An Unusual Nodular Tumour of the Penile Shaft with Clinicopathologic and Immunohistochemical Correlation
Poonam Abhay ELHENCE1, Deepak VEDANT1, Saurabh SINGH2, Puneet PAREEK3
1Department of Pathology and Lab Medicine, All India Institute of Medical Sciences, JODHPUR, INDIA
2Department of Dermatology, Venereology and Leprology, All India Institute of Medical Sciences, JODHPUR, INDIA
3Department of Radiation Oncology, All India Institute of Medical Sciences, JODHPUR, INDIA
Keywords: Penis, Granular cell tumour, Benign, Immunohistochemistry
Granular cell tumours are uncommon acquired benign tumours of nerve sheath origin that are usually seen in the head and neck region and
upper aero-digestive tract. They usually present as solitary small sized nodules in middle age. The tumour is usually benign and composed of
sheets of large sized cells with abundant granular cytoplasm containing lysosomal macro-inclusions known as pustulo-ovoid bodies of Milian
(POB) that represent the heterogeneity of the lysosomes. No well-established criteria for malignancy have been described for this tumour. In this
article, we have discussed a rare case of granular cell tumour of the penis with its characteristic histomorphology and immunohistochemistry
and relevant differential diagnosis.
Granular cell tumour is an uncommon, benign tumour
of nerve sheath origin. Most are acquired and present as
a solitary skin-coloured nodule, less than 2 cm in size 1
Usually, these tumours are seen in middle age. The most
common locations are the upper aerodigestive tract, and in
the skin and subcutaneous tissue. Granular cell tumour of
the penis is very rare. In this article, we report the case of a
granular cell tumour of the penis with a clinical suspicion
of an indurated epidermal inclusion cyst.
A 49-year-old immunocompetent male presented with the
complaint of a single, non-itchy nodule on the shaft of the
penis for one month. On clinical evaluation, the nodule was
on the shaft of the penis, 1.5 cm in diameter and firm with
no ulceration. No definite punctum was visible. There was
no discharge from the lesion or penile urethra. No inguinal
lymph nodes were palpable. The patient did not have any
history of sexual exposure. No comorbidities were present.
Excision of the nodule was done with the clinical diagnosis
of epidermal inclusion cyst and sent for histopathological
examination. A clinical photograph of the lesion was not
taken at that time as the clinical suspicion was that of
an indurated epidermal inclusion cyst and a diagnosis
of granular cell tumour was not considered prior to the
excision of nodule.
Microscopic examination of 5 um Hematoxylin and Eosin
(H&E)-stained sections showed unremarkable mucosal
epithelium. The subepithelial connective tissue showed
an unencapsulated tumour comprised of sheets of large,
polygonal cells with a central vesicular nucleus, variably
conspicuous nucleoli, and abundant coarsely granular
eosinophilic cytoplasm (Figure 1). Large cytoplasmic
granules, surrounded by a clear halo (pustulo-ovoid
bodies of Milian), were frequently seen (Figure 2). The
tumour cells were surrounding an occasional peripheral
small nerve. No high nuclear-cytoplasmic ratio, significant
pleomorphism, spindling, necrosis, apoptosis, or mitoses
were evident. Immunohistochemical stains for S100P,
Inhibin, CD68, SMA, Myogenin, HMB45, GFAP, and Bcl2
were carried out. On immunohistochemistry, the tumour
cells showed diffuse positivity for S100 protein (Figure 3A),
and CD68 (Figure 3B); focal positivity for Inhibin (Figure
3C), and Bcl2 (Figure 3D); and were negative for SMA,
Myogenin, HMB45, and GFAP. A diagnosis of benign
granular cell tumour of the penile shaft was made. The
patient was completely asymptomatic after surgery and had
an uneventful recovery. He has been on follow up for three
years with no evidence of recurrence.
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|Figure 1: Microphotograph showing penile epithelium with
subepithelial tumour in sheets (H&E; x100)
Click Here to Zoom
|Figure 2: Microphotograph showing large cytoplasmic granules,
surrounded by a clear halo (pustulo-ovoid bodies of Milian)
Click Here to Zoom
|Figure 3: A) Microphotograph showing immunohistochemistry for A) S100P exhibiting diffuse immune-positivity (IHC; x100).
B) CD68 exhibiting diffuse immune-positivity (IHC; x100). C) Inhibin-alpha with focal immune-positivity (IHC; x400).
D) Bcl-2 exhibiting diffuse immune-positivity (IHC; x400).
Granular cell tumour or Abrikossoff tumour is an
uncommon, benign tumour of nerve sheath origin. Most
tumours are acquired and present as solitary skin-coloured
nodules, less than 2 cm in size 1
. About 10% are seen as multiple lesions 2
. Usually, these tumours are seen in
middle age. The most common locations are the upper
aerodigestive tract, and in the skin and subcutaneous tissue
. Granular cell tumour of the penis is very rare 3,4
Similar tumours called congenital epulis are seen on the
anterior alveolar ridge in neonates 5.
The overlying epithelium often shows pseudo-epitheliomatous
hyperplasia, which may be misdiagnosed as squamous
cell carcinoma. Often, small nerves are seen in and around
the tumour. Abundant granular cytoplasm is present.
The cytoplasmic lysosomal macro-inclusions or pustuloovoid
bodies of Milian (POB) are an easily recognizable
component of granular cell tumour and they appear to
represent the heterogeneity of the lysosomes, giving the
appearance of large granules that have partially detached
from the adjacent cytoplasm 6.
No well-established criteria for malignancy have been
described for this tumour. However, tumour size greater
than 5 cm, vascular invasion, necrosis, increased mitosis,
apoptotic cells, cell spindling and rapid growth have been
reported in malignant lesions 7.
Histologically, these tumours need to be differentiated from
melanocytic neoplasms, leiomyosarcoma, atypical fibroxanthoma,
dermatofibroma with granular cell change, and
adult-type rhabdomyoma. Absence of melanin pigment
or any epithelial component, and negative HMB45 helped
to rule out melanocytic neoplasms. Leiomyosarcoma with
an epithelioid morphology show necrosis, atypical mitosis,
and epithelioid cell morphology, and stain on immunohistochemistry
for SMA and Myogenin which are negative in
granular cell tumours. Dermatofibroma usually have an
admixture of fibroblastic, myofibroblastic, and histiocytic
cells with a storiform pattern with inflammatory cells, foam
cells, and giant cells. Some of them may demonstrate granular
cell change. On immunohistochemistry, the dermatofibromas
are negative for S100P.
Adult-type rhabdomyoma has typical histological finding
of large polyhedral cells with abundant eosinophilic
and granular cytoplasm. Cross striations may be
appreciated and these tumours are positive for SMA,
Desmin, and Myogenin, and are negative for S100P on
Immunohistochemical studies favour a Schwann cell origin.
On immunohistochemical examination, granular cell
tumours usually express S100 protein, CD68, microphthalmia
transcription factor (MITF), inhibin-α, and NSE 8.
This case highlights an uncommon soft tissue tumour of the
penis with uncertain histogenesis proposed to have a neural origin that can clinically mimic an epidermal inclusion cyst
and other entities. Most of the granular cell tumours are
benign and solitary, and occur in the head and neck region
in middle age. They may mimic malignancy clinically.
Characteristic abundant cytoplasm, low-grade nuclear
features, and cytoplasmic lysosomal macro-inclusions
(POB of Milian) with relevant immunohistochemistry
help to diagnose these unusual neoplasms. These tumours
are treated by surgical excision and rarely recur. The
knowledge about the occurrence of this rare tumour at an
unusual site should be borne in mind and confirmed by
relevant immunohistochemical stains that help to establish
the diagnosis and rule out other mimics.
CONFLICT of INTEREST
The authors declare no conflict of interest.
Concept: PAE, Design: PP, SS, Data collection or processing:
PAE, Analysis or Interpretation: DV, PAE, Literature
search: PAE, SS, DV, Writing: PAE, DV, Approval: PAE,
DV, SS, PP.
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