Introduction
Leiomyosarcoma is a soft-tissue neoplasm of smooth muscle origin. Primarily, it occurs
in the myometrium, retroperitoneum, or dermis of the extremities; primary leiomyosarcoma
of the adrenal gland is very rare. Till date, only 30 patients have been reported.
Here, we report another case of primary adrenal leiomyosarcoma and review of the clinical
and pathological characteristics.
Case Report
A 60-year-old female presented with a 2 years’ history of left abdominal pain radiating
to the back. There were no constitutional symptoms, as well as recent weight loss.
There was no history of hypertension, diabetes, and tuberculosis, and her HIV antibody
was negative. Physical examination showed mild abdominal discomfort on palpation.
Computed tomography was performed, which revealed a well-circumscribed heterogeneous
mass measuring 7.6 cm × 7.7 cm × 6.8 cm located in the left suprarenal area, abutting
distal pancreas, and kidney [Figure 1]. Neither venous thrombosis nor metastatic lesions were noted. Twenty-four hours
urine collections for cortisol and catecholamines were normal, as were serum aldosterone
and adrenocorticotrophic hormone levels.
Figure 1: Preoperative and postoperative images of left adrenelectomy
Question 1
What are the most common causes of such a presentation?
Answer
-
Benign adrenocortical adenoma
-
Adrenocortical carcinoma
-
Pheochromocytoma/paraganglioma.
Other rare causes are neuroblastoma and nonprimary adrenal masses such as adrenal
metastases, sarcomas, lymphomas, myelolipomas, and ganglioneuromas.
Based on the clinical diagnosis of nonfunctional adrenal tumor, a left adrenalectomy
with splenectomy and distal pancreatectomy was performed.
Pathological examination: Gross pathological examination showed an encapsulated solid
mass measuring roundish 9 cm × 8 cm × 7 cm. The tumor tightly abutted the stretched
identifiable adrenal gland and part of the pancreas. There were areas of hemorrhage.
The microscopic examination revealed a spindle cell neoplasm. There was necrosis with
a mitotic rate of 5–6/10 HPF. There was a lesion abutting adjacent pancreas. Margins
were free.
Morphologically adrenal gland with tumor surface interface [Figure 2a], low power spindle fascicle with pleomorphic cell [Figure 2b], On immunohistochemical studies, the tumor cells stained positive for smooth muscle
actin (SMA) [Figure 2c], desmin [Figure 2d], h-Caldesmon [Figure 2e] and CD34, and negative for CD117, S100, and DOG 1. The proliferation rate of ki67
was high (40%) [Figure 2f]. Based on the histopathological and immunohistochemical findings, the diagnosis
of an adrenal leiomyosarcoma was made.
Figure 2: (a-f) Adrenal gland with tumor interface, low power spindle fascicle with
pleomorphic cell, smooth muscle actin, Desmin, h-Caldesmin, and Ki 67, respectively
Question 2
What are the differential diagnosis of Primary Leiomyosarcoma of adrenal gland (PLAG)
-
Reroperitoneal or metastatic leiomyosarcoma
-
Primary rhabdomyosarcoma
-
Undifferentiated pleomorphc sarcoma.
The postoperative period was uneventful; the patient was planned for adjuvant chemotherapy
with ifosfamide with Adriamycin regimen.
Question 3
How common is leiomyosarcoma of the adrenal gland?
PLAG is extremely rare and was first described by Choi and Liu in 1981.[1] Till date, only 30 cases of PLAG have been reported [Table 1].
Table 1
Summary of previously reported cases of primary adrenal leiomyosarcoma
|
References
|
Age
|
Treatment
|
Follow up/months
|
Pathological feature
|
|
Bil – Bilateral; ND – Not determined; IVC – Inferior vena cava; AO – Adjacent organ;
Adx – Adrenalectomy; Nx – Nephrectomy; RT – Radiation therapy; CT – Chemotherapy;
RFA-Radiofrequency ablation; S – Smooth muscle actin; NSE – Neuron-specific enolase;
D – Desmin; V – Vimentin; P – Pleomorhic; A – Actin
|
|
Choi and Liu[1]
|
50
|
Adx.+ Partial Nx
|
12 (alive without R/M)
|
N+D
|
|
Lack et al.
[2]
|
49
|
Adx.+ Partial Nx+RT+CT
|
9 (alive)
|
V+A+S
|
|
Zetler et al.
[3]
|
30
|
Adx
|
20
|
S
|
|
Boman et al.
[4]
|
40
|
ND
|
ND
|
S
|
|
Etten et al.[5]
|
73
|
Exploratory laparotomy
|
3 weeks (dead)
|
S
|
|
Matsui et al.[6]
|
61
|
Adrx+Nx+Thrombectomy
|
1 (dead metastasis)
|
S
|
|
Lujan and Hoang[7]
|
63
|
CT+Adx+Nx+hepatic lobectomy+cholecystectomy
|
Dead shortly after sx
|
|
|
Thamboo et al.[8]
|
68
|
Adx+Nx +
|
12
|
S+V+A+D
|
|
Linos et al.[9]
|
14
|
B/l Adx
|
ND
|
S+V+A+H
|
|
Kato et al.[10]
|
59
|
Adrx+Nx+Thrombectomy
|
6
|
P+S+V+D
|
|
Wong et al.[11]
|
57
|
Adrx+Nx+Thrombectomy
|
6
|
N+D
|
|
Candanedo-González et al.
[11]
|
59
|
Adx+CT+RT
|
36
|
P+V+A+D
|
|
Lee et al.[13]
|
49
|
Adx
|
10
|
D
|
|
Mohanty et al.[14]
|
47
|
Adx+Nx+RT
|
47
|
P+V+A+D
|
|
Wang et al.[15]
|
64
|
Adx+thrombectomy
|
10
|
S+D
|
|
Gotto et al.[16]
|
73
|
Adx+Nx
|
10
|
S+N
|
|
Mencoboni et al.[17]
|
75
|
Adx
|
12
|
S+A+D
|
|
Van Larhoven et al.[18]
|
73
|
RT
|
10
|
S+A+V
|
|
Hamada et al.[19]
|
62
|
Bil Adx+CT+RFA+RT
|
16
|
S+M+A
|
|
Karaosmanoglu and Gee[20]
|
68
|
CT
|
3
|
A+V+D+K
|
|
Shao et al.[21]
|
66
|
Adx
|
18
|
S+D
|
|
Kanthan et al.
[11]
|
28
|
Adx+Nx+partial diaphragmatic
|
ND
|
P+S+V
|
|
Desmukh et al.[23]
|
60
|
Adx
|
ND
|
S+V+D
|
|
Gulpinar et al.[24]
|
48
|
Adx
|
8
|
S+V
|
|
Oztmk[25]
|
70
|
Adx+cavatomy+CT
|
6
|
S+D
|
|
Lee et al.[26]
|
28
|
Adx
|
18
|
S+D
|
|
Bhalla et al.[27]
|
45
|
CT
|
9
|
S+D
|
|
Wei et al.[28]
|
27
|
Adx
|
29
|
S+V+A+D
|
Discussion
Almost all clinically reported cases to date are elderly patients with large tumors.
It is believed to originate from the smooth muscle wall of the central adrenal vein
and its branches. Most patients present with abdominal or flank pain and some also
present with lower limb edema and spider angioma when the tumor invades to the inferior
vena cava. Incidence of Leiomyosarcoma of adrenal gland is similar in male and female.
There is equal probability of either right or left adrenal gland origin. Most of the
reported cases are of conventional type and only five cases are of pleomorphic variety.
It is interesting to note that four of the patients were immunodeficient due to HIV
or Epstein–Barr virus infection. It seems that primary adrenal leiomyosarcoma (PAL)
is likely to occur in an immunosuppressive situation, but nothing certain is known
about the pathogenic involvement of these viruses.
As PLAGs do not produce any adrenal hormonal derangement and grow rapidly, there are
no applicable tumor markers or imaging characteristics available for making a preoperative
diagnosis, and all the cases were diagnosed after surgery or at necropsy. Encouragingly,
Goto et al. reported a case of neuron-specific enolase (NSE)-producing PAL. The level of serum
NSE was markedly high preoperatively and NSE protein was massively expressed in the
resected tumor. After the surgery, serum NSE levels became normal. It is suggested
that serum NSE levels could be a useful hallmark for the early detection for PAL.
However, Kato et al. found that immunostaining for NSE was negative in their case. Hence, we need further
research to seek a suitable tumor marker.
Histopathological and immunohistochemical evaluation is indispensable not only for
determining tumor type but also for differential diagnosis. Conventional leiomyosarcomas
show strong immunoreactivity for smooth muscle markers such as SMA and/or muscle-specific
actin in 90%–95% of cases and desmin in 70%–90% of cases. However, there is a marked
variability in the expression of these markers in pleomorphic leiomyosarcomas. Oda
et al. reported that 37.5% of the pleomorphic leiomyosarcomas of various sites are desmin
positive, 46.4% are muscle-specific actin positive, and 50% are SMA positive. Malignant
fibrous histiocytoma, malignant melanoma, malignant hemangioperistoma, angiosarcoma,
liposarcoma, carcinosarcoma, rhabdomyosarcoma, adrenal invasion by a retroperitoneal
leiomyosarcoma, and metastatic tumors should be considered in the differential diagnosis
of adrenal leiomyosarcomas.
Radical surgery is the mainstay of therapy, but the prognosis for PLAG patients is
not predictable. It is believed that in patients with invasive diseases that include
venous thrombosis, adjacent organ invasion, and distant metastases, the prognosis
is extremely poor. We found that in all these 28 cases, 12 patients who had no recurrence
or metastasis were almost without invasive diseases and none of them underwent any
adjuvant therapy such as chemotherapy or radiotherapy. Adjuvant therapy combined with
surgery is often used for PLAG patients with poor prognosis. In a systematic overview
study, Strander et al. showed that postoperative adjuvant radiation therapy was recommended for the treatment
of locally advanced malignancy in soft-tissue sarcomas. Radiation therapy and/or chemotherapy
may be helpful to shrink the tumor and destroy the remaining tumor cells.
Conclusion
Primary adrenal leiomyosarcoma is an extremely rare mesenchymal tumor. Early and complete
surgical resection is the mainstay management with PFS benefit of adjuvant chemotherapy
with ifosfamide and doxorubicin.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
In the form the patient(s) has/have given his/her/their consent for his/her/their
images and other clinical information to be reported in the journal. The patients
understand that their names and initials will not be published and due efforts will
be made to conceal their identity, but anonymity cannot be guaranteed.
