Germ Cell Tumors Masquerading Nervous System Sarcoidosis David M.
Central
Peeples, MD; Barney J. Stern, MD; Violet Jiji, MD; K. Singh Sahni, MD
\s=b\ The diagnosis of central nervous system sarcoidosis is uncertain without typical multisystem involvement. We describe two patients with isolated central nervous system mass lesions whose biopsy results were consistent with sarcoidosis. After a progressive clinical course, they were found to have diencephalic germinomas. Germ cell tumors, in particular, should be considered in the differential diagnosis of central nervous system sarcoidosis as they are potentially treatable, occur in intracranial locations favored by sarcoidosis mass lesions, and may be surrounded by granulomatous inflammation that can be mistaken for the noncaseating granulomas of sarcoidosis. (Arch Neurol. 1991 ;48:554-556)
Tntracranial granulomatous mass le¬ sions can arise from diverse path¬
ogenic mechanisms. Infectious process¬ es, inflammatory disorders, and neo¬ plastic disease can all result in granulo¬ matous reactions. Sarcoidosis can pre¬ sent with isolated central nervous sys¬
tem (CNS) involvement,1 occasionally in the form of a mass lesion2; systemic manifestations are typically found or
Accepted for publication November 7,1990. From the Department of Neurology, The Johns Hopkins Medical Institutions, Baltimore, Md (Drs Peeples and Stern); the Division of Neurology (Dr Stern) and the Department of Pathology (Dr Jiji), Sinai Hospital of Baltimore (Md); and the Department of Neurosurgery, Medical College of Virginia, Richmond (Dr K. Singh Sahni). Reprint requests to Division of Neurology, Sinai Hospital of Baltimore, Baltimore, MD 21215 (Dr Stern).
as
develop over time. We describe two pa¬ tients with diencephalic granulomatous mass lesions that were initially thought to represent CNS sarcoidosis, but were found, after relentless progression, to
be germ cell tumors.
REPORT OF CASES
CASE 1.—A 37-year-old white man pre¬ sented in October 1985 with polyuria and polydipsia. Evaluation revealed a partial antidiuretic hormone deficiency, positive pu¬ rified protein derivative tuberculin, and a 2.5-cm suprasellar contrast-enhancing mass on computed tomographic scan. A chest roentgenogram revealed old granulomas. Results of lacrimal gland biopsy and angiotensin-converting enzyme levels were nor¬ mal, as were serum and cerebrospinal fluid ß-human chorionic gonadotrophin and a-fetoprotein levels. A stereotactic biopsy specimen showed a mononuclear cell infil¬ trate consistent with granulomatous disease. The patient was treated with desmopressin acetate (dDAVP), isoniazid, and rifampin. In October 1986, diminished visual acuity oc¬ curred, and computed tomographic scans re¬ vealed a slight increase in the size of the lesion (Fig 1, left). The diagnosis of sarcoid¬ osis was made, and prednisone therapy (80 mg/d) was initiated. In December 1986,
.the patient developed headaches,
a
post-
syndrome with a right homony¬ mous hemianopsia and a left inferior quadrantanopsia, and tinnitus and hearing loss in the right ear. His cerebrospinal fluid was acellular (protein, 0.96 g/L; and glucose, 3.2 mmol/L). He underwent surgical exploration in January 1987; the mass had a friable ap¬ pearance and was adherent to the hypothala¬ mus. Pathologic examination revealed in¬ flammatory cells with a granulomatous chiasmatic
reaction consistent with sarcoidosis. Acidfast bacilli and fungal stains and cultures were negative. Prednisone therapy (140 mg/d) improved the patient's visual and aural symptoms, but by April 1987 he again devel¬ oped progressive visual loss and constricted visual fields. Complete réévaluation for sys¬ temic sarcoidosis was negative, and in May 1987 cyclosporine was administered in addi¬ tion to prednisone as part of an investigational study for refractory neurosarcoidosis. In July 1987 the findings ofthe patient's neuro¬ logic examination were unchanged, but a computed tomographic scan of his cranium revealed further enlargement of the mass (Fig 1, right). He developed Pneumocystis carinii pneumonia and died after a respira¬
tory arrest.
Autopsy revealed a 5.5 2.0 1.1-cm pedunculated mass composed of gray, some¬ what rubbery tissue protruding from the sella turcica, involving both optic nerves, the optic chiasm, and the pituitary stalk, and loosely adherent to the base ofthe third ven¬ tricle and hypothalamus. Microscopic exami¬ nation revealed a germinoma composed of sheets of large round cells with pale cyto¬ plasm and hyperchromatic nuclei. Lymphoid cells were infiltrating between the tumor cells and fibrovascular stroma. No granulo¬ mas were seen (Fig 2). The eighth cranial nerves were normal. CASE 2.—A 16-year-old white boy pre¬ sented in January 1987 with headaches, pap¬ illedema, and a small enhancing lesion ob¬ structing the foramen of Monroe (Fig 3, left). Ventriculoperitoneal shunting was followed by a right frontal craniotomy and a biopsy, which revealed a granulomatous reaction in the floor of the third and left lateral ventri¬ cles, consistent with sarcoidosis (Fig 4, left). There was no tumor found, and acid-fast ba¬ cilli, fungal, and mucin stains were negative. Analysis of cerebrospinal fluid showed 8
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Fig 1. —Left, Contrast-enhanced computed tomographic scan of patient 1 reveals a discrete suprasellar mass. Right, Contrast-enhanced computed tomographic scan of the same patient 9 months later shows enlargement of the mass.
Fig 2. —Representative histologie section of the germinoma obtained at autopsy of patient 1 reveals characteristic germinoma cells in a loose vascular stroma with interspersed lym¬ phocytes (hematoxylin-eosin,
320).
monocytes; protein, 0.34 g/L; and glucose, 4.3 mmol/L; the cytopathologic findings were negative. Systemic evaluation for sarcoid¬ osis was unrevealing. Prednisone therapy (40 mg/d) was initiated. In July 1987 a com¬ puted tomographic scan revealed extensive enhancement in the anterior third ventricle and hypothalamus. The patient developed mild central hypopituitarism, with slightly low thyrotropin, thyroxine, and testosterone levels. Weekly infusions of methylpredniso¬ lone (30 mg/kg) were begun, but by Septem¬ ber 1987 there was a 3-cm intraventrieular
enhancing mass (Fig 3, right), and a hypotha¬ syndrome with hyperpyrexia, hypersomnolence, and diabetes insipidus had developed. In October 1987 a large heteroge¬ lamic
neous
third ventricular
mass was
removed.
Pathologic examination revealed malignant germinoma, composed predominantly of em¬ bryonal carcinoma and focal teratoma (Fig 4, right). There was extensive necrosis and granulomatous inflammation. An immunoperoxidase a-fetoprotein stain was positive. Postoperatively, the patient did poorly, with rapid tumor recurrence despite radiation therapy and chemotherapy. He died of sepsis
Fig 3. —Left, Contrast-enhanced computed tomographic scan of patient 2 reveals an enhancing lesion near the third ventricle and dilatation of the left lateral ventricle. Right, Contrast-enhanced computed tomographic scan of the same patient 8 months later reveals a large cystic mass.
several months later.
COMMENT
Sarcoidosis is a multisystem granulo¬ matous disease of unknown origin with manifestations in 5% of neurologic '•:u cases. Nearly 50% of patients with neurosarcoidosis will have neurologic symptoms as the initial feature of their illness. Although rare, isolated granulo¬ matous mass lesions can be the sole clin¬ ical manifestation of sarcoidosis.2 The suprasellar region is a characteristic site, and diabetes insipidus, as in our first patient, is not an unusual presenta¬ tion.'' Nevertheless, multisystem in-
volvement is the rule: one autopsy study found disseminated disease to be com¬ mon despite isolated neurologic symp¬ toms," and another clinical series of 50 consecutive patients with neurosarcoidosis reported that of 24 who pre¬ sented with neurologic symptoms, sys¬ temic involvement eventually devel¬ oped in all but five. ' Both our patients were white males who lacked the stigmata of multisystem sarcoidosis such as elevated serum angiotensin-converting enzyme levels, adenopathy, uveitis, or pulmonary inflam-
mation. Neurosarcoidosis was enter¬ tained on the basis of biopsy ofthe CNS lesion, twice in our first patient, which revealed no evidence of neoplasia or in¬ fection. Although a granulomatous CNS mass lesion could be either true isolated CNS sarcoidosis or simply a harbinger of systemic involvement, the lack of evidence for multisystem sar¬ coidosis makes a diagnosis, even on the basis of biopsy, far less certain. Fur¬ thermore, concurrent corticosteroid treatment can make detection of inflam¬ mation in other organs difficult.
Downloaded From: http://archneur.jamanetwork.com/ by a GLASGOW UNIVERSITY LIBRARY User on 05/20/2015
sarcoidosis on the biopsy specimen of a lesion demonstrating noncaseating granulomas is fraught with uncer¬ tainty. Our two cases illustrate several important aspects in the management of patients with granulomatous mass le¬ sions from presumed isolated CNS sar¬ coidosis: (1) The diagnosis of CNS sar¬ coidosis is most certain if multisystem disease is demonstrated. (2) Biopsy of a mass lesion can miss the primary patho¬ logic process and reveal only a nonspe¬ cific granulomatous reaction. (3) If clinical progression occurs, with en¬ largement ofthe mass lesion despite ag¬ gressive corticosteroid therapy, contin¬ ued search for systemic disease and another biopsy, if possible, are indi¬ cated to rule out infection or neoplasia. (4) Corticosteroid therapy may mask the stigmata of disease at other sites. (5) Germ cell tumors, in particular, need to be considered because they are po¬ mass
Fig 4. —Left, Section of open biopsy specimen from patient 2 reveals granulomatous inflammation (hematoxylin-eosin, 320). Right, Second biopsy specimen obtained 8 months later shows a malignant germ cell tumor with features of an embryonal carcinoma (hematoxylin-eosin, 320).
Although noncaseating granulomas the pathologic hallmark of sarcoi¬ dosis, granulomatous inflammation is nonspecific and must be considered are
within the clinical framework. Granulo¬ formation can arise from diverse processes including tuberculosis, atypi¬ cal mycobacteria, fungal infections,
ma
syphilis, brucellosis, actinomycosis, tu¬ laremia, leprosy, vasculitis, and foreign body reactions and as a response to cer¬ tain neoplasms. Histologically, the sar¬ coidosis granuloma is composed of large pale-pink epithelial cells with inter¬ spersed giant cells and lymphocytes. Caseation is not prominent, but may
and cause confusion with tubercu¬ losis. Schaumann's and asteroid bodies are perhaps most common in sarcoidosis granulomas, but they are not pathognomonic features and cannot be reliably used as diagnostic criteria. The treatment of CNS sarcoidosis mass lesions typically begins with corti¬ costeroid therapy. In refractory cases, or when decompensation is imminent owing to mass effect, high-dose cortico¬ steroid therapy, treatment with other occur
'
immunosuppressive agents, surgical exploration, and radiotherapy are often considered.' These interventions
can
lead to further diagnostic confusion. For instance, lymphoma may respond to corticosteroid or radiation therapy. The possibility of alternative diagnoses should always be kept in mind and aggressively excluded. Intracranial germ cell tumors, also called atypical teratoma or ectopie pin-
occasionally
ealoma, are rare.8 They usually occur in pineal region, causing increased in¬
the
tracranial pressure and Parinaud's ophthalmoplegia. A suprasellar location is the second most common site. Diabe¬ tes insipidus can be an early sign, with the late development of hypopituitarism, hypothalamic dysfunction, visual field defects, and raised intracranial pressure. Symptoms and sites of in¬ volvement are strikingly similar to sar¬ coidosis mass lesions. Furthermore, a granulomatous reaction is common in the periphery of such lesions, and the malignancy can be missed on biopsy if the core of the tumor is not obtained.H Some germinomas secrete a-fetoprotein, ß-human chorionic gonadotrophin, or placental alkaline phospha¬ tase.1" An elevated cerebrospinal fluid angiotensin-converting enzyme level has been documented in a patient with a suprasellar germinoma," a finding that can occur in CNS sarcoidosis and there¬ contribute to diagnostic con¬ by further fusion. 12 One of our patients had no tu¬ mor markers at presentation, and the other was not evaluated prior to tumor debulking, at which time the tissue had a
positive a-fetoprotein immunoperoxi-
dase stain. It is possible that if elevated cerebrospinal fluid levels of a-fetopro¬ tein had been detected, an earlier diag¬ nosis might have been possible. There is an excellent response of germ cell tu¬ mors
to
radiotherapy,"1314 highlighting
the importance of accurate diagnosis. Without the stigmata of multisystem disease, basing the diagnosis of CNS
tentially treatable, frequently occur at intracranial locations favored by sar¬ coidosis, and have a prominent sur¬ rounding granulomatous reaction. Richard J. Otenasek, Jr, MD. referred patient 2. We thank Ed Koo, MD, who reviewed the patholo¬ gy specimens, and Gwendolyn Boyd and Charlie Harper, who helped prepare the manuscript.
References 1. Oksanen V. Neurosarcoidosis: clinical presentations and course in 50 patients. Acta Neurol Scand. 1986;73:283-290. 2. Norwood CW, Kelly DL. Intracerebral sarcoidosis acting as a mass lesion. Surg Neurol.
1974;2:367-372.
3. Delaney P. Neurologic manifestations in sarcoidosis: review of the literature with a report of 23 cases. Ann Intern Med. 1977;87:336-345. 4. Stern BJ, Krumholz A, Johns CJ. Neurosarcoidosis: presentation and management. Ann N Y Acad Sci. 1986;465:722-730. 5. Pennell WH. Boeck's sarcoid with involvement of the central nervous system. Arch Neurol
Psychiatry. 1951;66:728-737.
6. Gailloud C, Rabinowicz T. Sarcoidose et sysneuveux central. Doc Ophthalmol. 1969;25: 248-281. 7. Robbins SL, Cotran RS. Infectious diseases. In: Pathologic Basis of Disease. Philadelphia, Pa: WB Saunders Co; 1979:477-478. 8. Takeuchi J, Handa H, Nagata I. Suprasellar germinoma. J Neurosurg. 1978;49:41-48. 9. Kaspar C, Schneider N, Childers J, Wilson J. Suprasellar germinoma: unresolved problems in diagnosis, pathogenesis, and management. Am J Med. 1983;75:705-711. 10. Javadpour N. The role of biologic tumor markers in testicular carcinoma. Cancer. 1980; 45:1755-1761. 11. Rohmer V, Saint-Andre JP, Alhenc-Gelar F, Corvol P, Bigorgne J. Angiotensin I converting enzyme in a suprasellar germinoma. Am J Clin Pathol. 1987;87:281-284. 12. Oksanen V, Fyhrquist F, Somer H, Gronhagen-Riska C. Angiotensin converting enzyme in cerebrospinal fluid: a new assay. Neurology. teme
1985;35:1220-1223.
13. Fields J, Fulling K, Thomas P, Marks J. Suprasellar germinoma: radiation therapy. Radiol-
ogy. 1987;164:247-249. 14. Sung D, Harisiadis L, Chang C. Midline pineal tumors and suprasellar germinoma: highly cur-
able by irradiation.
Downloaded From: http://archneur.jamanetwork.com/ by a GLASGOW UNIVERSITY LIBRARY User on 05/20/2015
Radiology. 1978;128:745-751.
Central
Peeples, MD; Barney J. Stern, MD; Violet Jiji, MD; K. Singh Sahni, MD
\s=b\ The diagnosis of central nervous system sarcoidosis is uncertain without typical multisystem involvement. We describe two patients with isolated central nervous system mass lesions whose biopsy results were consistent with sarcoidosis. After a progressive clinical course, they were found to have diencephalic germinomas. Germ cell tumors, in particular, should be considered in the differential diagnosis of central nervous system sarcoidosis as they are potentially treatable, occur in intracranial locations favored by sarcoidosis mass lesions, and may be surrounded by granulomatous inflammation that can be mistaken for the noncaseating granulomas of sarcoidosis. (Arch Neurol. 1991 ;48:554-556)
Tntracranial granulomatous mass le¬ sions can arise from diverse path¬
ogenic mechanisms. Infectious process¬ es, inflammatory disorders, and neo¬ plastic disease can all result in granulo¬ matous reactions. Sarcoidosis can pre¬ sent with isolated central nervous sys¬
tem (CNS) involvement,1 occasionally in the form of a mass lesion2; systemic manifestations are typically found or
Accepted for publication November 7,1990. From the Department of Neurology, The Johns Hopkins Medical Institutions, Baltimore, Md (Drs Peeples and Stern); the Division of Neurology (Dr Stern) and the Department of Pathology (Dr Jiji), Sinai Hospital of Baltimore (Md); and the Department of Neurosurgery, Medical College of Virginia, Richmond (Dr K. Singh Sahni). Reprint requests to Division of Neurology, Sinai Hospital of Baltimore, Baltimore, MD 21215 (Dr Stern).
as
develop over time. We describe two pa¬ tients with diencephalic granulomatous mass lesions that were initially thought to represent CNS sarcoidosis, but were found, after relentless progression, to
be germ cell tumors.
REPORT OF CASES
CASE 1.—A 37-year-old white man pre¬ sented in October 1985 with polyuria and polydipsia. Evaluation revealed a partial antidiuretic hormone deficiency, positive pu¬ rified protein derivative tuberculin, and a 2.5-cm suprasellar contrast-enhancing mass on computed tomographic scan. A chest roentgenogram revealed old granulomas. Results of lacrimal gland biopsy and angiotensin-converting enzyme levels were nor¬ mal, as were serum and cerebrospinal fluid ß-human chorionic gonadotrophin and a-fetoprotein levels. A stereotactic biopsy specimen showed a mononuclear cell infil¬ trate consistent with granulomatous disease. The patient was treated with desmopressin acetate (dDAVP), isoniazid, and rifampin. In October 1986, diminished visual acuity oc¬ curred, and computed tomographic scans re¬ vealed a slight increase in the size of the lesion (Fig 1, left). The diagnosis of sarcoid¬ osis was made, and prednisone therapy (80 mg/d) was initiated. In December 1986,
.the patient developed headaches,
a
post-
syndrome with a right homony¬ mous hemianopsia and a left inferior quadrantanopsia, and tinnitus and hearing loss in the right ear. His cerebrospinal fluid was acellular (protein, 0.96 g/L; and glucose, 3.2 mmol/L). He underwent surgical exploration in January 1987; the mass had a friable ap¬ pearance and was adherent to the hypothala¬ mus. Pathologic examination revealed in¬ flammatory cells with a granulomatous chiasmatic
reaction consistent with sarcoidosis. Acidfast bacilli and fungal stains and cultures were negative. Prednisone therapy (140 mg/d) improved the patient's visual and aural symptoms, but by April 1987 he again devel¬ oped progressive visual loss and constricted visual fields. Complete réévaluation for sys¬ temic sarcoidosis was negative, and in May 1987 cyclosporine was administered in addi¬ tion to prednisone as part of an investigational study for refractory neurosarcoidosis. In July 1987 the findings ofthe patient's neuro¬ logic examination were unchanged, but a computed tomographic scan of his cranium revealed further enlargement of the mass (Fig 1, right). He developed Pneumocystis carinii pneumonia and died after a respira¬
tory arrest.
Autopsy revealed a 5.5 2.0 1.1-cm pedunculated mass composed of gray, some¬ what rubbery tissue protruding from the sella turcica, involving both optic nerves, the optic chiasm, and the pituitary stalk, and loosely adherent to the base ofthe third ven¬ tricle and hypothalamus. Microscopic exami¬ nation revealed a germinoma composed of sheets of large round cells with pale cyto¬ plasm and hyperchromatic nuclei. Lymphoid cells were infiltrating between the tumor cells and fibrovascular stroma. No granulo¬ mas were seen (Fig 2). The eighth cranial nerves were normal. CASE 2.—A 16-year-old white boy pre¬ sented in January 1987 with headaches, pap¬ illedema, and a small enhancing lesion ob¬ structing the foramen of Monroe (Fig 3, left). Ventriculoperitoneal shunting was followed by a right frontal craniotomy and a biopsy, which revealed a granulomatous reaction in the floor of the third and left lateral ventri¬ cles, consistent with sarcoidosis (Fig 4, left). There was no tumor found, and acid-fast ba¬ cilli, fungal, and mucin stains were negative. Analysis of cerebrospinal fluid showed 8
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Fig 1. —Left, Contrast-enhanced computed tomographic scan of patient 1 reveals a discrete suprasellar mass. Right, Contrast-enhanced computed tomographic scan of the same patient 9 months later shows enlargement of the mass.
Fig 2. —Representative histologie section of the germinoma obtained at autopsy of patient 1 reveals characteristic germinoma cells in a loose vascular stroma with interspersed lym¬ phocytes (hematoxylin-eosin,
320).
monocytes; protein, 0.34 g/L; and glucose, 4.3 mmol/L; the cytopathologic findings were negative. Systemic evaluation for sarcoid¬ osis was unrevealing. Prednisone therapy (40 mg/d) was initiated. In July 1987 a com¬ puted tomographic scan revealed extensive enhancement in the anterior third ventricle and hypothalamus. The patient developed mild central hypopituitarism, with slightly low thyrotropin, thyroxine, and testosterone levels. Weekly infusions of methylpredniso¬ lone (30 mg/kg) were begun, but by Septem¬ ber 1987 there was a 3-cm intraventrieular
enhancing mass (Fig 3, right), and a hypotha¬ syndrome with hyperpyrexia, hypersomnolence, and diabetes insipidus had developed. In October 1987 a large heteroge¬ lamic
neous
third ventricular
mass was
removed.
Pathologic examination revealed malignant germinoma, composed predominantly of em¬ bryonal carcinoma and focal teratoma (Fig 4, right). There was extensive necrosis and granulomatous inflammation. An immunoperoxidase a-fetoprotein stain was positive. Postoperatively, the patient did poorly, with rapid tumor recurrence despite radiation therapy and chemotherapy. He died of sepsis
Fig 3. —Left, Contrast-enhanced computed tomographic scan of patient 2 reveals an enhancing lesion near the third ventricle and dilatation of the left lateral ventricle. Right, Contrast-enhanced computed tomographic scan of the same patient 8 months later reveals a large cystic mass.
several months later.
COMMENT
Sarcoidosis is a multisystem granulo¬ matous disease of unknown origin with manifestations in 5% of neurologic '•:u cases. Nearly 50% of patients with neurosarcoidosis will have neurologic symptoms as the initial feature of their illness. Although rare, isolated granulo¬ matous mass lesions can be the sole clin¬ ical manifestation of sarcoidosis.2 The suprasellar region is a characteristic site, and diabetes insipidus, as in our first patient, is not an unusual presenta¬ tion.'' Nevertheless, multisystem in-
volvement is the rule: one autopsy study found disseminated disease to be com¬ mon despite isolated neurologic symp¬ toms," and another clinical series of 50 consecutive patients with neurosarcoidosis reported that of 24 who pre¬ sented with neurologic symptoms, sys¬ temic involvement eventually devel¬ oped in all but five. ' Both our patients were white males who lacked the stigmata of multisystem sarcoidosis such as elevated serum angiotensin-converting enzyme levels, adenopathy, uveitis, or pulmonary inflam-
mation. Neurosarcoidosis was enter¬ tained on the basis of biopsy ofthe CNS lesion, twice in our first patient, which revealed no evidence of neoplasia or in¬ fection. Although a granulomatous CNS mass lesion could be either true isolated CNS sarcoidosis or simply a harbinger of systemic involvement, the lack of evidence for multisystem sar¬ coidosis makes a diagnosis, even on the basis of biopsy, far less certain. Fur¬ thermore, concurrent corticosteroid treatment can make detection of inflam¬ mation in other organs difficult.
Downloaded From: http://archneur.jamanetwork.com/ by a GLASGOW UNIVERSITY LIBRARY User on 05/20/2015
sarcoidosis on the biopsy specimen of a lesion demonstrating noncaseating granulomas is fraught with uncer¬ tainty. Our two cases illustrate several important aspects in the management of patients with granulomatous mass le¬ sions from presumed isolated CNS sar¬ coidosis: (1) The diagnosis of CNS sar¬ coidosis is most certain if multisystem disease is demonstrated. (2) Biopsy of a mass lesion can miss the primary patho¬ logic process and reveal only a nonspe¬ cific granulomatous reaction. (3) If clinical progression occurs, with en¬ largement ofthe mass lesion despite ag¬ gressive corticosteroid therapy, contin¬ ued search for systemic disease and another biopsy, if possible, are indi¬ cated to rule out infection or neoplasia. (4) Corticosteroid therapy may mask the stigmata of disease at other sites. (5) Germ cell tumors, in particular, need to be considered because they are po¬ mass
Fig 4. —Left, Section of open biopsy specimen from patient 2 reveals granulomatous inflammation (hematoxylin-eosin, 320). Right, Second biopsy specimen obtained 8 months later shows a malignant germ cell tumor with features of an embryonal carcinoma (hematoxylin-eosin, 320).
Although noncaseating granulomas the pathologic hallmark of sarcoi¬ dosis, granulomatous inflammation is nonspecific and must be considered are
within the clinical framework. Granulo¬ formation can arise from diverse processes including tuberculosis, atypi¬ cal mycobacteria, fungal infections,
ma
syphilis, brucellosis, actinomycosis, tu¬ laremia, leprosy, vasculitis, and foreign body reactions and as a response to cer¬ tain neoplasms. Histologically, the sar¬ coidosis granuloma is composed of large pale-pink epithelial cells with inter¬ spersed giant cells and lymphocytes. Caseation is not prominent, but may
and cause confusion with tubercu¬ losis. Schaumann's and asteroid bodies are perhaps most common in sarcoidosis granulomas, but they are not pathognomonic features and cannot be reliably used as diagnostic criteria. The treatment of CNS sarcoidosis mass lesions typically begins with corti¬ costeroid therapy. In refractory cases, or when decompensation is imminent owing to mass effect, high-dose cortico¬ steroid therapy, treatment with other occur
'
immunosuppressive agents, surgical exploration, and radiotherapy are often considered.' These interventions
can
lead to further diagnostic confusion. For instance, lymphoma may respond to corticosteroid or radiation therapy. The possibility of alternative diagnoses should always be kept in mind and aggressively excluded. Intracranial germ cell tumors, also called atypical teratoma or ectopie pin-
occasionally
ealoma, are rare.8 They usually occur in pineal region, causing increased in¬
the
tracranial pressure and Parinaud's ophthalmoplegia. A suprasellar location is the second most common site. Diabe¬ tes insipidus can be an early sign, with the late development of hypopituitarism, hypothalamic dysfunction, visual field defects, and raised intracranial pressure. Symptoms and sites of in¬ volvement are strikingly similar to sar¬ coidosis mass lesions. Furthermore, a granulomatous reaction is common in the periphery of such lesions, and the malignancy can be missed on biopsy if the core of the tumor is not obtained.H Some germinomas secrete a-fetoprotein, ß-human chorionic gonadotrophin, or placental alkaline phospha¬ tase.1" An elevated cerebrospinal fluid angiotensin-converting enzyme level has been documented in a patient with a suprasellar germinoma," a finding that can occur in CNS sarcoidosis and there¬ contribute to diagnostic con¬ by further fusion. 12 One of our patients had no tu¬ mor markers at presentation, and the other was not evaluated prior to tumor debulking, at which time the tissue had a
positive a-fetoprotein immunoperoxi-
dase stain. It is possible that if elevated cerebrospinal fluid levels of a-fetopro¬ tein had been detected, an earlier diag¬ nosis might have been possible. There is an excellent response of germ cell tu¬ mors
to
radiotherapy,"1314 highlighting
the importance of accurate diagnosis. Without the stigmata of multisystem disease, basing the diagnosis of CNS
tentially treatable, frequently occur at intracranial locations favored by sar¬ coidosis, and have a prominent sur¬ rounding granulomatous reaction. Richard J. Otenasek, Jr, MD. referred patient 2. We thank Ed Koo, MD, who reviewed the patholo¬ gy specimens, and Gwendolyn Boyd and Charlie Harper, who helped prepare the manuscript.
References 1. Oksanen V. Neurosarcoidosis: clinical presentations and course in 50 patients. Acta Neurol Scand. 1986;73:283-290. 2. Norwood CW, Kelly DL. Intracerebral sarcoidosis acting as a mass lesion. Surg Neurol.
1974;2:367-372.
3. Delaney P. Neurologic manifestations in sarcoidosis: review of the literature with a report of 23 cases. Ann Intern Med. 1977;87:336-345. 4. Stern BJ, Krumholz A, Johns CJ. Neurosarcoidosis: presentation and management. Ann N Y Acad Sci. 1986;465:722-730. 5. Pennell WH. Boeck's sarcoid with involvement of the central nervous system. Arch Neurol
Psychiatry. 1951;66:728-737.
6. Gailloud C, Rabinowicz T. Sarcoidose et sysneuveux central. Doc Ophthalmol. 1969;25: 248-281. 7. Robbins SL, Cotran RS. Infectious diseases. In: Pathologic Basis of Disease. Philadelphia, Pa: WB Saunders Co; 1979:477-478. 8. Takeuchi J, Handa H, Nagata I. Suprasellar germinoma. J Neurosurg. 1978;49:41-48. 9. Kaspar C, Schneider N, Childers J, Wilson J. Suprasellar germinoma: unresolved problems in diagnosis, pathogenesis, and management. Am J Med. 1983;75:705-711. 10. Javadpour N. The role of biologic tumor markers in testicular carcinoma. Cancer. 1980; 45:1755-1761. 11. Rohmer V, Saint-Andre JP, Alhenc-Gelar F, Corvol P, Bigorgne J. Angiotensin I converting enzyme in a suprasellar germinoma. Am J Clin Pathol. 1987;87:281-284. 12. Oksanen V, Fyhrquist F, Somer H, Gronhagen-Riska C. Angiotensin converting enzyme in cerebrospinal fluid: a new assay. Neurology. teme
1985;35:1220-1223.
13. Fields J, Fulling K, Thomas P, Marks J. Suprasellar germinoma: radiation therapy. Radiol-
ogy. 1987;164:247-249. 14. Sung D, Harisiadis L, Chang C. Midline pineal tumors and suprasellar germinoma: highly cur-
able by irradiation.
Downloaded From: http://archneur.jamanetwork.com/ by a GLASGOW UNIVERSITY LIBRARY User on 05/20/2015
Radiology. 1978;128:745-751.
