Keywords
massive localized lymphedema - pseudosarcoma - soft tissue tumor - obesity - morphological
study - Introduction
Introduction
Massive localized lymphedema (MLL) is a rare benign soft tissue lesion that develops
in morbidly obese patients. This pseudotumor lesion is caused by obstruction of lymphatic
channels. MLL is sometimes called pseudosarcoma due to some macroscopic resemblance
to soft tissue sarcomas.[1]
[2]
MLL is characterized by slow growth, and more often affects females. Patients often
seek medical assistance during the late stages of the disease, when daily activity
is compromised. According to the literature data, the size of MLL may reach 62 cm
at the time of patient admission.[3]
Farshid and Weiss first described MLL as an enlarging lesion due to chronic lymph
obstruction;[4] hence, other terms were also proposed.[5] MLL is commonly localized on the inner surface of the thigh, followed by the anterior
abdominal wall.[6]
[7]
[8]
Morbid obesity and metabolic syndrome result in the obstruction of the lymphatic vessels,
ischemia, and proliferation of connective tissue. Posttraumatic damage to the lymphatic
vessels can also contribute to the development of lymphedema.[9]
MLL has its own clinical, radiological, and histopathological characteristics ensuring
the diagnosis of the obstruction of lymphatic vessels. The aim of our report is to
present the case of anterior abdominal wall MLL and discuss its clinical signs and
potential diagnostic methods, including morphological ones that can be considered
while treating this group of patients. It is the first time when electron-microscopic
(EM) study of biopsy specimens revealed the presence of interstitial Cajal-like cells
(ICLC) in MLL.
Case
A 50-year-old female was admitted to the Department of Plastic Surgery and Herniology
of our institution in February 2019 with a mass on the anterior abdominal wall extending
to the knees. The patient was morbidly obese with body mass index (BMI) of 62.5 kg/m2 at the age of 47 years. In 2016 after a stroke, she lost 44 kg of body mass. She
started to notice a mass in her hypogastric area in the form of an “apron” that had
flesh color and moderate density. This mass gradually started to grow, the density
became more pronounced, the skin surface was granular, the color became pink, and
then cyanotic. Skin started to itch and trophic changes with ulcerations and small
hemorrhages appeared ([Fig. 1]). The patient had difficulty walking and problems with sleep. Computed tomography
(CT) revealed a mass of the anterior abdominal wall in the hypogastric area, 27.5 cm × 31.4 cm × 33.1 cm
in size with well-defined borders ([Fig. 2]). Dilated, tortuous venous collaterals were visualized in the mass (–9.2 HU). The
skin was of uniform density and was thickened evenly. The subcutaneous adipose tissue
had a typical cellular structure due to longitudinal and radial fibrous cords. The
density of adipose tissue in the cells increased toward the skin (11 HU). There were
no other changes in the skin and subcutaneous tissue. All these features were suggestive
for benign changes, the absence of sarcoma so recommended surgical intervention followed
by complex pathological examination.
Fig. 1 Preoperative view of the patient with a massive local lymphedema of the anterior
abdominal wall. (A) Semilateral view. A patient is standing. (B) Lateral view. A patient is supine.
Fig. 2 CT-scan of the anterior abdominal wall MLL.
The patient underwent the anterior abdominal wall MLL resection ([Fig. 3]). The abnormal tissue was separated from aponeurosis and was removed. There was
bleeding from vessels, which were later ligated. The removed mass was 50 cm × 60 cm
in the size. The weight of the mass was 22.16 kg.
Fig. 3 Intraoperative photos. (A) Surgical access to the excised MLL. (B) View of the sutured abdominal wall after the excision of MLL. (C) Excised specimen.
On the cut sections, the dermis was 5 cm in depth with a whitish interlayer. Subcutaneous
tissue was edematous with few scattered blood vessels and fibrous whitish interlayer.
The transparent fluid was visible on the edges of the cut section ([Fig. 4A]). Histological examination revealed a morphological picture of MLL ([Fig. 4B–E]). The epidermis was with hyperkeratosis, dermis was fibrosis, dilated lymphatic
vessels, and infiltrated with reactive proliferative fibroblasts in the ulceration
zone. The subcutaneous tissue was composed of mature adipose tissue with marked diffuse
swelling and the presence of wide septa and multiple capillaries with perivascular
lymphoplasmacytic infiltration. There were no atypical adipocytes.
Fig. 4 Morphological view of the MLL. (A) Macropreparation (50 × 60 × 20 cm)—view of the cut section: the dermis is sharply thickened, there are marked fibrous
septa in the subcutaneous tissue. (B) Microscopical study (hematoxylin and eosin, ×50 magnification). Epidermis with hyperkeratosis.
Dermal fibrosis and hyalinosis, multiple, slightly enlarged lymphatic vessels. (C) Immunohistochemical (IHC) staining with Podoplanin (D2-40, ×50 magnification). Positive
reaction in lymphatic vessels. (D) Microscopical study (hematoxylin & eosin, ×100 magnification). Dilated lymphatic
vessels with perivascular lymphoplasmacytic infiltration in the fibrous thickened
dermis. (E) Microscopical study (hematoxylin & eosin, ×50 magnification).Subcutaneous tissue
consists of mature adipocytes with prominent edema, presence of fibrous septa, lymphoplasmacytic
infiltrate, reactive proliferation of capillaries. (F) Transmission electron microscope picture (scale bar: 2 μm) of the dermal blood vessel
segment surrounded by interstitial Cajal-like cells (ICLCs) projections. A telepode—a
triangle, a podomere—an arrow, a podom—a circle, endothelial cell—END, smooth muscle
cell—SMC. (G) Transmission electron microscopy (scale bar: 2 μm) of the ICLC in the dermal segment.
Long thin telepodes—a triangle; a podom—a circle. (H) Transmission electron microscope picture (scale bar: 1 μm) of the dermal lymphatic
vessel segment with detachment of vacuolated endothelial cells—(END) and increased
subendothelial space (the white arrow); smooth muscle cell—SMC.
An EM examination of the obtained tissue sample was performed ([Fig. 4F–H]). A specimen of 1 mm3 in size was cut, fixed in 2.5% glutaraldehyde and 1% osmium oxide (VIII). Then, the
specimen was dehydrated using increasing concentrations of alcohol (50, 70, 96, and
100%) and impregnated with a mixture of propylene oxide and araldite resin. After
impregnation, the specimen was transferred to capsules and filled with araldite resin,
and then placed in a thermostat at a temperature of 60°C for 2 days. The images of
light-optical examination were analyzed and recorded (section thickness of 1.0–1.5 µm,
stained with toluidine blue), including the area targeting for ultratomy. The ultrathin
sections of 100 to 120 nm in thickness were cut using an LKB ultramicrotome (Sweden).
Sections were stained with uranyl acetate and lead citrate and viewed under a JEM
100-CX electron microscope (JEOL, Japan) in the transmission mode at an accelerating
voltage of 80 kV.
ICLCs—telocytes were found in the dermis and subcutaneous tissue. These cells have
not been previously described in MLL. Multiple projections of ICLCs interacted with
smooth muscle cells (SMCs) of blood vessels ([Fig. 4F]). ICLCs had characteristic ultrastructural features: several prolongations—telopodes,
thin segments—podomers, and dilated segments—podoms ([Fig. 4G]). There were single ICLCs around lymphatic vessels with pronounced destructive changes,
but more often ICLCs were completely absent. Ultrastructural changes in ICLCs are
associated with the dysfunction of these cells. The ultrastructural analysis of the
walls of the lymphatic vessels showed the impairment of myendothelial and myo-myocytic
contacts, as well as collagenization of the vascular walls, detachment of endothelium
with fragmentation, enlargement of the subendothelial space, destruction of endothelial,
and SMC organelles ([Fig. 4H]).
There were no complications after surgery. The in-hospital length of stay was 10 days.
Upon follow-up in the 1styear, the patient did not have any complaints. No relapses were observed ([Fig. 5]). The quality of life significantly improved. BMI was 36.7 kg/m2.
Fig. 5 The view of the patient 1 year after the excision of MLL. (A) Anterior view. (B) Lateral view.
Discussion
The first cases of MLL as a distinct disease were described by Farshid and Weiss in
1998 after the investigation of tissue samples from 14 patients with morbid obesity.
Based on clinico-morphological similarities with diffuse lymphedema, the authors called
this process a MLL.[4]
Kohli et al described three similar clinical cases in 2013 and gave them a new name
- «Obesity-Associated Abdominal Elephantiasis»[5].
There are no statistically proven data about the prevalence of this pathology. The
main information is presented in the form of clinical cases.[6]
[7] Kurt et al reported a case series of MLL in 2016. In total, 54 cases of MLL were
found in 46 patients undergoing treatment in the years 2002 to 2015.[8]
The thigh is the most common location. Other sites were also described, including
the abdominal wall, pelvic area, vulva, penis, popliteal fossa, and an upper extremity.[6]
[7]
[8]
The main risk factors are morbid obesity and metabolic syndrome.[8] An increased amount of adipose tissue leads to an obstruction of lymphatic vessels
of the skin and subcutaneous tissue with the development of lymphedema, ischemia,
and increased deposition of connective tissue. Less common causes are trauma and surgical
intervention with damage to lymphatic vessels. Hypothyroidism also was reported as
a risk factor.[9]
The life quality of patients with MLL is significantly decreased due to immobility,
social isolation, difficulties with finding the appropriate size of clothes, and personal
hygiene. Successful rehabilitation may be performed after the surgical treatment.
However, the surgical method of the treatment can be complicated by difficulties in
identifying the margins of the pathological tissue, increased bleeding, and lymphorrhea.[10]
It is important to note that MLL is a clinical diagnosis. A preoperative biopsy is
not required and is rarely informative.[11] It requires multislice spiral computed tomography or magnetic resonance imaging
to exclude soft tissue sarcoma.[12]
[13] In the reported case, a CT study was also done to exclude the diagnosis of the anterior
abdominal wall hernia and malignant mass.
Shon et al consider lymphedema as a significant risk factor for the development of
angiosarcoma.[14] In total, 65 cases of MLL were described by 2015, and 9 (10.3%) of them progressed
to angiosarcoma.[15] According to Best and coauthors, MLL is a benign tumor, the excision of which is
desirable because it can progress to angiosarcoma in 13%.[16] Other authors also noted the malignization of MLL.[11]
[14] The mortality rate from MLL is 9% that justifies oncological alertness while diagnosing
MLL.[13]
[14]
[17]
Early diagnosis of MLL in obese patients remains challenging. In our case, the lymphedema
was only visualized after the decreased subcutaneous adipose tissue despite lymphatic
obstruction began to progress earlier. The lack of data for previous trauma, surgery,
and the presence of hypothyroidism confirm morbid obesity as the leading cause for
developing MLL in our patient. We excluded the likelihood of a malign process based
on the specific changes in the skin and subcutaneous adipose tissue according to CT
scans. The histological report has a significant role in the diagnosis of MLL. The
determining point is a histological confirmation which together with above-mentioned
findings gives the final diagnosis of MLL.
The etiology and pathogenesis of MLL is unclear but might be multifactorial. It might
be assumed that the destruction of ICLCs, first identified by electron microscopy,
decrease in their number or complete absence, and dysfunction of intercellular contacts
are factors that can influence the initiation and the development of MLL and promote
lymphatic stasis via decreasing the tone of lymphatic vessels. ICLCs are involved
in cell-to-cell communication. They form a complex three-dimensional extracellular
network via homocellular and/or heterocellular contacts with endothelial cells, SMCs,
and activated immunocytes. ICLCs coordinate long-distance intercellular connectivity.[18]
[19] Some authors consider ICLCs and SMCs interactions as one of the mechanisms that
explain the peristaltic contraction of lymphatic vessels.[20] Most likely, it is a complex signaling pathway that explains the role of the three-dimensional
extracellular network in the regulation of contractile activity of lymphatic vessels.
Decreased telocyte numbers might be an important etiopathogenic factor in the development
of MLL.
Thus, we may conclude that MLL is a complication of obesity that significantly reduces
the quality of life and requires surgical treatment according to the literature analysis
and our experience. It has its own clinical and instrumental features that allow diagnosing
this rare disease.
