3. Discussion
Parathyroid lipoadenomas are rare and are incidentally detected during
thyroid cancer surgery in this case. In this paper, 40 literatures with
”parathyroid lipoademona” as search term on PubMed[1,2,4,5, 7-42] and 65 cases of parathyroid
lipoadenoma (including this case) were counted. After excluding 18 cases
with missing clinical data, 47 cases had complete clinical data,
including 30 females and 17 males, with a female-to-male ratio of about
1.8:1, that is, parathyroid lipoadenoma accounted for a higher
proportion in females than in males. In addition, it has been reported
in the literature that parathyroid lipoadenoma may account for a higher
proportion in males than parathyroid adenoma [1].
The age of onset of parathyroid lipoadenomas varies from 24 to 88 years,
mostly located in the neck, but up to 15% of parathyroid lipoadenomas
are ectopic or located in the mediastinum, much higher than common
parathyroid adenomas[2].
In 1958, Ober and Kaiser[3] first described
parathyroid lipoadenoma in a middle-aged man with a gradually enlarging
neck mass that was painless and without manifestations of
hyperparathyroidism.A large lipoma was found under the sternum on neck
exploration.Because the tumor was nonfunctional, they named it
”parathyroid hamartoma”.The concept of ”parathyroid lipoadenoma” was
first introduced in 1962 by Abul Haj [4] et
al.Parathyroid lipoadenoma is a rare type of parathyroid adenoma with an
incidence of 0.5% to 1.6% of primary hyperparathyroidism and contains
fat, principal cells, and eosinophils, of which fat content is
> 50%, unlike adenomas with fatty infiltration, and the
fat component is an integral part of parathyroid
lipoadenoma[5].In 2022, the World Health
Organization defined parathyroid lipoadenoma as ”a tumor with
simultaneous increases in parathyroid parenchyma and adipose tissue, and
more than 50% of the glandular volume consists of adipose
tissue”[6].In the currently reported cases of
parathyroid lipoadenoma, the origin of the adipose tissue component is
unknown, and most of them are small brown lesions with the largest
reported weight of 480 g.Some researchers have speculated that the
factors of increased fat composition may be the same as those of
increased parathyroid chief cells [7,8].It has
been suggested that fat may be present in adenomas by high BMI, and some
speculations suggest that some adipogenic factors may be produced by
adenoma epithelial or stromal cells, which in turn stimulate adipocyte
proliferation[9].Christofer Juhlin proposed that
parathyroid lipoadenomas may be associated with
hypertension[5].
Parathyroid lipoadenomas can be classified as functional and
non-functional, with approximately 64 percent of previously reported
cases symptomatic, 28 percent asymptomatic, and 7 percent
suspicious[10,11], and four parathyroid
lipoadenomas found on autopsy for which function is uncertain. Among
them, the clinical features, laboratory tests and parathyroid adenomas
of functional parathyroid lipoadenomas are similar, that is, patients
show recurrent urinary stones and hip or shoulder fractures, but the
increase in parathyroid hormone and blood calcium may not be as obvious
as parathyroid adenoma, and a very small number of patients have
asymptomatic hypercalcemia.
The difficulty of parathyroid lipoadenoma is mainly diagnosed by
preoperative imaging localization.29 of 64 patients (45%) had lesions
localized using imaging studies.Ultrasonography was performed in 24
cases, and lesions or suspected lesions were found in 14 (58%) of
them.Computed tomography(CT) was reported in 12 cases, of which 9 (75%)
detected or suspected lesions.Technicium-99m sestamibi scintigraphy was
reported in 15 cases, of which 8 (53%) reported detection or suspicion
of lesions.In one of them, an X-ray was performed and the tumor was
found to be located in the mediastinal cavity.Positron emission
tomography (PET) scans were used in 6 cases, of which 3 (50%) were
reported as lesions.Because of the high adipose tissue content, lipomas
tend not to be detected by preoperative imaging techniques.On
ultrasound, typical parathyroid adenomas are homogeneous hypoechoic
lesions, however, fat-rich variants of parathyroid adenomas sometimes
present as hyperechoic lesions [9], resulting in
reduced accuracy, and ultrasound examination of this patient showed no
parathyroid lesions; they can be localized as lipomatous masses on CT,
and Johnson et al[12] reported cases in which CT
scans of parathyroid lipoadenomas had CT values of − 60 to − 90 HU,
consistent with lipoma density, proposing the possibility of parathyroid
lipoadenomas on such CT scans in similar cases of non-local primary
HPT.However, CT may also be confused with lipomas, lymph nodes, or other
fat-rich lesions; the accuracy of dual-phase Sestamibi scanning of the
parathyroid depends on the proportion of parathyroid chief cells, which
are more than 50% fat in parathyroid lipoadenomas and have less
principal cell content than normal parathyroid tissue, resulting in
reduced accuracy of Sestamibi scanning; however, there are cases[13] indicating the usefulness of using 99Tcm-MIBI
imaging in localizing the diagnosis, reoperation, and persistent
hyperparathyroidism, and they propose speculation that the lesion may be
shown based on the space-occupying appearance, or that the target may
have a low signal ratio to the background.Cases showed a good
target-background signal ratio in Tc-99m sestamibi imaging, which may be
due to the relatively large size of the lesion, as well as the fact that
the main part of the lesion consists of parathyroid chief cells; the
sensitivity of syngeneic SPECT for parathyroid lipoadenoma was
significantly reduced [12].However, Sabri et
al.[1]concluded that although SPECT is not as
effective as parathyroid adenoma in the diagnosis of parathyroid
lipoadenoma, it may be superior to ultrasound.Cholinergic PET-CT imaging
is superior to ultrasound and CT in the localization of parathyroid
adenoma, but there is no relevant report for parathyroid lipoadenoma.
Primary hyperparathyroidism is most commonly caused by solitary
parathyroid adenomas, accounting for more than 80 – 85%; less
commonly, parathyroid hyperplasia, parathyroid carcinoma, and multiple
parathyroid adenomas[2]. Parathyroid lipoadenoma
is a very rare cause of primary hyperparathyroidism with an incidence of
0.5% to 1.6% of primary hyperparathyroidism. In parathyroid
lipoadenomas, the sensitivity of imaging is significantly reduced by low
parathyroid cell concentration and excessive fat content. Abundant
adipocytes in parathyroid tissue can be found in the following
conditions: normal tissue, lipohyperplasia, lipoadenoma, and cancer
infiltrating the surrounding adipose tissue. It is difficult to
differentiate these diagnoses by intraoperative rapid frozen section.
Therefore, definitive diagnosis of parathyroid lipoadenoma should
include pathologic diagnosis of parathyroid hyperplasia within adipose
tissue, as well as a significant decrease in hormone following
intraoperative removal of the parathyroid gland. Increases in
parathyroid gland weight (> 40-60 mg) may also represent
parathyroid lipoadenomas in appropriate morphologic and clinical
settings [6]. Parathyroid lipoadenomas should be
considered when no lesions are reported on ultrasound but clearly
identified by CT or SPECT. Parathyroid carcinoma infiltrating in adipose
tissue may be misdiagnosed as parathyroid lipoadenoma, so careful
pathological examination is still required for differential diagnosis.