Malignant Melanoma Presenting as a Mediastinal Malignant Melanoma Presenting as a Mediastinal Unknown Primary Origin?
Mukta PUJANI1, Mohd Jaseem HASSAN1, Sujata JETLEY1, Prabhat Kumar RAINA2, Mukesh KUMAR3
1Department of Pathology, Hamdard Institute of Medical Sciences & Research, NEW DELHI, INDIA
2Department of Surgery, Hamdard Institute of Medical Sciences & Research, NEW DELHI, INDIA
3Department of Radiology, Hamdard Institute of Medical Sciences & Research, NEW DELHI, INDIA
Keywords: Malignant melanoma, Neoplasm of unknown primary, Mediastinal neoplasm
The most common site of primary malignant melanoma is the skin,
however, virtually any organ system may be involved. Metastatic
melanoma of unknown primary origin accounts for approximately
2-6% of all melanoma cases. The mediastinum as the site for malignant
melanoma is extremely rare, both as a primary or metastatic lesion.
Primary malignant melanoma of mediastinum is very rare with only
a handful of reports in the literature. We hereby report a rare case
of malignant melanoma of mediastinum in a 31 year old male who
was initially misdiagnosed on fine needle aspiration cytology as
adenocarcinoma for which he received chemotherapy with clinical
deterioration. Even on extensive meticulous search, no primary was
Primary Malignant melanoma (MM), although
predominantly a tumor of skin, can occur at almost any
site in the body where nevus cells/ melanocytes are found.
Moreover, MM has a very high tendency for metastasis.
Metastatic melanoma of unknown primary origin (MUP)
accounts for approximately 2-6% of all melanoma cases1
Mediastinum as the site for MM is extremely rare, both as
a primary or a metastatic lesion. On search of literature,
we came across a limited number of reports of mediastinal
. To label a melanoma as MUP,
thorough history, physical examination and extensive
investigative workup is required to exclude a primary MM.
We hereby report a rare case of MM of mediastinum in a
31-year-old male in whom no primary was discovered even
after meticulous search.
A 31-year-old male presented with dry cough and chest
pain associated with weight loss. Six months back the
patient was investigated for similar complaints and a right
parahilar mass measuring 8x6cm was detected in the
anterior mediastinum. Computed tomography guided fine
needle aspiration cytology (FNAC) performed at a private
centre was suggestive of adenocarcinoma. The patient was
given 6 cycles of chemotherapy (paclitaxel and carboplatin)
but did not show any symptomatic improvement and then
presented to our hospital.
On examination, the patient was of average build with no
lymphadenopathy, pallor, icterus or cyanosis. A contrastenhanced
computed tomography (CECT) of the thorax and
abdomen was performed and revealed a large, irregular,
heterogeneously-enhancing soft tissue density mass lesion in the anterior mediastinum, predominantly on the right
side. The lesion measured 10.7 x 9.9 x 10.7 cm and showed
necrotic areas with few foci of calcification with extension
from the level of the arch of aorta superiorly to the level
of the diaphragm (Figure 1). The rest of the visceral
organs were unremarkable. Levels of tumor markers like
carcinoembryonic antigen, CA 19.9, alphafetoprotein and
beta-human chorionic gonadotrophin were within the
normal range. A Tru-cut biopsy was performed from the
Click Here to Zoom
|Figure 1: Chest CT revealed a large, irregular heterogeneouslyenhancing
soft tissue density mass lesion in the anterior
mediastinum, predominantly on right side.
Microscopically, the tumor was composed of round to oval
cells with moderate amount of cytoplasm with melanin
pigment in many cells. Nuclei were moderately pleomorphic
with coarse chromatin and inconspicuous nucleoli (Figure
2). Mitotic rate was 5-6/10 high power fields. Focal areas
of necrosis were also observed. Possibility of malignant
melanoma was suggested. Immunohistochemistry revealed
positive immunostaining for vimentin, HMB-45, S-100
while negative results were obtained with cytokeratin
and CD 45. Neuroendocrine markers like neuron specific
enolase (NSE) and chromogranin were also negative. A
final diagnosis of malignant melanoma was established.
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|Figure 2: Photomicrograph showing
round to oval tumor cells with
moderate amount of cytoplasm
with melanin pigment in many
and moderately pleomorphic
nuclei with coarse chromatin
(H&E; x400); inset top left
immunohistochemistry for HMB
45 was positive, inset bottom left
immunohistochemistry for S-100
A meticulous search for primary was conducted through
examination of the entire skin, eye, genitalia and anal canal.
There was no history of any prior surgical resection of a mole.
Chest X-ray and thoracic and abdominal CECT did not reveal
any lesion in any of the visceral organs. Upper gastrointestinal
tract endoscopy and rectosigmoidoscopy were also performed
and were within normal limits. A diagnosis of melanoma of
unknown primary was therefore established.
The mass was large and unamenable to surgical resection.
The option of chemotherapy was not explored as the
patient had not responded to chemotherapy given prior
to biopsy and MM is not a chemosensitive disorder. The
patient was put on immunotherapy with close follow-up.
CT scan performed three months later showed a large
space-occupying lesion in the liver. The patient expired one
Malignant melanoma accounts for 1.5% of all cancers
with increasing prevalence over the last decade. The most
common site of primary MM is the skin but virtually
any organ system where melanocytes/nevus cells may be
encountered can become involved. Although primary MM
has been reported in the bronchus, brain, gastrointestinal
tract and rectum, melanomas at sites other than skin are
usually secondary deposits. This is due to a high tendency
of melanomas to metastasize3
The mediastinum as a site for malignant melanoma is
extremely unusual either as a metastatic deposit or as
a primary. Primary MM of the mediastinum is very
rare with only a handful of reports in the literature2-6. The differential diagnoses for melanotic tumors
of the mediastinum include pigmented extra adrenal
paraganglioma, pigmented carcinoid tumor of thymus,
melanotic schwannoma, melanotic neuroectodermal
neoplasm and primary MM5. Melanotic
schwannoma and MM can not be distinguished even on
immunohistochemistry as both are strongly positive for
S-100, HMB-45 and melan A. The light microscopic features
favouring melanotic schwannoma include circumscription
without encapsulation, high cellularity, a predominance of
spindle cells, which are heavily pigmented and arranged
in whorls or palisades and a lack of cytological atypia or
mitoses, contrary to the findings in the present case7.
The diagnosis of pigmented extra adrenal paraganglioma
is supported by an organoid or zellballen pattern and
positivity for S-100, NSE, chromogranin and synaptophysin.
Absence of these features helped in ruling out this entity
in our case. Melanotic neuroectodermal neoplasm is
characterised by an admixture of large melanocyte like
cells and smaller neuroblast like cells, infrequent mitoses
and positivity for cytokeratin, NSE, HMB-45 and S-100 on
When the site of origin of a histologically documented
carcinoma is not identified clinically, this is referred to as
carcinoma of unknown primary origin or occult primary
malignancy. The majority of cases of carcinoma of unknown
primary are adenocarcinomas or undifferentiated tumors;
less commonly, squamous cell carcinoma, melanoma,
sarcoma, and neuroendocrine tumors are seen. In
approximately 15% to 25% of patients, the primary site
cannot be identified even at postmortem examination8.
Metastatic melanoma arising from unknown primary origin
was first described in 19529. MUP accounts for 2-6% of all
melanomas. These may be seen as subcutaneous nodules or
lymph node metastases. Very rarely, simultaneous visceral
metastasis may be detected at diagnosis1.
MUP can be explained by the following hypothesis:
1- De novo melanoma can originate from malignant
transformation of ectopic melanocytes/ nevus cells;
2- Complete regression of the primary melanoma after
metastasis has taken place10.
MUP were extensively studied for the first time by Das Gupta
et al.11 in 47 patients from a total of 992 melanoma cases
(3.7%). They laid down certain criteria for the diagnosis of
MUP: 1- Normal findings on eye, rectum and genital region
examination, 2- the following should be excluded: history
of orbital enucleation, any previous surgery for skin lesions
like nevus etc., especially in a region of skin with drainage
to the involved lymph nodes.
Schlagenhauff et al.1 gave recommendations for initial
staging examinations in patients with MUP. According to
them, initial search for the primary should be restricted to
an inspection of entire skin surface and adjacent mucosa
as well as detailed examination of the areas drained by
involved lymph nodes. Chest X ray / computed tomography
(CT), abdominal ultrasound (USG) / CT, USG of regional
lymph nodes and CT / magnetic resonance imaging (MRI)
of brain were generally recommended in all cases of MUP.
Further specific investigations were indicated depending
upon the location of MUP.
When corresponding stages were compared, the survival of
patients with melanoma of unknown primary was found to
be similar to that of patients with known primary12. On
the contrary, Schlagenhauff et al.1 observed a surprisingly
high 5 year survival rate of 83% in patient with stage IIIa
disease. However, unfavourable prognosis was observed in
patients with stage IV disease and MUP.
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Nonsquamous cell type. Semin Oncol. 1982;9:427-34.
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JE, Lee JE, Mansfield PF, Ross MI. Metastatic melanoma to
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