Transcript Diapositiva 1

Granular Cell Tumor: when should it
be considered malignant?
Immunohistochemical study of three
cases
S.A. Senatore*, G.A. Colucci*, T.G. Carlà*, F. Floccari*,
A.T. Pede*, E. Villani*, A. D’Amuri*°
* U.O.C. Anatomia Patologica Ospedale “S. Cuore di Gesù” P.O. Gallipoli
ASL/LE
° Dipartimento di Patologia Umana ed Oncologia Sez. Anatomia
Patologica Università degli Studi di Siena
INTRODUCTION
 Granular Cell Tumor (GCT) is a rare neoplasm which
tends to occur throughout the dermis or subcutis with a
predilection for the head and neck regions, soft tissue and
mucosa of the aerodigestive tracts.
 Visceral involvement is less frequent.
 GCT are accepted as being of neural origin from the
Schwann-cell owing to their peculiar ultrastructural
features and immunohistochemical reactivity with S100
protein, neuron-specific enolase (NSE) and myelin–
specific protein.
 Malignant variants represent only 1% of all cases.
INTRODUCTION
 Clinical manifestations are varied. Many present as pale
white/yellow subcutaneous circumscribed nodules with a
normal or thickened overlying skin.
 The nodules can also be itchy or painful.
 GCT may affect people of a wide age range with a peak of
incidence in the 4th through 6th decades of life.
 The only cure is local surgical excision of benign GCT
while en bloc excision is recommended for malignant
lesions which are not sensitive to radiation and
chemotherapy.
CASE REPORTS
 CASE 1: A 39-year-old white man presented to the ORL
Division for a dysphonia due to a small nodule of the
larynx which was subsequently surgically treated.
 CASE 2: A 50-year-old white woman underwent clinical
evaluation in the Surgical Division for the presence of a
non-ulcerated nodule on the anterior dorsal surface of the
tongue which was surgically excised.
 CASE 3: A 76-year-old white man presented to the
Surgical Division for the evaluation of a nodular lesion
located beneath the surface epithelium of his back.
Because of the suspicion of a melanoma, he was referred
to a surgical management.
SURGICAL FEATURES
 CASE 1: The observed specimen consisted of numerous
fragments. The estimated size of the biggest one was of
1,3 x 0,8 cm and had a whitish appearance.
 CASE 2: The lesion consisted in a whitish fragment of 1,3
x 0,8 cm.
 CASE 3: Grossly, the excised specimen consisted of a
yellowish lozenged-shaped cutis of 3 x 1,4 cm. The
nodular lesion had a maximum diameter of 1,2 cm.
MATERIALS & METHODS
 Specimens were fixed in 10% buffered formalin and
paraffin embedded. 5m serial sections were obtained and
routinely stained with hematoxylin-eosin (H/E) and PAS
histochemical reaction.
 Immunohistochemical studies were performed for Alpha 1
AT, CD68, Citokeratin AE1/AE3, HMB45, Ki-67, Lysozyme,
NSE, S100 protein and Vimentin.
H/E
S100
NSE
Ki-67
MICROSCOPICAL
FINDINGS: CASE 1
 The H/E stained section revealed a nodular neoformation
constituted by typical granular cells showing vescicolous
nuclei with an optically empty appearance cytoplasm.
 Immunohistochemical stains for S100, NSE, CD68,
Vimentin and a1AT were found positive. On the contrary
Ki-67 had a very low proliferative index (≥ 2%).
 A diagnosis of GCT was performed.
S100
Ki-67
NSE
MICROSCOPICAL
FINDINGS: CASE 2
 The histological examination revealed a subepidermical
pseudo-nodular neoformation constituted by typical
granular cells showing vescicolous nuclei with abundant
cytoplasm. Morphological atypia was also noted.
 Immunohistochemical stains for S100, NSE, CD68,
Vimentin and a1AT were found positive. Ki-67 had a low
proliferative index (≤ 5%).
 The O.M. diagnosis of GCT was made and later confirmed
by TEM evaluation.
H/E
S100
NSE
Ki-67
MICROSCOPICAL
FINDINGS: CASE 3
 The H/E stained section demonstrated a subepidermical
nodular cutaneous formation extended to medium derma,
formed by atypical pleomorphic elements showing
vescicolous nuclei, nucleolated with high mitotic index, an
eosinophilic granular cytoplasm, sometimes microvacuolar
with an optically empty appearance.
 Immunohistochemical stains for Vimentin, S100, NSE,
a1AT, CD68 were strong and diffusely positive. Ki-67 had
a high proliferative index (> 50%).
 The reported morphofunctional observations gave
evidence for a malignant cutaneous tumor with
pleomorphic granular elements (MGpCT).
DISCUSSION
 The neoplasms observed are of Schwann cell origin and
our diagnosis is based on their histological features and
immunohistochemical reactivity with S100 protein and
NSE. Ki-67 can predict the clinical behaviour and, as
reported in previous studies, a rare immunostaining was
found in the benign form of GCT (as showed in our 1st and
2nd cases).
 The distinction between benign and malignant GCT is
controversal because of histological similarities. By
convention, GCT are classified as malignant when the
constituent cells show cytological features of malignancy
or when a morphologically benign GCT metastasizes to
regional lymph nodes or distance sites or otherwise
causes death.
DISCUSSION
 The histological criteria for a malignant classification are
based on the presence of necrosis, spindling of tumor
cells, vescicular nuclei with large nucleoli, increased
mitotic activity, high nuclear to cytoplasmic ratio and
pleomorphism. Neoplasms that meet three or more of
these criteria can be classified as histologically malignant.
Our 3th case completely satisfies the reported criteria.
 Our results could also suggest that, in the absence of
“strictly malignant” morphological criteria, the diagnostic
immunealgorithm has no prognostic relevance.
 Finally in the 3th cases observed, in which Ki-67 presents
an increased proliferative index, might be able to define a
high malignant potential GCT.
REFERENCES
1.
Fanburg-Smith J.C. et al. Malignant granular
cell tumor of soft tissue: diagnostic criteria
and clinicopathologic correlation. A J Surg
Pathol 1998, 22 (7): 779-794.
2.
Miracco C. et al. Granular cell tumor with
histological signs of malignancy: report of a
case and comparison with 10 benign and 4
atypical cases. Br J Dermathol 1999, 141 (3):
573-575.
3.
Le B.H. et al. Granular cell tumor
immunohistochemical
assessment
of
inhibin-a protein gene product 9.5, S100
protein, CD68 and Ki-67 proliferative index
with clinical correlation. Arch Pathol Lab Med
2004, 128: 771-775.