Archives of Medicine and Health Sciences

CASE REPORT
Year
: 2022  |  Volume : 10  |  Issue : 1  |  Page : 81--83

Giant sacral xanthoma in familial hypercholesterolemia


Abha Singh, Neha Aggarwal, Sunayana Misra 
 Department of Pathology, ABVIMS and Dr RML Hospital, New Delhi, India

Correspondence Address:
Dr. Sunayana Misra
Department of Pathology, ABVIMS and Dr RML Hospital, Room - 323, OPD Block, 3rd Floor, New Delhi - 110 001
India

Abstract

A 28-year-old male patient presented with multiple large, superficial, nodular masses in his elbows, buttocks, knees, Achilles tendons, feet, shoulders, and hands along with small xanthomatous lesions on the face, inner epicanthal region; largest mass being in the sacral region measuring 15 cm × 12 cm × 8 cm. The patient also presented with an elevated level of low-density lipoprotein cholesterol and was diagnosed with familial hypercholesterolemia (FH) presenting with multiple xanthomas. Local surgical excision was performed to remove the massive xanthoma from the sacrum, histopathology of which showed sheets of foamy lipid-laden histiocytes dissecting through the dermis and subcutaneous fat. The presence of long standing and/or multiple xanthomas often indicates severe and long-term FH. A thorough systemic workup is needed for such patients, especially to rule out cardiovascular complications so that lipid-lowering agents and dietary modifications can be initiated early on. We present the case of a young male patient with FH presenting with multiple large tuberous xanthomas all over the body.



How to cite this article:
Singh A, Aggarwal N, Misra S. Giant sacral xanthoma in familial hypercholesterolemia.Arch Med Health Sci 2022;10:81-83


How to cite this URL:
Singh A, Aggarwal N, Misra S. Giant sacral xanthoma in familial hypercholesterolemia. Arch Med Health Sci [serial online] 2022 [cited 2022 Aug 19 ];10:81-83
Available from: https://www.amhsjournal.org/text.asp?2022/10/1/81/347956


Full Text

 Introduction



Xanthomas are skin lesions caused by the accumulation of fat in macrophages within the skin. The clinical picture can vary from dermal macules or papules to subcutaneous plaques and nodules. Although they may appear nodular and tumorous, they are formed by aggregates of lipid-laden macrophages in the connective tissue of skin, tendons, and subcutaneous tissues. Xanthomas comprise important clinical manifestations of lipid metabolism disorders being commonly encountered in patients with familial hypercholesterolemia (FH).[1]

Xanthomas may be divided into several categories: Tendinous xanthoma, xanthoma tuberosum, eruptive xanthoma, xanthoma planum, and palmar xanthoma, of which tendinous xanthomas are most common. FH is an inherited disorder featuring elevated plasma levels of low-density lipoprotein cholesterol (LDLC), total cholesterol (TC), atherogenesis, and multiple xanthomas. Two clinical variants of FH exist, homozygous (HoFH) and heterozygous (HeFH). Clinical manifestations associated with xanthomas depend on the duration and severity of hyperlipoproteinemia; therefore, the presence of multiple xanthomas often indicates severe and long-term FH and is usually observed in patients with HoFH.[1],[2] We report the case of a 28-year-old male patient with FH, who presented with multiple large tuberous and tendinous xanthomas within various dermal tissues.

 Case Report



A 28-year-old male patient presented to surgery clinic with multiple yellowish, elevated masses over the dorsum of elbows, knees, buttocks, and hands [Figure 1]. The size of the masses varied from 1 cm (over elbows) to 15 cm (over the sacral region). The lesions were originally asymptomatic; appeared few years back and progressively increased in size. At present, the patient had symptoms of discomfort in buttocks. His plasma TC and LDLC levels were 441 g/dl (reference value, 130–230 g/dl) and 375 mg/dl (reference value 50–150 mg/dl). Magnetic resonance imaging revealed a subcutaneous mass in the sacrum which was iso-intense to muscle and showed hyperintense foci on fat-suppressed sequences [Figure 2]. His father had a history of coronary heart disease (CHD) and was treated with percutaneous coronary intervention 2 years ago but expired soon after. His paternal uncle had similar symptoms; underwent coronary artery bypass grafting 1 year back and is presently stable. Mother and other siblings are asymptomatic. The patient was diagnosed with FH with xanthomatosis. Due to the symptomatic nature of the sacral lesion, it was excised and sent for histopathology [Figure 2].{Figure 1}{Figure 2}

Microscopic examination revealed sheets of foamy histiocytes, giant cells, and cholesterol clefts dissecting through the dermis and subcutaneous fat [Figure 3]. These findings confirmed the diagnosis of xanthoma. Treatment with Rosuvastatin and Ezetimibe started at diagnosis was continued postoperatively, dose of rosuvastatin was adjusted to 20 mg/day. The patient has been advised to take note of any chest tightness and other symptoms of CHD as well as undergo cardiac examination 6-monthly.{Figure 3}

 Discussion



Xanthomas refer to lesions on the skin associated with raised levels of LDL. They can be single or multiple varying in size from 0.5 to 10 cm. The presence of multiple xanthomas from an early age point toward FH. HeFH accounts for majority of FH cases, with an approximate incidence of 1 per 500 individuals; whereas HoFH is considerably rare, with an incidence of 1 per 1,000,000 individuals. FH is inherited in an autosomal dominant manner. HeFH becomes symptomatic in the 3rd to 6th decades and responds well to treatment. The presence of multiple xanthomas, enlarged achilles tendons, atherosclerosis, corneal arcus, blood LDLC of >13 mmol/l (>600 mg/dl), TC levels >14.95 mmol/l (>1200 mg/dl), and disease onset in early childhood points toward HoFH.[2]

In FH, markedly elevated LDLC levels are secondary to LDL receptor defects resulting in lipid leakage from the vasculature into surrounding tissues and uptake by tissue macrophages.[3] Previous studies suggested that mechanical predisposes these sites to the development of xanthomas due to increased capillary permeability and LDLC accumulation.[4] Ultrasonography is a simple, widely available and economical modality used for the identification of xanthomatosis; however, magnetic resonance imaging is the best available noninvasive ancillary investigation for the diagnosis [Figure 2]. Histopathology is the gold standard for confirmation of diagnosis.

Close differentials of xanthoma include benign fibro-histiocytic tumor, Langerhans cell histiocytosis (LCH), xanthoma disseminatum (micronodular form of juvenile xanthogranuloma), and generalized eruptive histiocytoma. LCH manifests histologically as numerous histiocytic cells with an abundant pale cytoplasm and eccentric, indented, coffee bean nuclei, but few clear cells and no touton giant cells. Eruptive histiocytoma shows abundance of xanthomized perivascular histiocytes and the presence of lipid deposits. Xanthoma disseminatum is usually solitary and seen in children.

Several cases of giant xanthomas have been reported but most of them described are at very young age.[5],[6] All of them were associated with HoFH. Majority cases have reported the presence of multiple xanthomas at friction prone areas such as buttocks, elbows, and knees. To the best of our knowledge, largest xanthoma described in the literature is 20 cm, while in our case, the sacral xanthoma was as large as 15 cm[4] [Table 1].{Table 1}

Our case elevated TC and LDLC levels with a history of similar complaints in father as well as paternal uncle suggesting a high likelihood of HeFH.[5] Secondary hypercholesterolemia, due to hypothyroidism, diabetes, renal or hepatic disease were excluded since random blood sugar, kidney function tests, and liver function tests were within the normal limits. The patient was advised close follow-up in view of high LDL and levels and multiple xanthomas.

Dyslipidemias are categorized from type I to type V based on the genetic defect, varied clinical presentation, and variable lipid profiles. While type I is characterized by a defect in LPL gene with increased chylomicron and triglycerides levels while type V has unknown cause with additional raised VLDL and cholesterol levels. FH is most commonly associated with patients of Type II dyslipidemia (both homo- and heterozygous states) with a genetic defect in LDL receptor. Type III is associated with defect in Apo E gene causing increase in triglycerides as well as intermediate-density lipoprotein cholesterol level while Type IV has unknown genetic etiology with increased VLDL levels.[10]

 Conclusion



In patients of FH, the presence of xanthomas increases the risk of cardiovascular disease by three fold. If left untreated, it may rapidly lead to atherosclerotic changes causing aortic stenosis and coronary artery disease.[8],[11] Early diagnosis of FH and prompt initiation of diet and lipid-lowering therapy are important to prevent future risk of cardiovascular disease. Genetic testing may provide a definitive diagnosis, but if unavailable, markedly elevated LDLC levels together with cutaneous or tendon xanthomas, or untreated elevated LDLC levels are consistent with heterozygous FH.

Purpose of this case report is to highlight the importance of clinico-pathologic correlation supporting the clinical diagnosis of FH.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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