Keywords
malignant pleural mesothelioma - skeletal muscle metastasis - FDG PET/CT - contrast-enhanced
CT
Introduction
Malignant pleural mesothelioma (MPM) is an aggressive form of malignancy with a poor
prognosis of fewer than 12 months from the time of diagnosis. It originates from mesothelial
cells forming the pleural lining.[1] It is strongly associated with remote asbestos exposure. Histopathologically, MPM
has major three subgroups, epithelioid, the predominant subgroup, less commonly sarcomatoid
and biphasic subtypes.
Dissemination of MPM is generally local and regional lymph nodes are the major metastatic
sites of MPM. Distant metastases are uncommon. However, distant metastases from MPM
are considered more common than previously reported and can involve the liver, spleen,
lung, bone, adrenal, kidney, thyroid, and peritoneum, but more rarely the skeletal
muscle and brain.[2]
[3]
[4]
[5]
Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG
PET/CT) has been increasingly used for the presurgical characterization and staging,
evaluation of the response to treatment, accurate detection of distant metastases,
assessing recurrence, and selecting the site for tissue biopsy of MPM.[6]
[7]
[8]
Here, we report a case of MPM with extensive muscle metastases of various sizes in
various skeletal muscle localizations detected by FDG PET/CT but not seen on diagnostic
contrast-enhanced CT (CECT).
Case Report
A 54-year-old woman was diagnosed with epithelioid MPM 2 years ago and she was treated
with right extrapleural pneumonectomy, hyperthermic intrathoracic chemotherapy, and
radiotherapy. Because of her right-sided chest pain complaint, a control diagnostic
CT scan of the chest, abdomen, and pelvis was obtained. Diffuse irregular pleural
thickening with a focal chest wall invasion in the right hemithorax and two small
pleural thickenings in the left hemithorax were seen on CT images. CT of the abdomen
and pelvis did not show any abnormalities. Two weeks later FDG PET/CT imaging was
performed as part of restaging. PET showed diffuse irregular high FDG uptake in the
recurrent right pleural tumor, more prominent in the mediastinal side with maximum
standardized uptake value (SUVmax) of 13.4, and also two hypermetabolic small foci
in the left pleura, which suggest metastatic disease to the contralateral pleura (SUVmax:
2.7). In addition, PET/CT demonstrated multiple round, ovoid, or elongated hypermetabolic
areas of various sizes in various skeletal muscle localizations, strikingly much more
extensive in both legs, including the left medial pterygoid muscle, paraspinal muscles,
both gluteal muscles, right biceps brachii muscle, and numerous muscles of both thighs
and calves (SUVmax measured between 3.4 and 18.5) ([Fig. 1]). On physical examination, the patient had only a slight swelling with mild pain
in the lower part of the right biceps brachii muscle. Otherwise, she did not have
any abnormal findings related to the skeletal muscles. After the FDG PET/CT findings,
the CECT scan of the chest, abdomen, and pelvis was reviewed again, but no contrast-enhanced
lesions were seen in the localizations corresponding to the hypermetabolic muscle
lesions ([Fig. 2]).
Fig. 1 Increased fluorodeoxyglucose (FDG) uptake in the recurrent right pleural tumor (A, maximum intensity projection [MIP] images; B, axial fused positron emission tomography/computed tomography [PET/CT] images, yellow arrows), and two metastatic hypermetabolic small foci in the left pleura (B, axial fused PET/CT images, blue arrows). Multiple FDG avid foci of variable sizes in different skeletal muscle groups, including
left medial pterygoid muscle, paraspinal muscles, bilateral gluteal muscles, right
biceps brachii muscle, and extensively in the muscle groups of both lower extremities
(A, MIP images; B, axial fused PET/CT images, white arrows).
Fig. 2 Fluorodeoxyglucose (FDG) avid metastatic lesions are clearly seen in the left and
right paraspinal muscles (A, fused positron emission tomography/computed tomography [PET/CT] images, white arrows) and left gluteus medius muscle (A, fused PET/CT image, green arrow). No contrast-enhanced lesions are observed in the localizations corresponding to
the hypermetabolic muscle lesions and muscle density of the metastatic foci is similar
to normal muscles on contrast-enhanced computed tomography images, i.e., they are
isodense muscle metastases (B).
Biopsy from a relatively greater hypermetabolic muscle lesion located in the left
calf and histopathology confirmed metastatic epithelioid MPM. Histopathologic examination
demonstrated that invasion of the epithelioid neoplastic cells to the muscle tissue
was present. The neoplastic cells stained positively for CK 5/6, WT-1, CK7, and CK20.
Staining was negative for calretinin, thyroid transcription factor-1, carcinoembryonic
antigen, and CDX-2 in the immunohistochemical study ([Fig. 3]).
Fig. 3 Histopathology of a hypermetabolic lesion biopsied from the left calf confirmed metastatic
epithelioid malignant pleural mesothelioma (MPM). Invasion of the epithelioid neoplastic
cells to the muscle tissue (A, hematoxylin and eosin, ×100). Immunohistochemistry demonstrated positive staining
for CK 5/6 (B, ×200) and WT-1 (C, ×200).
In addition to local recurrence and contralateral pleural metastases, FDG PET/CT was
able to detect multiple muscle metastases, which were not observed on diagnostic CECT,
and revealed more extensive metastatic involvements of the skeletal muscles in the
presented case with MPM.
Discussion
MPM is a rare cancer with increasing incidence and poor prognosis.[9] Presentation with metastasis is rare and cases with distant metastases are diagnosed
more frequently during the clinical course of the disease.[10] Local metastatic spread is the major dissemination pattern. Distant dissemination
is uncommon. However, distant metastases from MPM are considered more common than
previously reported and can involve mostly the liver, spleen, lung, bone, adrenal,
kidney, thyroid, and peritoneum.[2]
[3] Metastatic involvement of the skeletal muscle is rare among distant organ metastases
in MPM. Not many but several MPM cases with distant muscle metastases have been reported
in the literature.[4]
[5]
[6]
[11]
[12]
[13]
[14]
[15]
[16]
[17] It was also noted that the most common histological type of tumor in those cases
was epithelioid MPM as observed in our patient.
FDG PET/CT imaging has been increasingly used for presurgical characterization and
staging at presentation, for evaluation of response to treatment, and restaging during
follow-up of patients with MPM.[6]
[7]
[8] Since FDG is a glucose analog, increased glucose use by malignant cells leads to
high FDG uptake. Functional PET data, that is, increased FDG uptakes in malignant
cells, along with anatomic CT data make FDG PET/CT a very useful and valuable imaging
modality in most of malignant diseases.
Multiple skeletal muscle metastases from MPM detected by FDG PET/CT was first reported
by Aukema et al.[12] FDG PET/CT was highlighted to be a superior and more effective imaging modality
than CT alone in the evaluation of distant metastatic disease of MPM.[2]
[3]
[6]
[12] In the presented case, in addition to local recurrence and contralateral pleural
metastases, PET/CT demonstrated extensive skeletal muscle metastases not suspected
before, but there were no morphologic abnormalities on diagnostic CT corresponding
to the hypermetabolic muscle lesions. As a result, FDG PET/CT provided more accurate
restaging of our case with MPM.
The presence of skeletal muscle metastases are usually a rare entity with most malignancies;
however, lung cancer has been reported as one of the most frequent causes of muscle
metastases.[18]
[19] Due to the increasing use of hybrid imaging using FDG PET with CT in recent times,
an increase in the frequency of detection of skeletal muscle metastases has been observed.[20] The exact underlying causes are not known yet, but there are some hypotheses as
to why metastatic involvement in muscles is so rare. Muscle motion and mechanical
tumor destruction, inhospitable muscle pH, and the ability of the muscle to remove
tumor-produced lactic acid that induces tumor neovascularization are considered to
act as defensive factors against the spread of the tumor.[21]
[22]
Conclusion
Rarely seen muscle metastasis in MPM may be missed on diagnostic CECT but FDG PET/CT
can detect unusual or unexpected distant metastases such as skeletal muscle metastases
and provides more accurate restaging of patients with MPM.
