Endometrial cancer metastasis to brain: Report of two cases and a review of the literature

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Endometrial Cancer Metastasis to Brain : Report of Two Cases and a Review of the Literature Marek Wronski, M .D., Ph.D., Maureen Zakowski, M .D., Ehud Arbit, M .D., William J . Hoskins, M .D., and Joseph H . Galicich, M .D. Memorial Sloan-Kettering Cancer Center, New York, New York

Wronski M, Zakowski M, Arbit E, Hoskins WJ, Galicich JH . Endomerriai cancer metastasis to brain : report of two cases and a review of the literature . Surg Ncurol 1993 ;39 :355-59 . Two cases of brain metastases from endometrial adenocarcinoma are reported . A 70-year-old female presented with lung metastases 14 months after hysterectomy and adjuvant treatment . At 6 months later, a cerebellar metastasis was resected and followed by radiation therapy . The patient died 5 .5 months later . In the second case, a 60-yearold patient developed a lung endometrial metastasis 6 years after initial treatment . At 1 year later she was diagnosed with bilateral hydrocephalus caused by a left temporal and posterior fossa tumor. A ventriculoperitoneal shunt was inserted and she received brain radiation . Two weeks later she gradually became comatose, with right hemiparesis . A metastatic, hemorrhagic temporal tumor was resected but the patient never regained consciousness and died after 7 weeks . The existing literature on brain metastases from endometrial adenocarcinoma is reviewed . KEY WORDS :

Endometrial carcinoma, Brain neoplasm, Brain

metastases

Introduction Although adenocarcinoma of the endometrium is one of the most common gynecological cancers, [5] brain metastases from this tumor are extremely rare . KottkeMarchant et al [18] reported in detail three new cases and compiled 21 other cases, previously reported in autopsies or mentioned in surgical reviews of metastatic brain tumors . We recently treated a patient with adenocarcinoma of the endometrium, metastatic to the cerebellum, where the lesion was neurosurgically extirpated . After a review of the medical records of 640 patients who

Address reprint requests to : Marek Wronski, M .D ., Ph .D ., Research Fellow, Anesthesia and Neurosurgery Service, Room 772A, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY

10021 .

Received August

14, 1992 ;

accepted November

© 1993 by Elsevier Science Publishing Co ., Inc .

10, 1992 .

underwent brain metastasis resection between January 1, 1972 and June 30, 1992 at this institution, we found another patient with metastatic endometrial carcinoma to the brain .

Case 1 A 70-year-old white woman presented in December 1988 with a hemorrhagic vaginal discharge . She underwent a total abdominal hysterectomy with bilateral salpingoopharectomy 2 weeks later . Histology revealed endometrial adenocarcinoma. After surgery she was treated with intravenous combination chemotherapy and whole pelvic irradiation . She did well until February 1990, when she was found to have bilateral lung metastases . Combination chemotherapy did not control the disease, but in May 1990 the patient was treated with tamoxifen and the pulmonary disease stabilized . In September 1990 she presented with a 1-week history of nausea, vomiting, confusion, and lethargy . A computedtomographic (CT) scan of the head revealed a large right and a small left cerebellar lesion with resulting hydrocephalus (Figure 1) . The patient's neurological condition improved on steroids and in September 1990 the large right-sided tumor was resected . Histology revealed metastatic adenocarcinoma similar to the primary uterine tumor resected 22 months earlier . (Figure 2 A, B) . Her postoperative course was uneventful and she was discharged in good neurological condition with clear memory status . From September 20 to October 4 she received whole-brain radiation therapy (WBRT) with a dose of 3000 cGy in 10 fractions . The radiation treatment was well tolerated with no acute side effects except for scalp alopecia. At 2 weeks later the patient developed marked memory loss and disorientation and in midOctober 1990 was again hospitalized . CT and magnetic resonance imaging (MRI) of the head revealed no recurrence of tumor but postradiation changes in the periventricular and subcortical white matter were identified . Another MRI of the head done in January 1991 showed a large right occipital deficit from surgery as well as 0090-3019/9346.00



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I Figure

1 . CT scan of the head with contrast reveals large, enhancing necrotic lesion in the right cerebellar hemisphere. !arrows

encephalomalacia in the right cerebellum . Clinically, she was complaining of problems with balance and continued to have a memory deficit . Her condition seemed to be deteriorating and she was referred to a local hospice . She died at home on February 21, 1991, nearly 5.5 months after brain surgery . An autopsy was not performed.

Case 2 A 60-year-old housewife was in apparent good health until the beginning of 1967 when she had menorrhagia and was found to have an endometrial tumor . In July 1967 she had a total abdominal hysterectomy with bilateral salpingoopharectomy and pathological analysis revealed endometrial adenocarcinoma . After surgery she was given an intravaginal radium implant . She was symptom free until August 1973, when she experienced bilateral chest pain . In November 1973 diagnostic investigations revealed bilateral pleural effusions and the presence of one right, lower-lobe nodule with positive sputum cytology . Thoracocentesis was positive for ade-

nocarcinoma, thought most likely endometrial carcinoma . At that time the patient was placed on combined chemotherapy . In November 1974 she received radiation therapy to the multiple right pleural lesions, consisting of 2800 cGy on the Cobalt 60 parallel-opposed fields . In January 1975 she was admitted with a 1-week history of confusion, headaches, dysmnesia, incoherent speech, and left hemiparesis . The patient's level of consciousness deteriorated ; she was unable to follow commands and became progressively more lethargic . The patient was uncooperative during brain CT scan ; cerebral angiography and pneumoencephalogram were done . These showed symmetrically enlarged lateral and third ventricles, with a large spherical mass in the posterior third ventricle, and tumor stain on the left frontal convexity . An abnormality seen on the posterior fossa suggested metastatic tumor in the left foramen of Monro . A right ventriculoperitoneal shunt was inserted on January 27, 1975 and the patient received 2000 cGy during a rapid (3 days) course of brain radiation . She was discharged on February 15, 1975, and at that time she was oriented to time and place . Motor strength on left side appeared good (4/5), but her gait was slow and widebased. She continued to improve until she fell . This was coincidental with a decrease in her steroid dosage . During the next few days she developed mental deterioration and a right hemiparesis . In March she was readmitted to the hospital lethargic, comatose, incontinent, and extremely dehydrated . A ventriculogram performed through the shunt revealed a marked left-to-right shift and elevation of left temporal lobe. Angiography likewise demonstrated a left temporal mass effect . The preoperative diagnosis was a possible hematoma versus tumor with surrounding edema, Surgery was performed on March 6 and a 3-cm firm, hemorrhagic mass was totally removed, with partial temporal lobectomy . All the brain tissue removed was abnormally soft and may have been necrotic . Pathology revealed metastatic adenocarcinoma, most likely of endometrial lesion . Postoperatively, the patient responded only to painful stimuli and died 7 weeks later . Autopsy was denied by the family . Discussion Uterine endometrial adenocarcinoma is one of the most common gynecological malignancies, and it is estimated that it will be diagnosed in 32,000 American women during 1992 [5] . The incidence of brain metastases, however, is extremely low presumably because endometrial carcinoma belongs to the neurophobic group of cancers, which also includes primary cancer of the prostate, genitourinary carcinoma, various sarcomas, cancer from digestive mucosa, and from endocrine glands [231 . It has



Surg Neurol 1993 ;39 : 3 5 5-59

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A

B

Figure 2 . (A) Metastatic adenocarcinoma to cerebellum . Note rytologic similarities between this and primary endometrial carcinoma (Figure 2 B) (H&E x 400) . (B) Primary adenocarcinoma of endometrium with focal papillary features (H&E x 400) .

system [15] or less frequently through the bloodstream to distant organs . One autopsy study (151 noted that distant metastases were present in 62% of the cases . The lungs represent the most common site (29%) followed by liver, adrenals, kidneys, and spleen [2,15] . In most reported cases of brain metastases from endometrial carcinoma, the metastatic lesion was found located in the supratentorial compartment . This is contrary to the observation made by Delatre et al [11] who has found that the malignancies from the pelvic region usually metastasize to the infratentorial fossa . The high prediliction of the pelvic neoplasm for the posterior fossa was attributed to the direct access to this area by the Batson's plexus, but the authors, however, prefer the "seed and soil" explanation for this phenomena [11] . In both of our cases the metastatic tumor cells most likely reached the cerebellar parenchyma hematogenously through the pulmonary circulation . It is important to note that in our cases as well as in some of the published cases (12,14,18,31] the brain metastasis developed in the late stage of endometrial cancer . Aalder et al [11 reported that in 83 patients with stage-IV endometrial cancer they found only one case of brain metastasis . The same authors, in another paper [2] found 11 patients with metastases to the brain among 379 women with recurrent adenocarcinoma of the endometrium . In our first case, we attribute the failure of long-term survival to treatment with postneurosurgical radiation therapy . There is mounting evidence [10] that wholebrain radiation therapy is not beneficial in patients with gross total resection of brain metastasis . In a group of 185 patients who underwent total removal of a brain metastasis from non-small-cell lung cancer, no difference in median survival was found between the postcraniotomy patients with or without brain radiation [7,36] . The

been suggested that the main reason for the rarity of such metastases is the lack of specific tumor-cell receptors in the central nervous system [24] . We were able to find only 12 other cases of endometrial carcinoma metastatic to the brain reported in detail in the literature . Only one similar case of cerebellar metastasis has been published to date [18], and the patient died 21 days after brain surgery . The results of neurosurgical treatment in all cases are described in Table 1 . According to Willis [34], it was Lorenz [19] who in 1914 first described a patient who had apoplectic symptoms from unsuspected carcinoma of the corpus uteri . The first case of a large, solitary intracerebellar metastasis from endometrial carcinoma was reported by Minkowski in 1941 [201 . In a large neurosurgical series of brain metastases, carcinoma of the uterus was implicated as the primary site in only 0 .5%-4.2% of the cases 1181 . Metastases to the brain from choriocarcinoma [16,32] are found much more frequently than metastases from cervical carcinoma [2 1 or carcinoma of the corpus uteri [9) . Unfortunately, in papers reviewing the autopsy results [4,29] or outcome of treatment of patients with brain metastases, most authors have listed female genital cancer as "genitourinary" [21], "female genital" [4,29), "uterus and adnexa" [13], "other" [7,25], or "rare primary tumors" [381 . Some authors do not distinguish between cervical carcinoma and corpus uterine tumors [30,35,37] making it difficult to analyze data regarding the origin of metastases . Endometrial cancer may spread by local extension to pelvic organs and may spread by the way of the lymphatic



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Table 1 . Results of Surgical Resection of Brain Metastasis from Endometrial Carcinoma Authors (r ef. n o .)

Tumor location

Year

Age

Salibi and Belatos [26]

1972

67

R Fr Pariet

Nakano and Schoene [22]

1975

77

L Occip

Hacker and Fox [14]

1980

80

White et a] [33]

1982

Kishi et al [17}

Interval primary-CNS mess.

Pathology

Follow-up

7 mo

ACA mutinous

NED, 13 mo

26 mo

ACA-clear Ca

DOD, 2 mo

Brain stem

16 yrs

ACA

DOD, 21 days (septicemia)

NA

Supratentorial

NA

NA

DOD, 6-12 mo

1982

NA

Supratentorial

NA

NA

NED, 8 years

Turner and Graff [31}

1982

83

Fr skull + dura

NA

Poorly differ, Ca

DOD, 2 days

Sawada et al [281

1990

43

L Occip

7 weeks

ACA

NED, 7 yrs

Brezinka et at [6]

1990

59

Fr Pariet

7 weeks

ACA

DOD, 23 days (pulm. embol)

Kottke-Marchanr et al [18] Case 1 Case 2 Case 3

1990 1990 1990

59 43 46

R Fr Pariet UP + Post Fossa L Fr Pariet

-3 mo before 1 days -2 .5 mo before

Clear cell Ca. ACA poorly differ. ACA poorly differ.

DOD, 38 mo DOD, 21 days NED, 9 mo

De Porre et a] [12]

1992

67

L Pariet Occip

19 mo

ACA squamous

DOD, 19 days

Wronski et al Case 1 Case 2

1993 1993

70 60

R Cerebellar L Temp + Post Fossa

22 mo 84 mo

ACA ACA

DOD, 5 .5 mo DOD, 7 weeks

R,

Abbreviations : ACA, adenocarcinoma; NA, not available ; DOD, died of disease ; NED, no evidence of disease ; Fr, frontal; differ., differentiated ; Ca, carcinoma, right; L, left, Pariet, parietal ; Occip, occipital, Temp, temporal .

number of recurrences in both groups was similar, but the percentage of patients alive to last follow-up was 15% in the group not receiving WBRT compared with 5% in the radiated group [36] . A new treatment modality of brain metastases with radiosurgery is currently under investigation. Preliminary, favorable results are reported [3,9] but long-term data on follow-up and complications (e .g ., dementia and radiation necrosis) are not yet available . The role of adjuvant radiotherapy after gross total resection of a cerebral metastasis is yet to be determined . Our perception, not based on a randomized study, is that after complete resection of a known radioresistant tumor, brain irradiation should be withheld . In conclusion, in women with previously diagnosed endometrial adenocarcinoma, a solitary brain metastasis, albeit exceptionally rare, should be considered in the differential diagnosis of any neurological symptoms suggesting the possibility of an intracerebral tumor .

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