
+ 0 ?
+ + +
+ +
+ ?
+ ?
+ +
Tumor
pable
+ +
megaly
Spleno-
Reported Cases of Hemolytic
Age (yr)
I
Case No.
TABLE
(At time of tumor excision)
(At time of tumor excision) ?
...
...
No effect
...
Short remission ... No effect
... ... ..I ...
No effect
(At time of tumor excision) Short remission ...
No effect
Splenectomy
response Remission
Partial
Remission
Remission
Remission Remission Remission Partial response
Remission Remission Remission
Died at operation Remission Died of transfusion Remission Remission Remission Remission Remission
Remission Slow response
Remission Remission
Tumor Excision
Theta-granulosa
Adenocarcinoma
Teratoma “Cysts” “Cystic degeneration” Dermoid Dermoid Dermoid Papillary adenocarcinoma Dermoid Anaplastic carcinoma Dermoid
Dermoid Pseudomucinous cystadenocarcinema Dermoid Dermoid Dermoid Dermoid Dermoid Dermoid Tetaroma Dermoid
Teratoma “Cyst”
Histologic Diagnosis
HEMOLYTIC
ANEMIA
AND OVARIAN TUMOR -
DAWSON
ET AL.
another case was found to be secondary to a mesenteric cyst which did not originate in the ovary [28]. The patient described by Burkert et al. [22] was shown to have a hemolytic serum factor; when normal red cells were incubated with this patient’s serum for one hour, the autohemolysis test showed 14.5 per cent hemolysis (control 3.0 per cent). There is evidence from animal experiments [29,30] that the injection of necrotic material from tumor extracts into normal animals produces both a shortening of the erythrocyte half-life and hyperactivity of the reticuloendothelial system.
One final point raised by our case concerns the relationship of the splenic angiomas to the hemolytic anemia and their relationship to the ovarian tumor. Data on the spleen in the recorded cases of hemolytic anemia and ovarian tumor are usually limited to the weight of the organ. Splenic angiomas were not described in the reports reviewed. Angiomas could easily have gone undetected if few in number and small. Their relationship to the syndrcme is not clear. Whether they represent a response to products of the tumor or are involved in the mechanism of the hemolysis remains to be elucidated.
REFERENCES 1.
2.
3. 4.
5. 6.
7.
8.
9.
10.
11.
12.
13.
14.
15. 16.
556
West-Watson WN, Young CJ: Failed splenectomy in acholuric jaundice and the relation of toxaemia to the haemolytic crises. Brit Med J 1: 1305, 1938. Watson CJ: Hemolytic jaundice and macrocytic hemolytic anemia. Certain observations in a series of 35 cases. Ann Intern Med 12: 1782, 1939. Singer K, Dameshek W: Symptomatic hemolytic anemia. Ann Intern Med 15: 544, 1941. Jones E, Tillman C: A case of hemolytic anemia relieved by remova,l of an ovarian tumor. JAMA 128: 1225, 1945. Lindeboom GA: Rare forms of symptomatic hemolytic anemia. Acta Haemat 4: 343, 1950. Allibone EC, Collins DH: Symptomatic haemolytic anaemia associated with ovarian teratoma in a child. J Clin Path 4: 412, 1951. de Gruchy GC: The diagnosis and management of acquired haemolytic anaemia. Aust Ann Med 3: 106, 1954. Wuhrmann F: Einige aktuelle klinische Probleme aus der Humoralpathologie. Bull Schweiz Akad Med Wiss 10: 180, 1954. Andre R, Dreyfus B, Salmon C: Anemie hemolytique et kyste dermoide de I’ovaire. Bull Sot Hop Paris 71: 1062, 1955. Prochatka J: Symptomaticka hemolyticka chudokrevnost pri dermoidni cyste Vajecniku. Vnitrni Lek 2: 240, 1956. Barry KG, Crosby WH: Autoimmune hemolytic anemia arrested by removal of an ovarian teratoma. Review of the literature and report of a case. Ann Intern Med 47: 1002, 1957. Muller W, Schubothe H, Elert R: Die hlmolytische Anlmie als Begleiterkrankung bei Dermoidzysten. Geburtsh Frauenheilk 18: 723, 1958. Muller W, Schubothe H: Symptomatische hamolytische Anamie bei Dermoidzysten. Folia Haemat (Frankfurt) 2: 321, 1958. von Miescher P, von Rechenberg HK, Berger J, Hollander L: Hamolytische Ansmie bei Ovarialtumor. Schwejz Med Wschr 88: 498, 1958. Heeres PA, Les Anemies hemolytiques et les kystes de I’ovaire. Sem Hop Paris 36: 1411, 1960. Szirmai E: Symptomatische autoantikorperbedingte hamolytische Anamie bei Erkrankungen der weibli-
17.
18. 19. 20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
then Genitalien. Wein 2 Inn Med 42: 320, 1961. Lorrain C, Del Solar A, Vargas Molinare R: Anemia hemolitica asocida a quiste dermoide del ovario. Sangre 8: 31, 1963. Norcross JW: Hematological manifestations of maligna’nt disease. Med Clin N Amer 47: 345, 1963. McAndrew GM: Haemolytic anemia associated with ovarian teratoma. Brit Med J 2: 1307, 1964. Yam LT, Rudzki C, Busch S, Leithold SL: Ovarian neoplasm associated with autoimmune hemolytic anemia. Amer J Obstet Gynec 95: 207, 1966. Baker LRI, Brain MC, Azzopardi JG, Worlledge SM: Autoimmune haemolytic anaemia associated with ovarian dermoid cyst. J Clin Path 21: 626, 1968. Burkert L, Becker G, Pisciotta AV: Ovarian malignancy and hemolytic anemia. Demonstration of a hemolytic serum factor. Clin Res 17: 531, 1969. Hyman GA, Harvey JE: The pathogenesis of anemia in patients with carcinoma. Amer J Med 19: 350, 1955. Stefanini M, Megalini SI, Patten JH: The relation of neoplastic tissue antigens to autoimmune hematological syndromes. Clin Res Proc 4: 82, 1956. Landaw SA: Hemolytic anemia as a complication of carcinoma. Case report and review of the literature. J Mt Sinai Hosp 31: 167, 1964. Dacie JV: The Haemolytic Anaemies, Congenital and Acquired. Part III, 2nd ed, New York, Grune and Stratton, Inc, 1967, p 785. Suarez CV, Etcheverry MA: A ciste dermoidea del hillo esplenico, esplenomegalial, icteria hemolitica y anemia grava. Arch Argent. de Enferm. d ap. Digest y de la Nutrition 12: 168, 1937. Sande AE: lmmunohaemolytiskanaemi, overvejelser angaende det irregulaere antisotofs oprindehe foranlediget as et tilfaelde af immunhaemolytisk anaemi med santidig forekomst as en mesenterialcyste met et start indhold of antistof. Nord Med 50: 1565, 1953. Sherman JD: The relationship of tumor necrosis to red blood cell changes in the hamster. Blood 14: 1223, 1959. Sherman JD: Further studies on the anemia of the tumor-bearing hamster. J Lab Clin Med 60: 598. 1962.
The American
Journal
of Medlclne
M. ALLEN DAWSON, M.D. WILIMER TALBERT, M.D. JOHN W. YARBRO, M.D.* Lexington, Kentucky
A case of hemolytic anemia secondary to an ovarian tumor is reported. Recognition of this rare cause of hemolytic anemia is important because treatment with corticosteroids and splenectomy has been ineffectual, whereas tumor excision is almost always curative. Our case is unusual in that it is the first thecagranulosa cell tumor .of the ovary found in association with hemolytic anemia; almost all the previous cases were teratomas or adenocarcinomas. Possible mechanisms of the hemolytic anemia are discussed. Hemolytic anemia caused by ovarian tumors has been recognized since the report of West-Watson and Young in 1938 [l]. Although rare, diagnosis is important because excision of the ovarian tumor is almost invariably followed by complete remission of the hemolytic process. Our case represents the twenty-fourth reported case of hemolytic anemia associated with an ovarian tumor -and the fivrst case associated with a probable theta-granulosa type of tumor. CASE REPORT
From the Departments of Medicine and Pathology, University of Kentucky Medical Center, Lexington, Kentucky 40506. Requests for reprints should be addressed to Dr. John W. Yarbro. Manuscript received March 6, 1970. * Present address: American Oncologic Hospital, Philadelphia, Pennsylvania 19111.
552
A forty-one year old white woman (A. O., UKMC No. 10-69-186) was admitted to the University of Kentucky Hospital on September 9, 1968, with complaints of weakness, exertional dyspnea and easy fatigue. She had had no menses for four months except for spotting on one occasion. She had not had abdominal or pelvic pain, fever or jaundice. On physical examination, the oral temperature was 98.6’F, pulse rate 80/minute, respirations 18/minute and blood pressure 144/68 mm Hg. The patient was pale but not acutely ill. There was no icterus or lymphadenopathy. The lungs were clear. The heart was normal except for a vibratory systolic murmur audible over the entire precordium. The liver edge wa’s felt 8 cm below the right costal margin and the spleen 20 cm below the left costal margin. Pelvic examination was normal. The hematocrit was 13 per cent, the hemoglobin 3.8 gm per cent, the white blood count 1,5OO/cu mm, and the platelet count 162,000/ cu mm. The white blood cell differential count showed 56 per cent segmented neutrophils, 32 per cent band forms, 2 per cent metamyelocytes, 6 per cent lymphocytes and 4 per cent monocytes. The peripheral smear showed marked poikilocytosls and 2 nucleated red blood cells were seen/ 100 white blood cells counted. The reticulocyte count was 4,2 per cent. The serum total bllirubin was 0.9 mg per cent. The Coombs test vias negative. The Cr51 red cell survival determlna-
The Amorlc~n
Journal
of Mdlclne
H~OLYTI~
ANEMIA AND OVARIAN TUMOR -
DAWSON ET AL.
tion
showed a half-life of thirteen days, Bone marrow could not be obtained by aspiration from the sternum. A bone marrow biopsy specimen was then obtained from the iliac crest, using a Vim-Silverman needle. This revealed a slight increase in the marrow fibrous tissue and wa’s compatible with myelofibrosis. The patient was given a transfusion of 6 units of packed red blood cells and her condition improved. Corticosteroids were not administered. On discharge from the hospital the hematocrit was 32 per cent. Two months later the hematocrit was 15 per cent and the hemoglobin 6.0 gm per cent; the patient was readmitted to the hospital for splenectomy. A bone marrow biopsy specimen taken from the’ iliac crest revealed hyperplasia of all cell lines with a slight in-. crease in the marrow fibrous tissue. It was thought at this time that she had a myeloproliferative disorder which was not myelofibrosis. At Iaparotomy, the spleen was massively enlarged and was removed. At this point a mass in the right ovary was discovered and excised. The left adrenal gland was abnormal and was removed. Pathologic examination revealed an ovarian tumor that measured 5.5 by 7.5 by 9.5 cm and weighed, 269 gm. The surface of the mass was quite vascular (Figure 1) and the cut surface was soft and yellow-orange. Despite multiple attemps to demonstrate viable tumor tissue, none could be found: the tumor was completely necrotic. However, reticulum stains of the tumor revealed a definite pattern (Figure 2) similar to that found in theta-granulosa cell tumors. The spleen weighed 1600 gm. Innumerable angiomas measuring 3 to 30 mm were present throughout the spleen. (Figures 3, 4, and 5.) On microscopic examination both the liver and spleen contained numerous megakaryocytes in the sinusoidal spaces. The left adrenal gland weighed 22 gm and contained a single nonencapsulated but well circumscribed cortical adenoma. At the time of operation the patient received 8 units of whole blood, after which the hematocrit was 32 per cent and the hemoglobin 9.6 gm per cent. Subsequently, she did not require any further transfusions. The platelet count was elevated, and on several occasions the white blood cell count was moderately elevated. A third bone marrow specimen, obtained from the sternum three months postoperatively, was entirely normal. On July 11, 1969, the patient returned to the hospital because of persistent menorrhagia; she underwent a total hysterectomy. This revealed a uterus weighing 160 gm with extensive adenomyosis. There was a corpus luteum cyst in remaining ovary.
Figure 1. Ovarian tumor with attached and prominent surface vasculature.
Figure
2.
Reticulum
stain
of ovarian
fallopian
tumor
tube
specimen
showing islands of necrotic epithelial cells separated by reticulum-rich fibrous septums. Original magnification x65.
COMMENTS West-Watson
and
ciation
of
Their
patient
whom
Young
hemolytic
,was a forty-four
hemolytic
Volume 50, April
[l]
anemia
1971
anemia
first and year
persisted
noted
the
ovarian old after
assotumor.
woman
in
splenec-
Horizontal section Figure 3. with transmitted light, showing stained. Natural size.
of spleen photographed numerous angiomas. Un-
553
HEMOLYTIC
ANEMIA
AND OVARIAN
TUMOR -
DAWSON
ET AL.
Figure 4. Sinusoidal character of the larger splenic angiomas. Fibrous thickening of the vascular septoms can be seen also. Original magnification x65.
tomy. During a repeat laparotomy in search of an accessory spleen an ovarian teratoma was found and removed after which an immediate and complete remission of the hemolytic anemia occurred. Subsequently, similar cases have been described [2-221 which, including our case, now total twentyfour in the world literature (Table I). Sixteen of the twenty-four ovarian tumors (67 per cent) were teratomas, and of these thirteen were dermoid cysts. Of the remaining eight patients, three had “ovarian cysts,” not further described; four had carcinomas: adenocarcinoma, pseudomucinous cystadenocarcinoma, papillary adenocarcinoma and anaplastic carcinoma; and our patient had a completely necrotic tumor which probably was a theta-granulosa cell tumor. In eleven cases [8-10,12,14,16-211 treatment
Figure 5. Compression of splenic substance by a small angioma. Follicular hyperplasia is not present. Original magnification x65.
554
of the hemolytic anemia was initiated with cot-ticosteroids, which resulted tin transient and slight improvement in the anemia in only four cases [10,17,18,20]. Six patients [1,3,5,10,12,16] underwent splenectomy prior to excision of the ovarian tumor. In two patients [3,10], a temporary remission followed, In all but two of the twenty-four cases the ovarian tumors were removed, which was followed by a complete and usually prompt remission of the hemolytic process except for one patient [5],who died at laparotomy and two patients [18,22] who had widespread metastatic disease from papillary adenocarcinoma. Thus, it is clear that appropriate treatment_ of the hemolytic anemia associated with an ovarian tumor is tumor removal; there seems to be no place for the use of corticosteroids or splenectomy, except in the presence of metastatic disease. Many features ‘in our patient were suggestive of a myeloproliferative disorder. Bone marrow biopsy was interpreted initially as showing an early increase in fibrous tissue, although in retrospect it is probable that it represented a poor biopsy specimen. A subsequent bone marrow biopsy specimen and aspirate showed hyperplasia or normal cellularity. The findings of small foci of megakaryocytes in the splenic sinusoids and liver also are consistent with a myeloproliferative disorder anbd remain unexplained. Finally, postoperative mild leukocytosis and thrombocytosis are in keeping with a myeloproliferative syndrome, although both could be secondary to splenectomy alone. The cause of hemolytic anemia associated with ovarian tumors remains unknown. It has been speculated [23-251 that tumor cells and erythrocytes may share antigens, with development of an autoimmune process. Thmis is indirectly supported by the finding of positive Coombs’ tests in fifteen of the twenty-three cases, although Dacie [26] has emphasized that there is no absolute evidence for an autoimmune process. Landaw [25] has called attention to the fact that in patients with hemolytic anemia secondary to carcinoma, the tumor usually has been an adenocarcinoma, which is a mucinproducing tumor. Possibly the mucin material is antigenic and leads to the development of antibodies which cross react with erythrocytes. In the cases of hemolytic anemia with ovarian tumors th’is speculation is probably more applicable [26] since, in addition to teratomata, adenocarcinomas and other cystic tumors have been found, all of which produce mucin. Hemolytic anemia has also been found in association with a dermoid tumor attached to the hilum of the spleen [26], and in
The American
Journal
of Medicine
z :!
1
2
s
61 23 39
131 I141 1151 I161
3mo
1 yr
9mo
?
1 yr
48
36
52
54
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22
1221 23 Present case
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1
2
Source
Duration of Illness
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+ +
0 ?
+ ?
0 0 0
16 39 20 78 58 74 26 50
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? 4.2
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... ... ...
response response
?
No response
No response ...
Partial Partial
...
No response
... ...
No response
No response
No response No response Short remission ...
... ... ...
... ...
... ... ... ...
Corticosteroids
Cr61 Half-life
Tumors
+
+
0
+ + ?
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+ + + + +
0 ?
+
... +
+ +
test
locytes Coombs
(pm %)
Reticu-
with Ovarian
globin
Associated
Hemo-
Anemia
+ 0 ?
+ + +
+ +
+ ?
+ ?
+ +
Tumor
pable
+ +
megaly
Spleno-
Reported Cases of Hemolytic
Age (yr)
I
Case No.
TABLE
(At time of tumor excision)
(At time of tumor excision) ?
...
...
No effect
...
Short remission ... No effect
... ... ..I ...
No effect
(At time of tumor excision) Short remission ...
No effect
Splenectomy
response Remission
Partial
Remission
Remission
Remission Remission Remission Partial response
Remission Remission Remission
Died at operation Remission Died of transfusion Remission Remission Remission Remission Remission
Remission Slow response
Remission Remission
Tumor Excision
Theta-granulosa
Adenocarcinoma
Teratoma “Cysts” “Cystic degeneration” Dermoid Dermoid Dermoid Papillary adenocarcinoma Dermoid Anaplastic carcinoma Dermoid
Dermoid Pseudomucinous cystadenocarcinema Dermoid Dermoid Dermoid Dermoid Dermoid Dermoid Tetaroma Dermoid
Teratoma “Cyst”
Histologic Diagnosis
HEMOLYTIC
ANEMIA
AND OVARIAN TUMOR -
DAWSON
ET AL.
another case was found to be secondary to a mesenteric cyst which did not originate in the ovary [28]. The patient described by Burkert et al. [22] was shown to have a hemolytic serum factor; when normal red cells were incubated with this patient’s serum for one hour, the autohemolysis test showed 14.5 per cent hemolysis (control 3.0 per cent). There is evidence from animal experiments [29,30] that the injection of necrotic material from tumor extracts into normal animals produces both a shortening of the erythrocyte half-life and hyperactivity of the reticuloendothelial system.
One final point raised by our case concerns the relationship of the splenic angiomas to the hemolytic anemia and their relationship to the ovarian tumor. Data on the spleen in the recorded cases of hemolytic anemia and ovarian tumor are usually limited to the weight of the organ. Splenic angiomas were not described in the reports reviewed. Angiomas could easily have gone undetected if few in number and small. Their relationship to the syndrcme is not clear. Whether they represent a response to products of the tumor or are involved in the mechanism of the hemolysis remains to be elucidated.
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