Granular Cell Astrocytoma

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TABLE OF CONTENTS

[CLINICAL=20 FEATURES] [HISTOPATHOLOGY]=20 [CYTOCHEMISTRY=20 AND...] [ELECTRON=20 MICROSCOPY] [DIFFERENTIAL=20 DIAGNOSIS] [HISTOGENESIS]=20 [REFERENCES]=20 [FIGURES]

=A9=20 Copyright by College of American Pathologists 2008=20

Archives of Pathology and Laboratory = Medicine:=20 Vol. 132, No. 12, pp. 1946=961950.

Granular Cell Astrocytoma

Yan Shi, MD, PhD; Nora Morgenstern, MD

From the Department of Pathology, Long Island Jewish Medical = Center,=20 New Hyde Park, NY

Accepted April 9, 2008

Granular=20 cell astrocytoma (GCA) is a rare type of malignant brain tumor with = distinct=20 morphologic features and aggressive clinical behavior. Almost all = GCAs occur=20 in the cerebral hemispheres. It is characterized by a prominent = component of=20 bland-looking granular cells. The tumor cells are usually positive = for glial=20 fibrillary acidic protein, S100, CD68, and epithelial membrane = antigen. The=20 most important differential diagnoses include a number of reactive = lesions=20 such as cerebral infarction, multiple sclerosis, and progressive = multifocal=20 leukoencephalopathy. Electron microscopic study reveals that the = granules of=20 GCA correspond to an increased number of intracytoplasmic lysosomes. = The=20 histogenesis of GCA is still unclear, but most people believe it = originates=20 from astrocytes. Loss of 9p and 10q were identified in almost all = cases of=20 GCA, but they are not specific for this tumor. Surgical excision = plus=20 postoperative chemotherapy or radiotherapy is the choice for most = patients=20 with GCA.

3D"" Granular cell astrocytoma (GCA), which has also = been called=20 intracerebral granular cell tumor or astrocytoma with granular = cell=20 differentiation, is a rare type of infiltrative malignant brain = tumor. It=20 was first described by Markesbery et al^{1<=
/SUP>=20
in 1973 as granular cell tumor in the central nervous system. =
Later, GCA=20
was found to be a highly aggressive neoplasm, in dramatic contrast to =
the benign=20
nature of =93granular cell tumors=94 in other parts of the body. =
Furthermore, most=20
reported GCAs were positive for glial fibrillary acidic protein (GFAP).=20
Therefore, it is considered a rare variant of glial neoplasm with =
remarkable=20
granular cell changes.^{2<=
/SUP>=20
Approximately 50 cases have been reported in the literature. Most of =
them were=20
presented as case reports. The first large series of GCA was published =
by Geddes=20
et al^{3<=
/SUP>=20
in 1996 describing 5 cases of astrocytoma composed either entirely or=20
predominantly of granular cells. Later, in 2002 Brat et al^{2<=
/SUP>=20
investigated histopathologic features, grading, and outcome of 22 cases =
and=20
started to use the name granular cell astrocytoma.}}}}

CLINICAL FEATURES Return=20 to TOC

3D"" Based on the literature reports, the ages of the = patients=20 range from 25 to 79 years. The mean age is 55 years. The male-female = ratio is=20 2:1.^2=96=
4=20 Patients usually present with headache, vomiting, newly onset seizures, = aphasia,=20 hemiparesis, blurred vision, and confusion. Almost all GCAs occur in the = cerebral hemispheres.^2=96=
4=20 Only one case was reported in the cerebellum.^{5<=
/SUP>=20
Most recently, Baena et al^{6<=
/SUP>=20
documented 1 case of GCA in the spinal cord. The most common locations =
are the=20
frontal, parietal, and temporal lobes. Brat et al^{2<=
/SUP>=20
reported that 36% of GCAs were located in the frontal lobe, 27% in the =
parietal=20
lobe, 27% in the temporal lobes, and 9% in the occipital lobe. =
Occasionally, GCA=20
can occur in the corpus callosum, basal ganglia, and pineal region.^2=96=
4=20
Computed tomography scan and magnetic resonance imaging studies usually =
reveal=20
GCA as a solid or cystic cerebral tumor with pronounced mass effect (Figure=
=20
1, A ).}}}

HISTOPATHOLOGY Return=20 to TOC

3D"" The most distinctive morphologic feature of GCA = is its=20 prominent component of granular cells^2=96=
4=20 (Figure= =20 1, B 3D""=20 ). These = tumor cells=20 are large with distinct cell borders. They are round to oval in shape = and=20 characterized by abundant eosinophilic granular cytoplasm. Some tumor = cells=20 display a clear central cytoplasmic area and the granules accumulate at = the=20 periphery beneath the cell membrane (Figure= =20 1, C 3D""=20 ). The = nuclei of these=20 granular cells are bland, round to oval, varied in size, and often = eccentrically=20 located. Occasionally, single small nucleoli can be observed. = Lymphocytic=20 infiltration, especially perivascular lymphocytic cuffing, is often = noticed (Figure= =20 1, D 3D""=20 ).^2=96=
4=20 Tumors can be entirely composed of granular cells, but more often = granular cells=20 coexist with conventional infiltrating astrocytoma. Brat et al^{2<=
/SUP>=20
reported that among 22 cases of GCA they investigated, 73% (16/22) =
contained=20
areas of conventional astrocytoma.}

CYTOCHEMISTRY AND IMMUNOHISTOCHEMISTRY Return=20 to TOC

3D"" The cytoplasmic granules of this tumor are = periodic=20 acid=96Schiff positive and diastase resistant.^2=96=
4=20 Immunohistochemical studies show that most GCAs are positive for GFAP.^2=96=
5=20 The cytoplasmic GFAP staining can be presented in a uniform pattern or = with a=20 targetoid appearance (central clearing).^2,=^{3<=
/SUP>=20
However, Brat et al^{2<=
/SUP>=20
found that GFAP immunostaining in GCA was generally low (<30%), and =
in some=20
cases it was focal and patchy. Negative GFAP immunostaining was reported =
in a=20
few articles.^7,=^8<=
/SUP>}}

3D"" Granular cell astrocytoma is positive for CD68, = epithelial=20 membrane antigen (EMA), and S100 (Figure= =20 2, A through C 3D""=20 ).^2=96=
4=20 CD68 is a 110-kd lysosomal glycoprotein highly expressed by monocytes = and=20 macrophages.^{9<=
/SUP>=20
Although it is used as a characteristic marker for histiocytic =
differentiation,=20
the expression of CD68 has been identified in a number of tumors =
including=20
melanoma, leiomyosarcoma, and pleomorphic xanthoastrocytoma.^9=96=
11=20
Conventional astrocytomas were rarely reported to express CD68. Leenstra =
et al^1=
2=20
found 6 well-characterized astrocytoma cell lines expressing a panel of=20
macrophage markers including CD68. The significance of this finding is =
not=20
clear. They proposed that the expression of macrophage phenotype may =
promote=20
tumor growth through elevated production of growth factors and =
angiogenic=20
factors.^1=
2=20
In EMA-positive cells, immunoreactivity is either uniform throughout the =

cytoplasm or accumulated at the cell periphery, which is consistent with =
the=20
distribution of the cytoplasmic granules observed on =
hematoxylin-eosin=96 stained=20
slides. No true membrane staining is present. Ki-67 usually is negative =
or very=20
low in GCA (Figure=
=20
2, D ). The MIB-1 =
index was=20
reported to range from 1.1% to 2.9% in 1 study^1=
3=20
and 0.5% to 15% in another.^1=
4=20
The low MIB-1 index suggests that the granular cells of GCA are =
senescent cells=20
and the granules may represent degenerative changes of astrocytes.^1=
3=20
Bcl-2 was found to be negative in GCA.^1=
3=20
However, only 3 cases have been investigated. Granular cell astrocytoma =
is also=20
reported to be positive for the protein degradation marker ubiquitin, =
lysosomal=20
membrane glycoproteins LAMP-1 and LAMP-2.^2,=^3<=
/SUP>}

ELECTRON MICROSCOPY Return=20 to TOC

3D"" Ultrastructural studies demonstrate that GCA = contains large=20 numbers of autophagic lysosomes in the form of dense bodies, = multivesicular=20 bodies, and vacuoles. The lysosomes are distributed at the periphery of = the=20 cytoplasm corresponding to the distribution of the granules observed on=20 hematoxylin-eosin=96stained slides.^2=96=
4=20 It is believed that the granules of GCA correspond to an increased = number of=20 intracytoplasmic lysosomes, which also provide the structural basis for = positive=20 CD68 expression observed in GCA. Various amounts of intermediate = filaments can=20 also be observed in GCA tumor cells. They are often located at the = periphery of=20 the cells.^2=96=
4=20 By contrast, conventional astrocytoma contains only scattered lysosomes = but=20 innumerable intermediate filaments.^1=
5

DIFFERENTIAL DIAGNOSIS Return=20 to TOC

3D"" Histologically, the granular tumor cells can be = confused with=20 macrophages. Therefore, it is important to differentiate GCA from a = number of=20 reactive lesions such as cerebral infarction, multiple sclerosis, and=20 progressive multifocal leukoencephalopathy. Helpful features for the=20 differential diagnosis include the following: (1) GCA tumor cells = display at=20 least some cellular polymorphism and atypia. The tumor cells vary in = size and=20 shape with occasional small nucleoli. In addition, granular tumor cells = ranging=20 in size from 60 to 100 μm in diameter are often significantly = larger than=20 macrophages.^{2<=
/SUP>=20
Unlike macrophages, granular cells of GCA display a central clear =
cytoplasmic=20
area with the granules accumulating at the periphery of the cell, under =
the cell=20
membrane. (2) GCA tumor cells are positive for GFAP, which is usually =
negative=20
in macrophages. However, because GFAP immunostaining in GCA can be focal =
and=20
weak or even negative,^{2<=
/SUP>=20
GFAP staining is not always helpful in establishing the diagnosis. =
Positive GFAP=20
can confirm the diagnosis of GCA, but negative staining should not =
exclude the=20
diagnosis of GCA, especially when the sample size is small. (3) GCA may =
be=20
associated with the conventional type of astrocytoma.^2=96=
4=20
Brat et al^{2<=
/SUP>=20
reported that among 22 cases of GCA they studied, 16 (73%) cases were =
mixed with=20
conventional astrocytoma. Geddes et al^{3<=
/SUP>=20
found that 15 of 27 cases of GCA reported in the literature were =
associated with=20
anaplastic astrocytes. However, conventional infiltrating astrocytoma =
may not=20
always be present, especially in small biopsies. (4) Macrophages, the =
mimicker=20
of GCA, can be observed in cerebral infarct, but it is usually =
accompanied by=20
eosinophilia of neurons (=93red neuron=94) and neutrophil infiltration. =
Red neurons=20
are not reported in GCA. (5) Multiple sclerosis is an =
autoimmune-mediated=20
demyelinating disorder located in white matter. Even though it can =
present with=20
abundant macrophages and perivascular lymphocytic cuffs, the lesions are =

characterized by multiple well-demarcated demyelinated plaques different =
from=20
the diffuse infiltrative growth pattern of GCA. (6) Progressive multiple =

leukoencephalopathy is a viral encephalitis involving the white matter. =
It=20
usually affects immunocompromised patients and is caused by JC =
polyomavirus. The=20
lesions are characterized by irregular, ill-defined patches of =
demyelination,=20
lipid-laden macrophages, and reduced numbers of axons. The most =
important=20
diagnostic feature of progressive multifocal leukoencephalopathy is the =
presence=20
of greatly enlarged oligodendrocytes with glassy amphophilic =
intranuclear viral=20
inclusions. (7) Clinical history can be helpful in the differential =
diagnosis=20
because clinical presentations are different among these diseases. =
Cerebral=20
infarct tends to happen abruptly within hours. Granular cell astrocytoma =
may=20
take several weeks or months to develop. Multiple sclerosis and =
progressive=20
multifocal leukoencephalopathy usually manifest as chronic diseases with =
long=20
clinical courses.}}}}

3D"" It is also important to differentiate GCA from = granular cell=20 tumor of the neurohypophysis or infundibulum, which is a benign primary = tumor=20 located intrasellarly and/or suprasellarly.^1=
1=20 This tumor is histologically very similar to GCA and characterized by = nests of=20 large polygonal cells with abundant granular cytoplasm and sometimes = spindle=20 cells. Variable expression of GFAP protein has been described in a = subset of=20 granular cell tumors of the neurohypophysis.^1=
0=20 The tumor cells are positive for periodic acid=96Schiff stain, = neuron-specific=20 enolase, α₁-antitrypsin, and = α₁-chymotrypsin.^1=
1=20 More importantly, granular cell tumor of the neurohypophysis is a = benign, slowly=20 progressive tumor without invasive growth pattern.

3D"" Pituicytoma used to be regarded as a synonym of = granular cell=20 tumor of the neurohypophysis,^1=
1=20 but this is a misnomer. In 2000, Brat et al^1=
6=20 studied a series of 9 cases of pituicytoma and clarified the definition = of this=20 tumor. Pituicytoma is a rare low-grade glioma of the sellar and = suprasellar=20 region, which is thought to originate from pituicytes, a specialized = glial cell,=20 of the stalk and posterior lobe of the pituitary gland. The tumor is=20 histologically different from GCA and characterized by elongated, = bipolar=20 spindle cells arranged in interlacing fascicles and/or storiform growth = pattern.=20 The tumor cells contain oval to elongated nuclei, small inconspicuous = nucleoli,=20 and eosinophilic, slightly fibrillary cytoplasm, without granularity or=20 vacuolization. Periodic acid=96Schiff stain is rarely positive in = pituicytoma.^1=
6,^1=
7=20 Imaging study usually reveals a well-circumscribed solid mass located in = the=20 sellar or suprasellar region. Therefore, morphologically and clinically, = pituicytoma is distinct from GCA and granular cell tumor of the = neurohypophysis=20 and should be regarded as a different disease entity.

HISTOGENESIS Return=20 to TOC

3D"" The histogenesis of GCA is still unclear, but = most people=20 favor its astrocyte origin because of the positive GFAP immunostaining = and its=20 coexistence with conventional astrocytoma in a substantial portion of = reported=20 cases.^2=96=
4=20 Melaragno et al^{4<=
/SUP>=20
demonstrated that the soft tissue form of granular cell tumor is =
negative for=20
GFAP and EMA immunostaining. This result indicates that GCA and granular =
cell=20
tumor have different cell origins, which may be the reason for their =
different=20
biologic behaviors. It is unclear if GCA is truly an entity in its own =
right or=20
simply prominent degenerative change with lysosomal accumulation in =
varying=20
proportions of tumor cells. Kornfeld^1=
8=20
proposed that granular cells were transformed neoplastic astrocytes that =

developed from the cells containing abundant cytoplasmic intermediate =
filaments=20
and a few granules to the ones containing less or no cytoplasmic =
intermediate=20
filaments and abundant granules. This hypothesis provides an explanation =
for the=20
=93transitional areas=94 observed in some cases in which GCA is admixed =
with=20
conventional astrocytoma.}

3D"" Interestingly, most GCA cases reported in the = literature=20 displayed strong cytoplasmic immunostaining for EMA (Figure= =20 2, B 3D""=20 ). = Epithelial membrane=20 antigen is a monoclonal antibody prepared initially against breast = epithelial=20 cell membranes. It is considered to be an epithelial marker, but the = staining=20 can be seen in many other cells and tumors such as plasma cells, = monocytes,=20 meningioma, synovial sarcoma, and anaplastic large cell lymphoma. = Although=20 Geddes et al considered this type of EMA staining to be nonspecific = because it=20 was cytoplasmic instead of membranous staining, there were different = opinions=20 concerning a potential epithelial differentiation derived from = astrocytoma.^1=
9=20 Further studies are needed to determine the histogenesis of GCA and the=20 significance of EMA staining.

Grading

3D"" In 2 studies, GCA was diagnosed when the tumor = had at least=20 more than 30% granular cells.^2,=^2=
0=20 Granular cell astrocytoma was graded based on the criteria for = astrocytoma of=20 the 2000 World Health Organization. Grade 2 was defined as tumors with=20 occasional nuclear atypia and absence of mitosis. However, finding a = rare=20 mitosis does not upgrade the tumor to anaplastic astrocytoma. Grade 3 = was=20 defined as tumors with hypercellularity, distinct nuclear atypia, and = marked=20 mitotic activity. Grade 4 was defined as tumors with pseudopalisading = necrosis=20 and/or endothelial hyperplasia.^2,=^2=
1,^2=
2

Genetic Alterations

3D"" No genetic alterations were found to be specific = for GCA.=20 Castellano-Sanchez et al^2=
0=20 found that GCA displayed higher frequencies of loss of heterozygosity at = 1p, 9p,=20 10q, 17p, and 19q than conventional infiltrating astrocytomas of similar = grades.=20 Loss of 9p and 10q were identified in almost all cases, including = low-grade=20 lesions. TP53 mutations, p14 and p16 combined deletions were = observed in=20 some high-grade GCA tumors. Epidermal growth factor receptor = amplification is a=20 common event in high-grade astrocytoma, but it was not identified in a = small=20 series of GCA.^2=
0=20 Further studies are needed to investigate the genetic alterations of = GCA.

Treatment and Prognosis

3D"" Surgical removal plus postoperative chemotherapy = or=20 radiotherapy is the choice for most patients with GCA. However, because = of its=20 aggressive clinical behavior, most patients with GCA die within 1 = year.^{2<=
/SUP>=20
Compared with conventional astrocytoma, the prognosis of GCA is much =
worse.=20
According to Brat et al,^{2<=
/SUP>=20
the average survival of patients with grade 3 and 4 conventional =
astrocytoma was=20
3 years and 11 months, respectively. In contrast, the average survival =
of=20
patients with grades 3 and 4 GCA was 8.4 and 7.3 months, respectively. =
It is=20
unclear why GCA behaves in such an aggressive manner despite its low =
mitotic=20
rate and MIB-1 index. Castellano-Sanchez et al^2=
0=20
found that GCA displayed a higher frequency of loss of heterozygosity at =
9p and=20
10q than the conventional astrocytoma of similar grade, which may =
contribute to=20
its aggressive clinical behavior.}}

References Return=20 to TOC

1. Markesbery WR, = Duffy PE,=20 Cowan D. Granular cell tumors of the central nervous system. J = Neuropathol=20 Exp Neurol 1973;32:92=96109.

2. Brat DJ, Scheithauer BW,=20 Medina-Flores R, Rosenblum MK, Burger PC. Infiltrative astrocytomas with = granular cell features (granular cell astrocytomas): a study of = histopathologic=20 features, grading, and outcome. Am J Surg Pathol = 2002;26:750=96757.=20

3. Geddes JF, Thom = M,=20 Robinson S, Revesz T. Granular cell change in astrocytic tumors. Am J = Surg=20 Pathol 1996;20:55=9663.

4. Melaragno MJ, Prayson RA, = Murphy MA,=20 Hassenbusch SJ, Estes ML. Anaplastic astrocytoma with granular cell=20 differentiation: case report and review of the literature. Hum = Pathol=20 1993;24:805=96808.

5. Saad A,=20 Mo J, Miles L, Witte D. Granular cell astrocytoma of the cerebellum: = report of=20 the first case. Am J Clin Pathol 2006;126:602=96607.

6. Baena RR, DiIeva A, Colombo = P. et al.=20 Intramedullary astrocytoma with granular cell differentiation. = Neurosurg=20 Rev 2007;30:339=96343.

7. Claassen U, Kuntz G, = Schmitt HP.=20 Malignant intracerebral granular cell tumor reacts positively with=20 anti-alpha-1-antichymotrypsin and the MB2 antibody: a clue to the = histogenesis=20 of the brain granular cell?. Clin Neuropathol 1990;9:82=9688. =

8. Gambini C, Ruelle A, = Palladino M,=20 Boccardo M. Intracerebral granular cell tumor. Pathologica = 1990;82:83=9688.=20

9. Weiss LM, Arber = DA, Chang=20 KL. CD68: a review. Appl Immunohistochem 1994;2:2=968.

10. McHugh M, Miettinen M. = KP1 (CD68):=20 its limited specificity for histiocytic tumors. Appl = Immunohistochem=20 1994;2:186=96190.

11. Warzok=20 RW, Vogelgesang S, Feiden W, Shuangshoti S. Granular cell tumor of=20 neurohypophysis. In: Kleihues P, Cavenee WK, eds. Pathology and = Genetics of=20 Tumors of the Nervous System. 2nd ed. Lyon, France: IARC Press;=20 2000:247=96248. World Health Organization Classification of = Tumours.=20

12. Leenstra S, = Das PK,=20 Troost K, de Boer OJ, Bosch DA. Human malignant astrocytes express = macrophage=20 phenotype. J Neuroimmunol 1995;56:17=9625.

13. Chorny JA, Evans LC,=20 Kleinschmidt-Demasters BK. Cerebral granular cell astrocytomas: a Mib-1, = bcl-2=20 and telomerase study. Clin Neuropathol 2000;19:170=96179. =

14. Rickert CH, Kuchelmeister = K,=20 Gullotta F. Morphological and immunohistochemical characterization of = granular=20 cells in non-hypophyseal tumours of the central nervous system.=20 Histopathology 1997;30:464=96471.

15. Dickersin GR. Central = nervous=20 system neoplasms. In: Dickersin GR, ed. Diagnostic Electron = Microscopy: A=20 Text/Atlas. 2nd ed. New York, NY: Springer-Verlag New York Inc; = 1999:499.=20

16. Brat DJ, = Scheithauer BW,=20 Staugaitis SM, Holtzman RN, Morgello S, Burger PC. Pituicytoma: a = distinctive=20 low-grade glioma of the neurohypophysis. Am J Surg Pathol=20 2000;24:362=96368.

17. Schultz=20 AB, Brat DJ, Oyesiku NM, Hunter SB. Intrasellar pituicytoma in a patient = with=20 other endocrine neoplasms. Arch Pathol Lab Med = 2001;125:527=96530.=20

18. Kornfeld M. = Granular=20 cell glioblastoma: a malignant granular cell neoplasm of astrocytic = origin. J=20 Neuropathol Exp Neurol 1986;45:447=96462.

19. Gosgrove M, Fitzgibbons = PL, Sherrod=20 A, Chandrasoma PT, Matin SE. Intermediate filament expression in = astrocytic=20 neoplasms. Am J Surg Pathol 1989;13:141=96145.

20. Castellano-Sanchez AA, = Ohgaki H,=20 Yokoo H. et al. Granular cell astrocytomas show a high frequency of = allelic loss=20 but are not a genetically defined subset. Brain Pathol = 2003;13:185=96194.=20

21. von Deimling = A, Burger=20 PC, Nakazato Y, Ohgaki H, Kleihues P. Diffuse astrocytoma. In: Louis DN, = Ohgaki=20 H, Wiestler OD, Cavenee WK, eds. WHO Classification of Tumours of the = Central=20 Nervous System. 3rd ed. Lyon, France: IARC Press; 2007:25=9629. =

22. Kleihues P, Burger PC, = Rosenblum=20 MK, Paulus W, Scheithauer BW. Anaplastic astrocytoma. In: Louis DN, = Ohgaki H,=20 Wiestler OD, Cavenee WK, eds. WHO Classification of Tumours of the = Central=20 Nervous System. 3rd ed. Lyon, France: IARC Press; 2007:30=9632. =

Figures Return=20 to TOC

Click on thumbnail for full-sized = image.

3D""=20 Figure 1. 3D""=20 A,=20 Axial magnetic resonance imaging shows a solid/cystic mass of granular = cell=20 astrocytoma in the frontal lobe. B, Neoplastic cells of granular cell=20 astrocytoma are characterized by abundant eosinophilic granular = cytoplasm and=20 eccentrically located nuclei (hematoxylin-eosin, original magnification = =D7100).=20 C, Neoplastic cells of granular cell astrocytoma display a targetoid = appearance=20 with a clear central area (hematoxylin-eosin, original magnification = =D7400). D,=20 Perivascular lymphocytic cuffing is often noticed (hematoxylin-eosin, = original=20 magnification =D7400)

Click on thumbnail for full-sized = image.

3D""=20 Figure 2. 3D""=20 A,=20 CD68 cytoplasmic positivity in granular cell astrocytoma (original = magnification=20 =D7200). B, Epithelial membrane antigen cytoplasmic positivity in = granular cell=20 astrocytoma (original magnification =D7200). C, Positive S100 stain in = granular=20 cell astrocytoma (original magnification =D7200). D, MIB-1 expression is = low in=20 granular cell astrocytoma. Note: positive staining observed in a = reactive=20 astrocyte (original magnification = =D7200)

The authors have no relevant financial interest in the = products or=20 companies described in this article.

Reprints: Nora Morgenstern, = MD, Department=20 of Pathology, Long Island Jewish Medical Center, 270-05 76th Ave CH036, = New Hyde=20 Park, NY 11040 (E-mail: nmorgens@lij.edu)

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