Choroid plexus carcinoma Case report
GEORGE J. DOHRMANN, M.D., PH.D., AND JAMES C. COLLIAS, M.D.
Sections of Neurosurgery and Neuropathology, Yale University School of Medicine, New Haven, and Department of Neurosurgery, Hartford Hospital, Hartford, Connecticut The authors report a case of carcinoma of the choroid plexus and review the 22 cases reported since 1844 that adhere to the criteria for primary choroid plexus carcinoma. Two-thirds of the tumors are found in children and all of these are located in the lateral ventricles. In adults most of the tumors are present in the fourth ventricle. Differentiation of this neoplasm from papillary ependymomas, choroid plexus papillomas, secondary carcinomas, and "collision tumors" is discussed. KEY WORDS choroid plexus 9 carcinoma fourth ventricle 9 posterior fossa neoplasm ~
p
RIMARY carcinoma of the choroid plexus is rare. In 1844, Rokitansky a~ described a medullary tumor arising from the choroid plexus. Approximately 60 cases have been reported as choroid plexus carcinoma since then, but the validity of some of these diagnoses remained in doubt. Many of these cases did not fulfill the histological criteria of primary carcinoma of the choroid plexus. The remainder were papillomas, other malignant neoplasms, or secondary carcinomas. The purpose of this paper is twofold: l) to review and analyze previously published cases of choroid plexus carcinoma with regard to sex, age, location, histological presentation and duration from onset of symptoms to death; and 2) to report a new case of primary carcinoma of the choroid plexus.
J. Neurosurg. / Volume 43 / August, 1975
9
Case Report This 55-year-old woman was in relatively good health until 3 months prior to admission when she noted increasing difficulty in keeping her balance. One month prior to admission she described "blurring" of her vision, intermittent diplopia, and occasional nausea and vomiting. One week prior to admission a moderate right frontal headache was noted. Examination. A general physical examination was within normal limits. She had a blood pressure of 130/80, no cranial or neck bruits, no neck stiffness, and unremarkable carotid pulses. On neurological examination she was alert and exhibited normal mentation. Examination of the cranial nerves revealed no abnormalities other than a longstanding minimal nerve deafness on the left. No papilledema or hemorrhages were noted 225
G. J. Dohrmann and J. C. Collias
FIG. 1. Skull film showing midline calcification in the posterior fossa.
Fl~. 2. Left vertebral angiotomogram demonstrating central tumor stain in the posterior fossa.
on funduscopic examination. The patient had normal reflexes, with good motor function in all extremities. The plantar responses were flexor, and no sensory abnormalities were present. Nystagmus was seen in all directions of gaze, and dysmetria was noted on the left, but no dysdiadochokinesia was present. The gait was broad-based and the patient had a tendency to fall to the left. Laboratory tests included a complete blood count, serology, serum electrolyte determination, and urinalysis. These were all within the normal range. A lumbar puncture was performed and an opening pressure of 150 mm of water noted. The cerebrospinal fluid (CSF) was clear and colorless and had 130 mg% protein, 64 mg% sugar, 23 erythrocytes, 3 leukocytes, and normal cell block cytology. 226
Cultures of CSF were negative for bacteria and fungi. High-amplitude intermittent slow activity was seen bitemporally on the electroencephalogram. The brain scan was normal. A chest x-ray film was unremarkable, while some midline calcification in the posterior fossa region was noted on skull xray films (Fig. 1). Polytomography of the posterior fossa and temporal bones revealed a well-defined, homogeneous, calcified 1 • 2 cm density in the midline of the posterior fossa. The temporal bones were normal in appearance. Cerebral angiography and angiotomography of the posterior fossa were performed. The choroidal point of the left posterior inferior cerebellar artery was displaced inferoanteriorly. A well-marginated tumor stain was noted centrally and slightly to the left of the midline in the posterior fossa (Fig. 2). Operation. A suboccipital craniectomy was performed and the cerebellar vermis was split; this revealed a brownish-gray moderately soft tumor. The neoplasm was approximately 6 • 4 cm and appeared to fill the entire fourth ventricle. It was calcified and adherent in the region of the facial colliculi but was otherwise readily separable from the floor of the fourth ventricle. Except for the left superior region of the cerebellum, where the tumor appeared to merge with the cerebellum, the tumor was separated easily from the surrounding cerebellar tissue. One small area of apparent necrosis was present. Histopathology. Much of the neoplasm was composed of numerous villi, low columnar cells arranged in a single layer enveloping a small fibrovascular center (Fig. 3 upper left). In one portion of the neoplasm, a transition from regularly arranged epithelial cells to irregularly arranged pleomorphic cells was noted (Fig. 3 upper right). A breakdown of the epithelial-villus architecture was present with invasion of portions of adjacent neural tissue. In one area, cells in a villus-like configuration as well as malignant-appearing cells with no apparent organization were noted within neural tissue (Fig. 3 lower left and right). The choroidal cells did not react to periodic acid-Schiff or mucin staining. Although small areas of calcification were present throughout the tumor, a larger area of calcification and some metaplastic bone was noted within an enlarged fibrovascular stroma.
J. Neurosurg. / Volume 43 / August, 1975
Choroid plexus carcinoma
FIG. 3. Upper Left: Photomicrograph of a benign-appearing portion of the tumor. A single layer of low columnar cells is regularly arranged over a thin central fibrovascular stroma. PAS and hematoxylin, x 350. Upper Right." Photomicrograph demonstrating the transition from more normal-appearing choroidal epithelial cells (arrow) to pleomorphic cells just below. Area of invasion by pleomorphic cells lies to the left of the arrow. PAS and hematoxylin, X 875. Lower Left." Photomicrograph showing invasion of surrounding neural tissue by cells in a villus-like arrangement (arrows). PAS and hematoxylin, x 350. Lower Right: Photomicrograph showing invasion by pleomorphic cells in a random arrangement adjacent to a thin-walled blood vessel. PAS and hematoxylin, • 1400.
J. Neurosurg. / Volume 43 / August, 1975
227
G. J. Dohrmann and J. C. Collias TABLE 1
Summary of cases reported as choroid plexus carcinoma* Author, Year
Onset of Symptoms to Death
Age (yrs)
Sex
Rokitansky, 1844 Spaet, 1883 Saxer, 1902
-38 51
-M M
-8 --
4th multiple 4th
Bielschowsky & Unger, 1906 Kolpin, 1909 Boudet & Clunet, 1910 Hart, 1910 van Bouwdijk Bastiaanse, 1914 Korner, 1919
43 53 45 50 59 42
F F M F F M
26 16 8 12 11 52
4th multiple rt lateral multiple multiple 4th
9 7
M M
-2
rt lateral 4th
Kono, 1924
31
M
16
It lateral
Davis & Cushing, 1925 Noodt, 1925 Toppich, 1925 Esser, 1926 Lehoczky, 1928 Zand & Mackiewitz, 1929 Hall & Fentress, 1933 Dandy, 1934
30 33 2 22 27 14 61 20(mos)
F F M M F M M M
72 8 12 6 6 2 52 6
4th 3rd 4th 4th 4th 3rd multiple It lateral
Faber, 1934 Graves & Fliess, 1934
29 M 9(raps) M
2 4
rt lateral It lateral
possibly secondary carcinoma primary malignant choroid
3rd 3rd 3rd -4th 4th It lateral 3rd rt lateral rt lateral
neoplasm ? probably glioma possibly secondary carcinoma probably secondary carcinoma carcinomatous meningitis secondary carcinoma choroid plexus papilloma ? choroid plexus papilloma ? unable to assess choroid plexus papilloma primary malignant choroid neoplasm
Zdrahal, 1936 Turner & Simon, 1937 Mussaelian, 1940 Berger, 1942 Walker & Horrax, 1947 Wilkins, et aL, 1948 Ringertz & Reymond, 1949 Zander, 1949 Vraa-Jensen, 1950
10 27 57 40 53 44 6 33 26 7
(wks)
F F M M M M M F M F
208 56 48 -20 > 572 > 208 26 > 64 208
Ventricle Site
Histological Review possibly ependymoma probably secondary carcinoma probably choroid plexus papilloma secondary carcinoma secondary carcinoma choroid plexus papilloma secondary carcinoma secondary carcinoma choroid plexus papilloma choroid plexus papilloma probably papillary ependymoma probably choroid plexus papilloma choroid plexus papilloma choroid plexus papilloma possibly ependymoma malignant choroid plexus tumor ? choroid plexus papilloma glial origin? probably secondary carcinoma primary malignant choroid neoplasm ?
* Modified, in part, after Lewis (ref. 23). Histology reported in italics denoted primary carcinoma of the choroid plexus. t Reported six cases of malignant change in choroid plexus ol lateral ventricles but gave no other specific information, including criteria for malignancy and published histology. :~Another case cited by Zulch (ref. 47) has been reported previously by van Hoytema and Winckel (ref. 39). wFour cases of choroid plexus carcinoma are cited in children between the ages of 2 and 4 years, but no other details are given.
228
J. Neurosurg. / Volume 43 / August, 1975
Choroid plexus carcinoma TABLE 1 (Continued)
Author, Year
Age (yrs)
Sex
Onset of Symptoms to Death (wks)
Ventricle Site
Lindenberg, 1951 Cardauns, 1957
41 23
M M
312 182
van Hoytema & Winckel, 1957
10(mos) M
8
It lateral
Dufek, 1959 Loginov, 1960
31 4
F F
20 6
rt lateral rt lateral
2
F
30
rt lateral
4(mos) F
10
It lateral
9(mos) M 20(mos) F
> 156 3
It lateral It lateral
Matson & Crofton, 1960
--
--
17(mos) M
6
3rd 4th
Bohm & Strang, 1961t (6 cases) Vinken & Slooff, 1965
--
Zulch, 1965++
23
Lewis, 1967
20(mos) F
130
It lateral
23(mos) F
20
It lateral rt lateral
M
--
Histological Review benign, ?type
malignant ehoroM plexus neoplasm ? primary malignant ehoroid neoplasm ? choroid plexus papilloma ?
primary malignant ehoroid neoplasm primary malignant ehoroid neoplasm ? prhnary malignant ehoroid neoplasm ? choroid plexus papilloma ?
primary malignant choroid neoplasm ?
lateral
insufficient information
It lateral
primary malignant neoplasm ? primary malignant neoplasm primary malignant neoplasm primary malignant neoplasm primary malignant neoplasm primary malignant neoplasm ?
--
4
M
20
Tham, et al., 1969
66
F
520
Banna, 1971
ll(mos) M
> 130
rt lateral
Brochu & Lefebvre, 1971
53
M
6
rt lateral
Russell & Rubinstein, 1971w
2 to 4
4 cases
--
--
Shuangshoti, et al., 1971
47
M
12
rt lateral
D o h r m a n n & Collias, 1975
55
F
> 52
4th
4th
choroid choroid choroid ehoroid choroid choroid
malignant papillary neoplasm, ? source malignant papillary neoplasm, ? source
primary malignant choroid neoplasms primary malignant choroid neoplasm ? primary malignant choroid neoplasm
* Modified, in part, after Lewis (ref. 23). Histology reported in italics denotes primary carcinoma of the choroid plexus. f Reported six cases of malignant change in choroid plexus ol lateral ventricles but gave no other specific information, including criteria for malignancy and published histology. ~/Another case cited by Zulch (ref" 47) has been reported previously by van Hoytema and Winckel (ref. 39). wFour cases of choroid plexus carcinoma are cited in children between the ages of 2 a n d 4 years, but no other details are given.
J. Neurosurg. / Volume 43 / August, 1975
229
G. J. Dohrmann and J. C. Collias Postoperative Course. The patient had bilateral sixth and seventh nerve palsies postoperatively. The ataxia and dysmetria improved as did the nystagmus. She was seen after the termination of her radiation therapy, 4 months postoperatively, at which time her gait had improved and the right facial palsy had begun to resolve. Presently, she is at h o m e and has resumed activity. Discussion The light and electron microscopy of human choroid plexus has been reported ~,12 and the structure, function, and pathology of the choroid plexus has been reviewed elsewhere.I~ With the present case included, 61 cases have been reported as carcinoma of the choroid plexus since the initial mention of it as a rarity by Rokitansky 3~in 1844 (Table 1). Whether or not the neoplasm is termed a " p r i m a r y choroid plexus carcinoma" depends upon the criteria used. The strictest criteria are those of Russell and Rubinstein 31 and Lewis, 23 and are as follows: 1) invasion of the adjacent neural tissue with infiltrating cells that assume a diffuse growth pattern; 3~ 2) loss of the regular papillary structure of the neoplasm, at least where invasion is occurring, and obvious malignant alterations in the cells; 8~ and 3) transition of normal choroid plexus architecture to an undifferentiated pattern. 23 The neoplasm described in this article was diagnosed as carcinoma of the choroid plexus since it complies with these three criteria. Papillary ependymomas, choroid plexus papillomas, m e t a s t a t i c carcinomas, and "collision tumors" (carcinoma metastatic to a choroid plexus papilloma) should be included in the differential diagnosis of car-
cinoma of the choroid plexus. Papillary ependymomas would have a fibrillary neuroglial stroma and blepharoplasts in the epithelial cells, while choroidal neoplasms would not. sx Papillomas of the choroid plexus would conform to normal choroid plexus architecture and cytology. S u b a r a c h n o i d spread or "seeding" may be noted with either benign or malignant choroidal neoplasms. 28 The most common metastatic carcinoma that might be mistaken for a malignant choroid plexus neoplasm is bronchogenic carcinoma. If there is no reaction on periodic acid-Schiff and mucin staining and a negative chest x-ray film, metastatic bronchogenic carcinoma would tend to be unlikely; however, a very small primary carcinoma in the lung may never be excluded. If massive necrosis is noted, it is usually associated with metastatic papillary adenocarcinoma and is not seen in primary choroidal carcinoma. 47 "Collision tumors" would not have areas of transition from normal choroidal epithelium to an undifferentiated pattern with histological manifestations of malignancy. Twenty-two cases of carcinoma of the choroid plexus, including the present case, have been reported that largely fulfill the previously listed criteria. Sixteen of these occurred in children and six in adults; sex distribution was equal. The mean age of afflicted children was 2.5 years while in adults it was 39 years. Children succumbed from the disease after a shorter course; the time from onset of s y m p t o m s to death was approximately 9 months in children and 3.5 years in adults. All of the choroid plexus carcinomas in children occurred in the lateral ventricles (67% left; 33% right), while most of the tumors in adults were located in the fourth ventricle (Table 2).
TABLE 2
Summary of 22 cases of primary carcinoma of the choroid plexus
Patients
children (16) adults (6) overall (22) 230
Sex (%) M F
Mean Age (yrs)
Time of Onset of Symptoms to Death
42 67 50
2.5 39 12.5
9 mos 3.5 yrs 1.4 yrs
58 33 50
Ventricle Location (%) Rt Lt Lateral Lateral 3rd 4th 33 20 30
67 0 47
0 0 0
0 80 23
J. Neurosurg. / Volume 43 / August, 1975
Choroid plexus carcinoma References 1. Banna M: Angiography of malignant choroid plexus papilloma. Br J Radiol 44:412-415, 1971 2. Berger M: Metastasierendes Papillom des Plexus chorioideus ventriculi IV. Zentralbl AIIg Pathol 80:5-9, 1942 3. Bielsehowsky M, Unger E: Zur Kenntniss der primaren Epithelgeschwiilste der Adergeflechte des Gehirns. Langenbecks Arch Chit 81:61-82, 1906 4. Bohm E, Strung R: Choroid plexus papillomas. J Neurosurg 18:493-500, 1961 5. Boudet G, Clunet J: Contribution h l'6tude des tumeurs 6pith61iales primitives de r6nc6phale. D6velopp6es aux d6pens des formations 6pendymaires et particuli~rement des plexus choroides. Arch M6d Exp 22:379-411, 1910 6. Brochu P, Lefebvre R: Ad6nocarcinome papillaire mucipare multicentrique des plexus choroides. Union M6d Can 100:1787-1789, 1971 7. Cardauns H: Crber ein malignes Plexuspapillom. Zentralbl Neurochir 17:349-353, 1957 8. Dandy WE: Benign, Encapsulated Tumors in the Lateral Ventricles of the Brain. Diagnosis and Treatment. Baltimore, Williams and Wilkins, 1934 9. Davis LE, Cushing H: Papillomas of the choroid plexus. With report of six cases. Arch Neurol Psychiatry 13:681-710, 1925 10. Dohrmann G J: The choroid plexus: a historical review. Brain Res 18:197-218, 1970 11. Dohrmann G J: Dark and light epithelial cells in the choroid plexus of mammals. J Ultrastruct Res 32:268-273, 1970 12. Dohrmann GJ, Bucy PC: Human choroid plexus: a light and electron microscopic study. J Nenrosurg 33:506--516, 1970 13. Dufek H: Zur Frage des prim~iren Carcinoms des Plexus chorioideus. Zentralbi AIIg Pathol 100:136-142, 1959 14. Esser A: Ein Carcinom des Plexus chorioideus des 4 Ventrikels. Z Gesamtel Neurol Psychiatr 106:511-517, 1926 15. Faber V: Fall yon carcinomat5s entartetem Papillom des Seitenventrikels. Frankfurt Z Pathol 47:168-172, 1934 16. Graves GW, Fliess MM: Neoplasm of the choroid plexus. Report of a case with review of the literature. Am J Dis Child 47:97-103, 1934 17. Hall GW, Fentress TL: Papilloma choroideum with diffuse central nervous system metastases. J Neurol Psychopathoi 14:108-115, 1933 18. Hart K: Ueber prim~ire epitheliale Geschw[iiste des Gehirns; zugleich Untersuchungen und Betrachtungen fiber das Ependymepithel. Arch Psyehiatr Nervenkr 47: 739-773, 1910
J. Neurosurg. / Volume 43 / August, 1975
19. K~51pin O: Multiple Papillome (AdenoCarcinome) des Gehirns. Arch Psychiatr Nervenkr 45:595-604, 1909
20. Kono N: Ober Implantatinsmetastasen im Subarachnoidalraum, zugleich ein Beitrag zur Frage der LiquorstriSmung. Frankfurt Z Pathol 30:92-103, 1924 21. KSrner H: Geschw~ilste der Adergeflechte. Zentralbl AIIg Pathol 30:121-135, 1919 22. Lehoczky von T: Zur Frage der prim~iren Gehirncarcinome. Arch Psychiatr Nervenkr 82:527-566, 1928 23. Lewis P: Carcinoma of the choroid plexus. Brain 90:177-186, 1967 24. Lindenberg R: Ober ein Plexusepitheliom des 3 Ventrikels mit geschichtetem Plattenepithel und einer Auskleidung der Ventrikelwand mit dem gleichen Epithel. Zentralbi Alig Pathol 88:47-51, 1951 25. Loginov EN: (Primary cancer of the choroid plexus in a child). Arkh Patol 22:63-65, 1960
(Rus)
26. Matson DD, Crofton FDL: Papilloma of the choroid plexus in childhood. J Neuroserg 17:1002-1027, 1960 27. Mussaelian SK: (On the diffuse malignant epitheliome of the vascular plexus). Neuropatoi Pslkh 9:77-80, 1940 (Rus) 28. Noodt K: Ein Beitrag zur Kenntnis der papill~iren Epitheliome des Plexus chorioideus. Virchows Arch (Pathol Anat) 258:331-336, 1925 29. Ringertz N, Reymond A: Ependymomas and choroid plexus papillomas. J Neuropathol Exp Neurol 8:355-380, 1949 30. Rokitansky C: Handbuch der speciellen pathologischen Anatomic. Vol 1. Vienna, Braumiiller and Seidel, 1844 31. Russell DS, Rubinstein L J: Pathology of Turnouts of the Nervous System. ed 2. London, E Arnold, 1971 32. Saxer F: Ependymepithel, Gliome und epitheliale Geschwiilste des Centralnervensystems. Beitr Pathol 32:276-350, 1902 33. Shuangshoti S, Tangchai P, Netsky MG: Primary adenocarcinoma of the choroid plexus. Arch Pathol 91:101-106, 1971 34. Spaet F: Prim~irer multipler Epithelkrebs des Gehirns. Aertzl Int-BI 30:305-307, 1883 35. Tham KT, Wen HL, Teoh TB: A case of papillary adenocarcinoma of the choroid plexus. J Pathol 99:321-324, 1969 36. TiSppich G: Die Zottenkrebse des Adergeflechtes der Rautengrube. Frankfurt Z Pathol 33:238-247, 1925 37. Turner OA, Simon MA: Malignant papillomas of the choroid plexus. Report of two cases with a review of the literature. Am J Cancer 30:289-297, 1937 38. van Bouwdijk Bastiaanse FS: Prim~ires, 231
G. J. Dohrmann and J. C. Collias
39. 40. 41. 42. 43. 44. 45.
232
metastatasierendes Gehirncarcinom. Z Ges Neurol Psychiatr 27:96-108, 1915 van Hoytema G J, Winckel WEF: Zur Frage des prim~iren Plexuskarzinoms. Zentralbl Neurochir 17:353-363, 1957 Vinken P J, Slooff ACJ: A case of carcinoma of the choroid plexus in a child. Zentralbl Neurochir 26:313-317, 1965 Vraa-Jensen G: Papilloma of the choroid plexus with pulmonary metastases. Acta Psychiatr Neuroi 25:299-306, 1950 Walker JC, Horrax G: Papilloma of the choroid plexus. With report of an unusual case. J Neurosurg 4:387-391, 1947 Wilkins H, Smith R, Halpert B: Neoplasm of the choroid plexus of the left lateral ventricle. J Neurosurg 5:406-410, 1948 Zand N, Mackiewitz J: Papillome malin du plexus choroide. Eneephale 24:841-845, 1929 Zander E: 6 F/ille yon Papillomen des Plexus
chorioideus. Monatschr Psychiatr Neurol 118:321-363, 1949 46. Zdrahal N: Ein Fall yon Karzinom des Plexus chorioideus mit ungewohnlichen klinischen Erscheinungen. Arch Kinderhlkd 109:24-29, 1936 47. Ziilch KJ: Brain Tumors: Their Biology and Pathology, ed 2. New York, Springer-Verlag, 1965
This work was supported in part by Grant NS 10174 from the National Institute of Neurological Diseases and Stroke. Address reprint requests to: George J. Dohrmann, M.D., Ph.D., Sections of Neurosurgery and Neuropathology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510.
J. Neurosurg. / Volume 43 / August, 1975
GEORGE J. DOHRMANN, M.D., PH.D., AND JAMES C. COLLIAS, M.D.
Sections of Neurosurgery and Neuropathology, Yale University School of Medicine, New Haven, and Department of Neurosurgery, Hartford Hospital, Hartford, Connecticut The authors report a case of carcinoma of the choroid plexus and review the 22 cases reported since 1844 that adhere to the criteria for primary choroid plexus carcinoma. Two-thirds of the tumors are found in children and all of these are located in the lateral ventricles. In adults most of the tumors are present in the fourth ventricle. Differentiation of this neoplasm from papillary ependymomas, choroid plexus papillomas, secondary carcinomas, and "collision tumors" is discussed. KEY WORDS choroid plexus 9 carcinoma fourth ventricle 9 posterior fossa neoplasm ~
p
RIMARY carcinoma of the choroid plexus is rare. In 1844, Rokitansky a~ described a medullary tumor arising from the choroid plexus. Approximately 60 cases have been reported as choroid plexus carcinoma since then, but the validity of some of these diagnoses remained in doubt. Many of these cases did not fulfill the histological criteria of primary carcinoma of the choroid plexus. The remainder were papillomas, other malignant neoplasms, or secondary carcinomas. The purpose of this paper is twofold: l) to review and analyze previously published cases of choroid plexus carcinoma with regard to sex, age, location, histological presentation and duration from onset of symptoms to death; and 2) to report a new case of primary carcinoma of the choroid plexus.
J. Neurosurg. / Volume 43 / August, 1975
9
Case Report This 55-year-old woman was in relatively good health until 3 months prior to admission when she noted increasing difficulty in keeping her balance. One month prior to admission she described "blurring" of her vision, intermittent diplopia, and occasional nausea and vomiting. One week prior to admission a moderate right frontal headache was noted. Examination. A general physical examination was within normal limits. She had a blood pressure of 130/80, no cranial or neck bruits, no neck stiffness, and unremarkable carotid pulses. On neurological examination she was alert and exhibited normal mentation. Examination of the cranial nerves revealed no abnormalities other than a longstanding minimal nerve deafness on the left. No papilledema or hemorrhages were noted 225
G. J. Dohrmann and J. C. Collias
FIG. 1. Skull film showing midline calcification in the posterior fossa.
Fl~. 2. Left vertebral angiotomogram demonstrating central tumor stain in the posterior fossa.
on funduscopic examination. The patient had normal reflexes, with good motor function in all extremities. The plantar responses were flexor, and no sensory abnormalities were present. Nystagmus was seen in all directions of gaze, and dysmetria was noted on the left, but no dysdiadochokinesia was present. The gait was broad-based and the patient had a tendency to fall to the left. Laboratory tests included a complete blood count, serology, serum electrolyte determination, and urinalysis. These were all within the normal range. A lumbar puncture was performed and an opening pressure of 150 mm of water noted. The cerebrospinal fluid (CSF) was clear and colorless and had 130 mg% protein, 64 mg% sugar, 23 erythrocytes, 3 leukocytes, and normal cell block cytology. 226
Cultures of CSF were negative for bacteria and fungi. High-amplitude intermittent slow activity was seen bitemporally on the electroencephalogram. The brain scan was normal. A chest x-ray film was unremarkable, while some midline calcification in the posterior fossa region was noted on skull xray films (Fig. 1). Polytomography of the posterior fossa and temporal bones revealed a well-defined, homogeneous, calcified 1 • 2 cm density in the midline of the posterior fossa. The temporal bones were normal in appearance. Cerebral angiography and angiotomography of the posterior fossa were performed. The choroidal point of the left posterior inferior cerebellar artery was displaced inferoanteriorly. A well-marginated tumor stain was noted centrally and slightly to the left of the midline in the posterior fossa (Fig. 2). Operation. A suboccipital craniectomy was performed and the cerebellar vermis was split; this revealed a brownish-gray moderately soft tumor. The neoplasm was approximately 6 • 4 cm and appeared to fill the entire fourth ventricle. It was calcified and adherent in the region of the facial colliculi but was otherwise readily separable from the floor of the fourth ventricle. Except for the left superior region of the cerebellum, where the tumor appeared to merge with the cerebellum, the tumor was separated easily from the surrounding cerebellar tissue. One small area of apparent necrosis was present. Histopathology. Much of the neoplasm was composed of numerous villi, low columnar cells arranged in a single layer enveloping a small fibrovascular center (Fig. 3 upper left). In one portion of the neoplasm, a transition from regularly arranged epithelial cells to irregularly arranged pleomorphic cells was noted (Fig. 3 upper right). A breakdown of the epithelial-villus architecture was present with invasion of portions of adjacent neural tissue. In one area, cells in a villus-like configuration as well as malignant-appearing cells with no apparent organization were noted within neural tissue (Fig. 3 lower left and right). The choroidal cells did not react to periodic acid-Schiff or mucin staining. Although small areas of calcification were present throughout the tumor, a larger area of calcification and some metaplastic bone was noted within an enlarged fibrovascular stroma.
J. Neurosurg. / Volume 43 / August, 1975
Choroid plexus carcinoma
FIG. 3. Upper Left: Photomicrograph of a benign-appearing portion of the tumor. A single layer of low columnar cells is regularly arranged over a thin central fibrovascular stroma. PAS and hematoxylin, x 350. Upper Right." Photomicrograph demonstrating the transition from more normal-appearing choroidal epithelial cells (arrow) to pleomorphic cells just below. Area of invasion by pleomorphic cells lies to the left of the arrow. PAS and hematoxylin, X 875. Lower Left." Photomicrograph showing invasion of surrounding neural tissue by cells in a villus-like arrangement (arrows). PAS and hematoxylin, x 350. Lower Right: Photomicrograph showing invasion by pleomorphic cells in a random arrangement adjacent to a thin-walled blood vessel. PAS and hematoxylin, • 1400.
J. Neurosurg. / Volume 43 / August, 1975
227
G. J. Dohrmann and J. C. Collias TABLE 1
Summary of cases reported as choroid plexus carcinoma* Author, Year
Onset of Symptoms to Death
Age (yrs)
Sex
Rokitansky, 1844 Spaet, 1883 Saxer, 1902
-38 51
-M M
-8 --
4th multiple 4th
Bielschowsky & Unger, 1906 Kolpin, 1909 Boudet & Clunet, 1910 Hart, 1910 van Bouwdijk Bastiaanse, 1914 Korner, 1919
43 53 45 50 59 42
F F M F F M
26 16 8 12 11 52
4th multiple rt lateral multiple multiple 4th
9 7
M M
-2
rt lateral 4th
Kono, 1924
31
M
16
It lateral
Davis & Cushing, 1925 Noodt, 1925 Toppich, 1925 Esser, 1926 Lehoczky, 1928 Zand & Mackiewitz, 1929 Hall & Fentress, 1933 Dandy, 1934
30 33 2 22 27 14 61 20(mos)
F F M M F M M M
72 8 12 6 6 2 52 6
4th 3rd 4th 4th 4th 3rd multiple It lateral
Faber, 1934 Graves & Fliess, 1934
29 M 9(raps) M
2 4
rt lateral It lateral
possibly secondary carcinoma primary malignant choroid
3rd 3rd 3rd -4th 4th It lateral 3rd rt lateral rt lateral
neoplasm ? probably glioma possibly secondary carcinoma probably secondary carcinoma carcinomatous meningitis secondary carcinoma choroid plexus papilloma ? choroid plexus papilloma ? unable to assess choroid plexus papilloma primary malignant choroid neoplasm
Zdrahal, 1936 Turner & Simon, 1937 Mussaelian, 1940 Berger, 1942 Walker & Horrax, 1947 Wilkins, et aL, 1948 Ringertz & Reymond, 1949 Zander, 1949 Vraa-Jensen, 1950
10 27 57 40 53 44 6 33 26 7
(wks)
F F M M M M M F M F
208 56 48 -20 > 572 > 208 26 > 64 208
Ventricle Site
Histological Review possibly ependymoma probably secondary carcinoma probably choroid plexus papilloma secondary carcinoma secondary carcinoma choroid plexus papilloma secondary carcinoma secondary carcinoma choroid plexus papilloma choroid plexus papilloma probably papillary ependymoma probably choroid plexus papilloma choroid plexus papilloma choroid plexus papilloma possibly ependymoma malignant choroid plexus tumor ? choroid plexus papilloma glial origin? probably secondary carcinoma primary malignant choroid neoplasm ?
* Modified, in part, after Lewis (ref. 23). Histology reported in italics denoted primary carcinoma of the choroid plexus. t Reported six cases of malignant change in choroid plexus ol lateral ventricles but gave no other specific information, including criteria for malignancy and published histology. :~Another case cited by Zulch (ref. 47) has been reported previously by van Hoytema and Winckel (ref. 39). wFour cases of choroid plexus carcinoma are cited in children between the ages of 2 and 4 years, but no other details are given.
228
J. Neurosurg. / Volume 43 / August, 1975
Choroid plexus carcinoma TABLE 1 (Continued)
Author, Year
Age (yrs)
Sex
Onset of Symptoms to Death (wks)
Ventricle Site
Lindenberg, 1951 Cardauns, 1957
41 23
M M
312 182
van Hoytema & Winckel, 1957
10(mos) M
8
It lateral
Dufek, 1959 Loginov, 1960
31 4
F F
20 6
rt lateral rt lateral
2
F
30
rt lateral
4(mos) F
10
It lateral
9(mos) M 20(mos) F
> 156 3
It lateral It lateral
Matson & Crofton, 1960
--
--
17(mos) M
6
3rd 4th
Bohm & Strang, 1961t (6 cases) Vinken & Slooff, 1965
--
Zulch, 1965++
23
Lewis, 1967
20(mos) F
130
It lateral
23(mos) F
20
It lateral rt lateral
M
--
Histological Review benign, ?type
malignant ehoroM plexus neoplasm ? primary malignant ehoroid neoplasm ? choroid plexus papilloma ?
primary malignant ehoroid neoplasm primary malignant ehoroid neoplasm ? prhnary malignant ehoroid neoplasm ? choroid plexus papilloma ?
primary malignant choroid neoplasm ?
lateral
insufficient information
It lateral
primary malignant neoplasm ? primary malignant neoplasm primary malignant neoplasm primary malignant neoplasm primary malignant neoplasm primary malignant neoplasm ?
--
4
M
20
Tham, et al., 1969
66
F
520
Banna, 1971
ll(mos) M
> 130
rt lateral
Brochu & Lefebvre, 1971
53
M
6
rt lateral
Russell & Rubinstein, 1971w
2 to 4
4 cases
--
--
Shuangshoti, et al., 1971
47
M
12
rt lateral
D o h r m a n n & Collias, 1975
55
F
> 52
4th
4th
choroid choroid choroid ehoroid choroid choroid
malignant papillary neoplasm, ? source malignant papillary neoplasm, ? source
primary malignant choroid neoplasms primary malignant choroid neoplasm ? primary malignant choroid neoplasm
* Modified, in part, after Lewis (ref. 23). Histology reported in italics denotes primary carcinoma of the choroid plexus. f Reported six cases of malignant change in choroid plexus ol lateral ventricles but gave no other specific information, including criteria for malignancy and published histology. ~/Another case cited by Zulch (ref" 47) has been reported previously by van Hoytema and Winckel (ref. 39). wFour cases of choroid plexus carcinoma are cited in children between the ages of 2 a n d 4 years, but no other details are given.
J. Neurosurg. / Volume 43 / August, 1975
229
G. J. Dohrmann and J. C. Collias Postoperative Course. The patient had bilateral sixth and seventh nerve palsies postoperatively. The ataxia and dysmetria improved as did the nystagmus. She was seen after the termination of her radiation therapy, 4 months postoperatively, at which time her gait had improved and the right facial palsy had begun to resolve. Presently, she is at h o m e and has resumed activity. Discussion The light and electron microscopy of human choroid plexus has been reported ~,12 and the structure, function, and pathology of the choroid plexus has been reviewed elsewhere.I~ With the present case included, 61 cases have been reported as carcinoma of the choroid plexus since the initial mention of it as a rarity by Rokitansky 3~in 1844 (Table 1). Whether or not the neoplasm is termed a " p r i m a r y choroid plexus carcinoma" depends upon the criteria used. The strictest criteria are those of Russell and Rubinstein 31 and Lewis, 23 and are as follows: 1) invasion of the adjacent neural tissue with infiltrating cells that assume a diffuse growth pattern; 3~ 2) loss of the regular papillary structure of the neoplasm, at least where invasion is occurring, and obvious malignant alterations in the cells; 8~ and 3) transition of normal choroid plexus architecture to an undifferentiated pattern. 23 The neoplasm described in this article was diagnosed as carcinoma of the choroid plexus since it complies with these three criteria. Papillary ependymomas, choroid plexus papillomas, m e t a s t a t i c carcinomas, and "collision tumors" (carcinoma metastatic to a choroid plexus papilloma) should be included in the differential diagnosis of car-
cinoma of the choroid plexus. Papillary ependymomas would have a fibrillary neuroglial stroma and blepharoplasts in the epithelial cells, while choroidal neoplasms would not. sx Papillomas of the choroid plexus would conform to normal choroid plexus architecture and cytology. S u b a r a c h n o i d spread or "seeding" may be noted with either benign or malignant choroidal neoplasms. 28 The most common metastatic carcinoma that might be mistaken for a malignant choroid plexus neoplasm is bronchogenic carcinoma. If there is no reaction on periodic acid-Schiff and mucin staining and a negative chest x-ray film, metastatic bronchogenic carcinoma would tend to be unlikely; however, a very small primary carcinoma in the lung may never be excluded. If massive necrosis is noted, it is usually associated with metastatic papillary adenocarcinoma and is not seen in primary choroidal carcinoma. 47 "Collision tumors" would not have areas of transition from normal choroidal epithelium to an undifferentiated pattern with histological manifestations of malignancy. Twenty-two cases of carcinoma of the choroid plexus, including the present case, have been reported that largely fulfill the previously listed criteria. Sixteen of these occurred in children and six in adults; sex distribution was equal. The mean age of afflicted children was 2.5 years while in adults it was 39 years. Children succumbed from the disease after a shorter course; the time from onset of s y m p t o m s to death was approximately 9 months in children and 3.5 years in adults. All of the choroid plexus carcinomas in children occurred in the lateral ventricles (67% left; 33% right), while most of the tumors in adults were located in the fourth ventricle (Table 2).
TABLE 2
Summary of 22 cases of primary carcinoma of the choroid plexus
Patients
children (16) adults (6) overall (22) 230
Sex (%) M F
Mean Age (yrs)
Time of Onset of Symptoms to Death
42 67 50
2.5 39 12.5
9 mos 3.5 yrs 1.4 yrs
58 33 50
Ventricle Location (%) Rt Lt Lateral Lateral 3rd 4th 33 20 30
67 0 47
0 0 0
0 80 23
J. Neurosurg. / Volume 43 / August, 1975
Choroid plexus carcinoma References 1. Banna M: Angiography of malignant choroid plexus papilloma. Br J Radiol 44:412-415, 1971 2. Berger M: Metastasierendes Papillom des Plexus chorioideus ventriculi IV. Zentralbl AIIg Pathol 80:5-9, 1942 3. Bielsehowsky M, Unger E: Zur Kenntniss der primaren Epithelgeschwiilste der Adergeflechte des Gehirns. Langenbecks Arch Chit 81:61-82, 1906 4. Bohm E, Strung R: Choroid plexus papillomas. J Neurosurg 18:493-500, 1961 5. Boudet G, Clunet J: Contribution h l'6tude des tumeurs 6pith61iales primitives de r6nc6phale. D6velopp6es aux d6pens des formations 6pendymaires et particuli~rement des plexus choroides. Arch M6d Exp 22:379-411, 1910 6. Brochu P, Lefebvre R: Ad6nocarcinome papillaire mucipare multicentrique des plexus choroides. Union M6d Can 100:1787-1789, 1971 7. Cardauns H: Crber ein malignes Plexuspapillom. Zentralbl Neurochir 17:349-353, 1957 8. Dandy WE: Benign, Encapsulated Tumors in the Lateral Ventricles of the Brain. Diagnosis and Treatment. Baltimore, Williams and Wilkins, 1934 9. Davis LE, Cushing H: Papillomas of the choroid plexus. With report of six cases. Arch Neurol Psychiatry 13:681-710, 1925 10. Dohrmann G J: The choroid plexus: a historical review. Brain Res 18:197-218, 1970 11. Dohrmann G J: Dark and light epithelial cells in the choroid plexus of mammals. J Ultrastruct Res 32:268-273, 1970 12. Dohrmann GJ, Bucy PC: Human choroid plexus: a light and electron microscopic study. J Nenrosurg 33:506--516, 1970 13. Dufek H: Zur Frage des prim~iren Carcinoms des Plexus chorioideus. Zentralbi AIIg Pathol 100:136-142, 1959 14. Esser A: Ein Carcinom des Plexus chorioideus des 4 Ventrikels. Z Gesamtel Neurol Psychiatr 106:511-517, 1926 15. Faber V: Fall yon carcinomat5s entartetem Papillom des Seitenventrikels. Frankfurt Z Pathol 47:168-172, 1934 16. Graves GW, Fliess MM: Neoplasm of the choroid plexus. Report of a case with review of the literature. Am J Dis Child 47:97-103, 1934 17. Hall GW, Fentress TL: Papilloma choroideum with diffuse central nervous system metastases. J Neurol Psychopathoi 14:108-115, 1933 18. Hart K: Ueber prim~ire epitheliale Geschw[iiste des Gehirns; zugleich Untersuchungen und Betrachtungen fiber das Ependymepithel. Arch Psyehiatr Nervenkr 47: 739-773, 1910
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19. K~51pin O: Multiple Papillome (AdenoCarcinome) des Gehirns. Arch Psychiatr Nervenkr 45:595-604, 1909
20. Kono N: Ober Implantatinsmetastasen im Subarachnoidalraum, zugleich ein Beitrag zur Frage der LiquorstriSmung. Frankfurt Z Pathol 30:92-103, 1924 21. KSrner H: Geschw~ilste der Adergeflechte. Zentralbl AIIg Pathol 30:121-135, 1919 22. Lehoczky von T: Zur Frage der prim~iren Gehirncarcinome. Arch Psychiatr Nervenkr 82:527-566, 1928 23. Lewis P: Carcinoma of the choroid plexus. Brain 90:177-186, 1967 24. Lindenberg R: Ober ein Plexusepitheliom des 3 Ventrikels mit geschichtetem Plattenepithel und einer Auskleidung der Ventrikelwand mit dem gleichen Epithel. Zentralbi Alig Pathol 88:47-51, 1951 25. Loginov EN: (Primary cancer of the choroid plexus in a child). Arkh Patol 22:63-65, 1960
(Rus)
26. Matson DD, Crofton FDL: Papilloma of the choroid plexus in childhood. J Neuroserg 17:1002-1027, 1960 27. Mussaelian SK: (On the diffuse malignant epitheliome of the vascular plexus). Neuropatoi Pslkh 9:77-80, 1940 (Rus) 28. Noodt K: Ein Beitrag zur Kenntnis der papill~iren Epitheliome des Plexus chorioideus. Virchows Arch (Pathol Anat) 258:331-336, 1925 29. Ringertz N, Reymond A: Ependymomas and choroid plexus papillomas. J Neuropathol Exp Neurol 8:355-380, 1949 30. Rokitansky C: Handbuch der speciellen pathologischen Anatomic. Vol 1. Vienna, Braumiiller and Seidel, 1844 31. Russell DS, Rubinstein L J: Pathology of Turnouts of the Nervous System. ed 2. London, E Arnold, 1971 32. Saxer F: Ependymepithel, Gliome und epitheliale Geschwiilste des Centralnervensystems. Beitr Pathol 32:276-350, 1902 33. Shuangshoti S, Tangchai P, Netsky MG: Primary adenocarcinoma of the choroid plexus. Arch Pathol 91:101-106, 1971 34. Spaet F: Prim~irer multipler Epithelkrebs des Gehirns. Aertzl Int-BI 30:305-307, 1883 35. Tham KT, Wen HL, Teoh TB: A case of papillary adenocarcinoma of the choroid plexus. J Pathol 99:321-324, 1969 36. TiSppich G: Die Zottenkrebse des Adergeflechtes der Rautengrube. Frankfurt Z Pathol 33:238-247, 1925 37. Turner OA, Simon MA: Malignant papillomas of the choroid plexus. Report of two cases with a review of the literature. Am J Cancer 30:289-297, 1937 38. van Bouwdijk Bastiaanse FS: Prim~ires, 231
G. J. Dohrmann and J. C. Collias
39. 40. 41. 42. 43. 44. 45.
232
metastatasierendes Gehirncarcinom. Z Ges Neurol Psychiatr 27:96-108, 1915 van Hoytema G J, Winckel WEF: Zur Frage des prim~iren Plexuskarzinoms. Zentralbl Neurochir 17:353-363, 1957 Vinken P J, Slooff ACJ: A case of carcinoma of the choroid plexus in a child. Zentralbl Neurochir 26:313-317, 1965 Vraa-Jensen G: Papilloma of the choroid plexus with pulmonary metastases. Acta Psychiatr Neuroi 25:299-306, 1950 Walker JC, Horrax G: Papilloma of the choroid plexus. With report of an unusual case. J Neurosurg 4:387-391, 1947 Wilkins H, Smith R, Halpert B: Neoplasm of the choroid plexus of the left lateral ventricle. J Neurosurg 5:406-410, 1948 Zand N, Mackiewitz J: Papillome malin du plexus choroide. Eneephale 24:841-845, 1929 Zander E: 6 F/ille yon Papillomen des Plexus
chorioideus. Monatschr Psychiatr Neurol 118:321-363, 1949 46. Zdrahal N: Ein Fall yon Karzinom des Plexus chorioideus mit ungewohnlichen klinischen Erscheinungen. Arch Kinderhlkd 109:24-29, 1936 47. Ziilch KJ: Brain Tumors: Their Biology and Pathology, ed 2. New York, Springer-Verlag, 1965
This work was supported in part by Grant NS 10174 from the National Institute of Neurological Diseases and Stroke. Address reprint requests to: George J. Dohrmann, M.D., Ph.D., Sections of Neurosurgery and Neuropathology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510.
J. Neurosurg. / Volume 43 / August, 1975
