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Review paper

Rare skin tumours in organ transplant recipients

Beata Imko-Walczuk
1, 2
,
Joanna Renczyńska-Matysko
3
,
Damian Kadylak
1
,
Alicja Dębska-Ślizień
4

1.
Dermatology and STD Outpatient Clinic, Copernicus Medical Centre, Gdansk, Poland
2.
Department of Physiotherapy and Health Sciences, School of Management, Gdansk, Poland
3.
Department of Dermatology, Copernicus Medical Centre, Gdansk, Poland
4.
Department of Nephrology, Transplantology and Internal Diseases, Medical University of Gdansk, Gdansk, Poland
Adv Dermatol Allergol 2020; XXXVII (6): 862–870
Online publish date: 2021/01/06
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Introduction

Skin cancers, which originate in epidermis, such as squamous-cell carcinoma (SCC) and basal-cell carcinoma (BCC), have been thoroughly investigated. Their characteristic clinical symptoms, etiopathogenesis and risk factors have been a subject of many publications in medical journals [1, 2]. Conversely, there are very few reports on the subject of adnexal skin tumours.
A small incidence of the above-mentioned tumours in general population makes it difficult to assess their incidence in organ recipients. Even though a possibility of developing such tumours spontaneously cannot be entirely ruled out within this population, it seems that immunosuppressive therapy stimulates their growth as it occurs in case of non-melanoma skin tumours: SCC, BCC, lymphomas or Kaposi’s sarcoma.
There are few reports on the subject of adnexal tumours’ incidence in organ recipients. The majority of published studies include only incidental cases or are based on the research conducted on small groups of patients. Moreover, epidemiologic data regarding adnexal skin tumours in general population are also insufficient, which causes trouble in assessing the actual increase of the relative risk of these rare tumours in organ recipients.
The analysis of clinical features and pathology of tumours originating from skin appendages in organ transplant recipient (OTR) population seems to be of great importance as they may resemble other, more frequent tumours. It should be remembered that the course and the prognosis of adnexal tumours in OTRs on immunosuppression may be far worse than in the general population, including increased mortality.
There are various types of mesenchymal tumours that constitute a group of adnexal skin tumours, however this term is usually limited to describing tumours that originate or differentiate within the epithelium of these structures (eccrine, apocrine, sebaceous glands, hair follicle and matrix).
The World Health Organization (WHO) divides adnexal skin tumours into three groups, additionally distinguishing their malignancy: 1) of eccrine or apocrine origin; 2) originating from hair follicle; 3) originating from sebaceous glands [2, 3] (Table 1).

Epidemiology

Reliable data regarding the incidence of adnexal skin tumours in organ recipients are scarce as the studies usually include small groups of patients or solitary cases.
In 2003, Harwood et al. conducted the first large study that aimed to analyse the connection between organ transplantation and the occurrence of adnexal skin tumours. Additionally, it aimed to compare the incidence of adnexal skin tumours in patients on immunosuppressive treatment with their incidence in general population. There were 178 diagnoses of adnexal tumours in the population of 6000 immunocompetent patients (0.03%), compared to 21 cases of such tumours in the population of 650 organ transplant recipients (3%). The average period of time between the transplantation and the occurrence of the tumour was 9.8 years. The anatomical pattern was similar in both groups: most lesions developed in the head and neck area (67% in immunocompetent patients, 74% in OTRs).
In the above-mentioned study, malignant tumours accounted for 8.7% of all lesions. They were significantly more frequent in OTR population – 43%, compared to 4% in general population (p < 0.0001). Both groups differed from each other in terms of the degree of cellular atypia, inflammatory response and the presence of HPV within the lesions [4].
In 2007, the same authors presented results of a study conducted on a cohort of over 1000 OTRs. They described 23 malignant adnexal tumours in 21 OTRs. The following types of adnexal tumours were detected: 8 cases of sebaceous carcinoma, 5 foci of eccrine porocarcinoma, 4 cases of hidradenocarcinoma, 2 cases of microcystic adnexal carcinoma, 1 case of mucinous carcinoma, apocrine carcinoma and 2 cases of eccrine carcinoma originating from ductal hidradenoma in situ [2].
So far, 42 invasive foci of adnexal cancers have been described in medical journals, in which 17 were of apocrine or eccrine origin (40.48%), 22 featured sebaceous differentiation (52.38%) and 3 originated from hair follicle (7.14%). In our practice we detected sebaceous carcinoma in two OTRs (Table 1).

Pathogenesis

The aetiology of adnexal skin tumours in OTRs is unclear. It is believed that immunosuppressive drugs, ultraviolet radiation, genetic factors and HPV infection may constitute potential risk factors.
Immunosuppressive drugs may enhance carcinogenesis independently of their principal effect. Cyclosporine A may serve as a good example – it causes follicular matrix hyperplasia and dysplasia [5, 6]. Azathioprine combined with UVA radiation may specifically affect growth of tumours originating from sebaceous glands [7, 8]. Comparing the incidence of tumours in this group of patients with other groups of patients with immunosuppression (e.g. HIV-infected patients), it has been concluded that the major risk factor was the immunosuppressive effect of these drugs rather than their direct carcinogenic effect.
A tendency to develop adnexal skin tumours in sun-exposed areas and their frequent co-occurrence with tumours linked to UV exposure prove that UV radiation plays an important role in pathogenesis of tumours within this group [4]. The analysis of molecular disorders that are present in adnexal tumours further supports this hypothesis [9]. Malignant adnexal skin tumours occur more commonly in patients who underwent transplantation in older age and absorbed a higher cumulative dose of UV-radiation [10–13].
Genetic predisposition for developing adnexal skin tumours have been thoroughly studied in Muir-Torre and cylindromatosis syndromes. DNA repair gene mutations are an underlying cause of Muir-Torre syndrome (MTS), which is characterized by the presence of multiple sebaceous adenomas. Cylindromas and other adnexal tumours within the cylindromatosis syndrome are a consequence of hereditary loss of the CYLD1 tumour suppressor gene, whose locus is located on chromosome 16q [14–16]. The existence of multiple trichoepitheliomas is linked to chromosome 9q21 and some sporadic cases may involve a deletion within 9q23.3 chromosome, containing the PTCH gene. Tumours originating from the outer root sheath (trichilemmoma) contain PTEN gene mutations, which are connected with Cowden syndrome, SOLAMEN and Proteus syndrome [17–20].
Human papilloma virus (HPV) is considered to be a co-carcinogen for squamous-cell carcinoma in OTRs. A suggested influence of HPV on carcinogenesis of adnexal tumours is not sufficiently documented. In studies on animal models, the Mouse Papilloma Virus was detected in cases of spontaneous trichoepithelioma and sebaceous gland tumours in striped field mice from the European region [21]. In Japanese studies regarding cases of eyelid sebaceous carcinoma, in 13 out of 21 tumours, HPV-6, 11, 16, 18, 31, 33 DNA was found. The above-mentioned types of HPV were also isolated from healthy nuclei of sebaceous cells and epidermis surrounding the tumours [22]. HPV-20, 23 and HPV-DL332 were detected in solitary syringomas [23]. Data from studies regarding skin of palms of the hand suggest that HPV-63 virus occupies keratinocytes within the area of eccrine ducts or their surroundings. The microscopic examination shows the link between HPV in cases of papillary tubular adenoma and syringocystadenoma papilliferum, even though in identification studies limited to HPV types 2, 6/11, 16 and 18, no viral DNA was found [24, 25]. Studies on a connection between HPV and adnexal tumours are currently underway.

Clinical features of adnexal skin tumours

Both benign and malignant adnexal skin tumours are most commonly diagnosed during microscopic examination. Nodular lesions that later prove to be adnexal skin tumours have certain clinical features that facilitate the correct diagnosis. The usual location of the tumour is consistent with the presence of skin appendages. Apocrine tumours located in the armpits or anogenital area may serve as a good example.
Benign tumours are more frequently observed in young people. They are usually skin-coloured or red-brown papules or nodules with smooth surface. Malignant tumours, on the other hand, usually feature irregular, ulcerating lesions or nodules [3]. These tumours are often misdiagnosed as more common skin conditions like SCC, BCC or metastases from internal organ tumours. A diagnosis of a certain type of adnexal skin tumours may carry important implications for the patient’s health as some of these tumours form a part of paraneoplastic syndromes connected to cancer of internal organs. These relations are frequently observed in OTRs. Muir-Torre syndrome is a good example as it features both multiple sebaceous gland tumours and gastrointestinal tract tumours [26].
The majority of benign lesions are formed de novo, however, sometimes they can originate from sebaceous warts, epidermal, dermal and adnexal hamartomas. Also, malignant lesions mostly develop de novo and only sporadically as a transformation of previously benign tumour.
Metastases are seldom within this group, even in low-grade tumours. If present, they metastasise via the circulatory and lymphatic system. Eccrine cancer tends to form skin metastases [3].

Microscopic structure

Tumours originating from skin adnexa demonstrate follicular, glandular or ductal differentiation. Genesis of many of them remains unknown and the diagnosis is mainly based on their morphology. Microscopic diagnostics of adnexal tumours may cause problems even for experienced pathologists.
A full and appropriate assessment of tumours originating from hair follicle is the least problematic because of their tendency to create trochoidal ‘swirls’ and structures resembling the hair papilla.
Hallmarks that suggest sebaceous differentiation include foam cells with coarse granular cytoplasm and star-shaped nucleus as well as holocrine-type secretion.
In apocrine differentiation, a phenomenon called decapitation secretion may be observed. Their characteristic features include excentric nucleus located at the base of the cell and eosinophilic cytoplasmic granules.
The assessment of ductal tumours is significantly more complicated because of the resemblance between the structure of eccrine and apocrine ducts, especially eccrine duct cells that resemble poorly-differentiated apocrine secreting cells [3].
The immunohistochemical phenotype, special staining and the assessment of ultrastructure of cells have secondary importance in terms of defining the origin of adnexal skin tumour. Sebaceous cells present a positive immunohistochemical reaction with low-molecular weight cytokeratin (LMWK), epithelial membrane antigen (EMA) and D2-40. Secretory cells of sweat glands present a non-specific expression of oestrogen and progesterone receptors, LMWK, EMA, carcinoembryonic antigen (CEA) and S-100 have an IHC reaction in eccrine cells and neighbouring myoepithelial cells test positive for smooth muscles actin (SMA), p63 and calponin. Eccrine duct cells react with heavy cytokeratins and cytokeratin 14. Apocrine cells have PAS (+) cytoplasmic granules and iron deposits that change colour reacting with Prussian blue. They also present androgen receptor expression. Luminal cells, on the other hand, have a gross cystic disease fluid protein 15 (GCDFP-15), CEA and EMA expression. Apocrine secretory cells test positive for LMWK, GCDFP-15 and androgen receptor and negative for oestrogen, progesterone and bcl-2 receptors [27, 28].
The most frequently occurring benign tumours originating from skin appendages in OTRs are: syringocystadenoma papilliferum and sebaceous adenoma. The most common malignant tumours are microcystic adnexal carcinoma, hidradenocarcinoma and sebaceous carcinoma (with the most significant malignant potential).

Syringocystadenoma papilliferum

Syringocystadenoma papilliferum is a benign, hamartoma type of tumour of apocrine origin. It grows usually in a form of a solitary, papilliform of brown colour. Clinically it is often marked with a fistula, which oozes brown fluid that sets into a scab. Lesions are usually located within the face and scalp. It develops de novo or stems from naevus sebaceous.
In the microscopic examination, a papillary hyperplasia, covered with two-layer glandular epithelium is a common finding. Papillary lesions expand partially into a cystic, distended area that opens up towards the surface in its central part. Epithelium of the adenoma presents an apocrine-type differentiation [29]. It is very often misdiagnosed as BCC or sebaceous wart.

Adenoma sebaceum

Adenoma sebaceum is a relatively common benign tumour of areas rich in sebaceous glands. They usually present as solitary papules of yellowish colour. They are often scaly, with erosions or scabs. They are primarily situated in the head and neck area, usually in elderly people [30] (Figure 1).
Multifocal lesions develop in OTRs, especially in patients with coexisting Muir-Torre syndrome [31, 32].
Microscopically, it is a lobular structure, compounded of mature sebocytes that are surrounded with a layer of basaloid cells in its peripheral part. The epidermis is segmentally displaced due to the microstructure of the adenoma [29].

Microcystic adnexal carcinoma (MAC)

Microcystic adnexal carcinoma (MAC) is a locally malignant skin tumour with low metastatic potential. It originates from cells differentiating into eccrine glands and hair follicles. Typically it occurs in middle-aged women as a slowly-growing, deeply located nodule or a sclerotic disc of yellowish or erythematous colour, rarely with an ulceration on top. Its characteristic location involves nasolabial groove, cheeks or chin. Uncommonly, it may appear in different spots, like armpits. Clinically it may look benign, which often leads to incorrect diagnoses. In case of a superficial biopsy it may be misdiagnosed as syringoma.
Microscopically it is characterized by the presence of epidermoid cysts (the equivalent of abortive hair follicles), immersed in a thick stroma of connective tissue. Moreover, slim strands of epithelium are commonly found. In deeper parts of the tumour we may observe an intricate network of tiny ducts surrounding blood vessels and nerves. An eccrine-type differentiation is typical [33] (Figure 2).
The tumour grows slowly, widely infiltrating surrounding areas, including subcutaneous tissue, muscles, and nerves. It has a great tendency to relapse. Its differential diagnosis should involve desmoplastic trichoepithelioma and sclerotic-type BCC.
Metastases in immunocompetent patients are extremely rare, however, they are observed more frequently in patients undergoing immunosuppression [30].
So far, 8 cases of this tumour in OTRs have been described in medical journals. One of the most important etiological factors in OTRs is immunosuppression, considering that those cases were reported in patients on immunosuppression. It is claimed that immunosuppressant drugs, especially prednisone, interferes with the structure of the dermis and allows tumour cells to penetrate towards deeper layers of skin [34].

Hidradenocarcinoma

Hidradenocarcinoma usually originates from apocrine glands, less frequently it demonstrates eccrine differentiation. It can develop de novo or transform from a benign lesion called hidradenoma.
Clinically it presents as a solitary, intradermal or subcutaneous nodule. It may be located throughout the skin, however, it usually affects the face or limbs. There is usually no growth in contact with epidermis but in some cases skin covering the lesion may be ulcerated. It occurs more frequently in middle-aged people, slightly more often in female patients. There are some reported cases of this tumour in children [29].
Microscopically, it consists of different, polymorphic epithelial cells that present an increased mitotic activity, abundant cytoplasm with visible clear patches. This tumour may have an aggressive course with local recurrence, which may be accompanied by metastases to local lymph nodes or solid organs. Sporadically they may resemble skin metastases of lung, thyroid or clear-cell renal cancer [2].

Porocarcinoma

Porocarcinoma is the most common malignant adnexal skin tumour. It typically occurs in patients between 40 and 80 years old. Its main locations are lower limbs (50% of cases), trunk (20%), head (15%) and upper limbs (10%). In OTRs, this tumour has a tendency to occur in the head and neck area [2, 35].
Clinically, it presents as nodular or ulcerative laminae or copular tumours of papillary surface and reddish colour. Half of the lesions develop from benign poromas, however in OTRs, de novo development is more common [2]. Aggressive, rapid growth and deep skin infiltration are characteristic for this tumour. Even relatively small tumours may infiltrate lymphatic vessels, metastasise to lymph nodes, followed by lymphatic oedema. The cancer spreads less commonly to lungs or other internal organs. The prognosis in those cases is poor.
Microscopically, it features ductal differentiation. It is compounded of polymorphic basaloid cells with abundant eosinophilic cytoplasm and immature keratinocytes scattered individually or in small groups (Figure 3).
Intraepithelial dissemination at the top of the lesion resembles Bowen’s disease or an irritated sebaceous keratotic lesion, which may lead to misdiagnosis [30]. Differential diagnosis should include above all SCC, BCC and amelanotic melanoma.

Sebaceous carcinoma

Sebaceous carcinoma (SC) is a highly-malignant skin tumour that originates from Meibomian glands, less commonly from glands of Zeis. SC is a rare tumour in immunocompetent people, most of reported cases involved OTRs [7, 36].
Sebaceous carcinoma accounts for less than 1% of all malignant skin tumours and between 1 and 5% of all eyelid tumours. In most cases it affects women aged between 60 and 80, however, it may occur at any age, including childhood [37].
Its clinical picture is diverse. Its usual locations are the head and neck area (especially eyelids), shoulders and trunk. They are usually small, painless, slowly-growing nodules, sometimes with ulcerations or covered with yellowish lamina. Tumour’s growth may cause eyelash loss or vision impairment. Lesions are often misdiagnosed as inflammatory, which delays administering an adequate treatment (Figure 4).
This tumour has a tendency to relapse, which is enhanced by a frequent intraepidermal growth of pagetoid cancer cells, local skin inflammation that blurs the clear border between the tumour and healthy tissue and aggressive local growth with dissemination via blood vessels and nerves. Sebaceous carcinoma may create distant metastases through blood vessels and lymph vessels. The mortality rate is estimated at 22%. Prognosis in patients with metastases is estimated at 50% overall survival within 5 years [29].
In the microscopic examination SC may be misdiagnosed as SCC or BCC. In order to determine a definite diagnosis, findings such as differentiated sebocytes with vacuoles and ductal structures ought to be found. Orbital cancer may present a characteristic, intraepithelial, pagetoid proliferation of tumour cells [30] (Figure 5).
The development of sebaceous carcinoma seems to directly correlate with administering immunosuppressant drugs, above all azathioprine, cyclosporine and prednisone. There are reports of spontaneous regression in patients who were treated with a reduced dose of immunosuppressant drugs. Experimental studies showed that immunosuppressants, especially azathioprine, predispose to developing sebaceous carcinoma.
Based on analyses of SC cases published in medical journals, it may be presumed that patients on immunosuppression are subject to a more severe course of the disease and their prognosis is worse than in the immunocompetent population [2].
In a study conducted by Harwood et al., the presence of increased microsatellite instability and loss of MSH2 protein expression were found in sporadic SC cases in OTRs [7].
Patients’ age also plays a role in SC carcinogenesis. It usually develops in middle-aged and elderly people. The average age of SC diagnosis in OTRs, however, is much lower than in general population.
Radiotherapy also may have an effect on carcinogenesis of this tumour. Patients who underwent radiotherapy as children have a higher incidence of SC. Also, time after transplantation determines the incidence of SC. Eighty percent of patients with SC underwent the transplantation less than 10 years prior to the diagnosis.
Moreover, there were 2 cases of sebaceous carcinoma that were reported by the authors. Case 1 was a 48-year-old female with a history of three kidney transplantations, treated with azathioprine and cyclosporine at the time. She was admitted to the Dermatology Ward with a papillomatous lesion along her right upper eyelid that had appeared 2–3 months prior to hospitalization. The lesion was removed and classified microscopically as sebaceous carcinoma. There were no lymph node metastases. The patient remained under dermatological observation, no recurrence features were noted. Case 2 was an 87-year-old male after kidney transplantation, also treated with azathioprine and cyclosporine. He presented with a lesion on his right temple, which was classified microscopically as sebaceous carcinoma. Metastases were detected in the regional lymph nodes, right parotid gland, right pre-parotid region, right post-auricular area and in the right side of the neck. The patient developed a widespread metastatic disease within 3 years since diagnosis, which resulted in his death [38].
Sebaceous carcinoma is one of conditions presenting in Muir-Torre syndrome, which is an autosomal dominant genodermatosis. It is characterized by presence of multiple, benign and malignant tumours originating from sebaceous glands (especially cystic forms), keratoacanthoma, tumours of organs within the abdominal cavity, most frequently of the gastroesophageal tract. Mutations affect DNA repair genes (MSH2 and MLH1), located on different chromosomes. Hereditary disorders of the same genes are responsible for hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome).
Sebaceous cancer may be the first symptom of MTS. There were several reported cases of this condition in OTRs [4, 39].

Treatment

There is little information in medical journals about prognosis in OTRs who developed adnexal cancer. The prognosis in patients, who had their benign lesions surgically removed, is optimistic. With respect to benign lesions, surgical removal within the border of healthy tissue is usually sufficient. Tumours of low malignancy are usually removed with an ample margin or, when said tumour is relapsing or a good cosmetic effect is important, Mohs surgery is recommended. General rules regarding treatment of highly-malignant tumours such as Merkel-cell carcinoma and melanoma are also in effect when treating the most aggressive adnexal tumour – sebaceous carcinoma. It should be stressed that a multi-disciplinary approach should be applied when dealing with those malignant tumours. Patients should remain under control of many specialists, such as dermatologists, transplantologists, surgeons and oncologists. The therapy of high-risk tumours include surgical excision, sentinel node biopsy, reducing the dose of immunosuppressant drugs or conversion to rapamycin therapy, which has a potential anti-cancer effect. In case of metastases, several chemo- and radiotherapy protocols may be implemented [2].

Other rare skin tumours

There are several types of rare skin tumours that are observed more frequently in OTRs than in the general population of immunocompetent people. Angiosarcoma, malignant fibrous histiocytoma, dermatofibrosarcoma protuberans and leiomyosarcoma may serve as good examples.

Angiosarcoma

Angiosarcoma (AS) is a rare tumour of an unknown aetiology that creates structures resembling blood vessels or lymphatic vessels. Clinical presentation usually involves red-purple patches or tumours developing on the skin of the head, trunk and limbs. Angiosarcoma of the skin and soft tissue usually occurs at the age of 60–70 years old. They are extremely rare in the first decades of life but when they occur, they tend to present greater malignancy than in elderly patients [40].
There were 14 cases of AS of the skin in OTRs (mostly kidney recipients), described in medical journals [41]. The average age at diagnosis was 48 years old (ranging from 31 to 71 years old). In 9 cases they affected males and the tumour occurred on average 6 years following the transplantation. Six tumours were located within or surrounding the arteriovenous fistula created for the purpose of haemodialysis. Other locations of AS involved limbs, scalp and the scar that remained after the transplantation. Despite an aggressive, diverse treatment, the tumours grew rapidly and in 50% of cases caused patient’s death within 7 months from diagnosis. Treatment of AS involves surgical excision and radiotherapy but the results are unsatisfactory [40].

Malignant fibrous histiocytoma/ undifferentiated pleomorphic sarcoma

Malignant fibrous histiocytoma (MFH) is considered to be the most frequent soft-tissue sarcoma. It manifests as a pathological mass occupying the subcutaneous tissue or internal organs. It appears as a tumour, sometimes with ulceration, resembling SCC or BCC. Its origin may be linked to an increased exposure to UV-radiation and with TP53 gene mutations. MFH tends to occur more frequently in OTRs than in general population. There were 10 cases of this malignancy described in patients undergoing immunosuppression – 8 in kidney transplant recipients and 2 in heart transplant recipients. All patients were males at the average age of 58 years old. The most common location were the head and neck, followed by upper and lower limbs. Despite the surgical treatment, relapses and metastases were frequently observed. An unfavourable course of the disease was observed in 2 patients with MFH [36]. A surgical excision of the lesion is the preferred treatment (similar to SCC). The alternative therapeutic option is neoadjuvant chemotherapy based on methotrexate.

Dermatofibrosarcoma protuberans

Dermatofibrosarcoma protuberans (DFSP) is the most frequently occurring skin sarcoma. It usually develops in young adults and manifests clinically as a sclerotic, brown disc that gradually evolves to become a multi-nodular lesion. Its pathogenesis is unknown. It is characterized by the presence of t(17;22) translocation in which the fusion gene COL1A-PDGFB is created. Dermatofibrosarcoma protuberans usually presents local malignancy during transformation to fibrosarcomatous variant but it may metastasise, primarily to lungs. There were 3 reported cases of DFSP in patients on immunosuppression. They all involved kidney transplant recipients. The patients were 34, 45 and 61 when diagnosed. They were located on the cheek, arteriovenous fistula and on the hand. All lesions were removed, effecting a complete cure [36].

Leiomyosarcoma

Leiomyosarcoma (LMS) is a malignant condition with smooth-muscle differentiation. Several cases of LMS were observed in patients who underwent transplantation, especially children. LMS is linked to the activation of the EBV virus. Skin-type LMS features a solitary, sclerotic nodule or disc, located usually on lower limbs. The cause of LMS is unknown, despite cases of LMS with prior trauma, radiation or pre-existing myomas. Skin-type LMS is linked to better prognosis than deeper lesions. In spite of that fact, local relapse and remote metastases may be observed.
So far, there have been 3 cases of skin-type LMS in kidney recipients described in medical journals. One patient required an amputation due to the advanced stage of the tumour. Another patient died due to metastases [40]. Treatment of LMS usually involves surgical excision with a 2–5 cm margin of healthy tissue.

Summary

Rare skin tumours in OTRs are not frequently observed when compared to epidermal tumours. Some of them occur significantly more frequently in OTRs than in immunocompetent population.
The most commonly described benign tumours are adenoma sebaceum and syringocystadenoma papilliferum. So far there have been 46 cases of invasive adnexal tumours in OTRs described in medical journals. Two cases of sebaceous carcinoma come from authors’ own observations, resulting in a total of 48 cases. The most common tumour diagnosed in OTRs is sebaceous carcinoma – there were 21 case reports.
Most frequently-occurring malignancies, originating from mesenchymal tissue, are angiosarcoma and malignant fibrous histiocytoma. They are rarely observed in OTRs.
It is also worth mentioning that these tumours may present clinically as benign lesions, which may lead to an incorrect diagnosis. This may result in patient’s disability or death. It is of the utmost importance that the medical staff who treat OTRs should be aware of the existence of these tumours and how they present clinically and microscopically.

Conflict of interest

The authors declare no conflict of interest.
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