Epithelial-myoepithelial parotid carcinoma after kidney transplantation
R Horta1,2, F Barreto1,2, M Marques1,2, M Rebelo1,2, JC Reis1,2, JM Lopes1,2 and JM Amarante1,2
1Department of Plastic, Aesthetic, Reconstructive, Maxilo-Facial Surgery, and Burn Unit, Hospital de São João, Porto, Portugal
2Department of Pathology, Porto Medical Faculty, Hospital de São João and IPATIMUP, Porto, Portugal
Correspondence to Ricardo Horta. Email: firstname.lastname@example.org
The occurrence of a second malignant neoplasm (SMN) in patients who have been submitted to kidney transplantation is increasing and
causes concern; parotid carcinoma is rarely reported after transplantation and may be related to long-term chemotherapy.
Salivary gland carcinomas displaying exclusively myoepithelial differentiation—myoepithelial carcinomas (EMC) are rare, being less than
1% of all salivary gland tumours. EMC arises most commonly in the parotid gland and usually occurs in women. Their histopathologic
features, immunohistochemical profile and clinical behaviour remain controversial.
Published: 21/08/2008 Received: 25/06/2008
ecancer 2008, 2:92 DOI: 10.3332/ecancer.2008.92
Copyright: © the authors; licensee ecancermedicalscience. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction
in any medium, provided the original work is properly cited.
ecancer 2008, 2:92
We here report a case of EMC occurring in a 74-year-old man, 14 years after chemotherapy (azathioprine and cyclosporine), following
kidney transplantation due to chronic renal failure (hypertensive cause).
The incidence of cancers after renal transplantation is significantly higher than in the general population. It is increased by long-term
immunosuppressive therapy  required to maintain the functional graft. The chronic use of immunosuppressive therapy in transplant
recipients to prevent acute rejection increases the long-term risk of cancer. The overall incidence of de novo malignancies (DNM) after
kidney transplantation ranges from 6% to 11%.
The patient was followed up in the Plastic Surgery Department due to the presence of multiple malignant cutaneous neoplasms. In April
2005, he underwent excision of a scalp lesion, which was repaired with a split graft, and in January 2007, a forehead neoplasm was
removed and two V-Y advancement flaps were used to cover the wound. Both lesions were epidermoid carcinomas.
In August 2007, the patient presented a left parotid swelling: fixed, solid and painless, which had been growing for two months, without
signs of peripheral facial palsy.
Computed tomography scan (CTS) of the maxillofacial area showed a solid 36 × 20 mm mass, in the left parotid gland (Figure 1).
A few small ipsilateral infra-centrimetic jugulocarotid nodes were detected, without contralateral or other salivary gland alterations
(Figure 2). Fine-needle aspiration of the parotid mass was not diagnostic.
A whole body bone scintigraphy scan did not show focal or distant metastatic disease.
The patient underwent a total left parothyroidectomy (Figure 3), preserving the main branches of the facial nerve except the cervical
branch due to direct invasion, and to a homolateral supraomohyoid dissection.
Histologically, the mass was a carcinoma measuring 3 x 1.8 x 1.3 cm, well circumscribed and with a fibrous capsule. It was composed
almost entirely of epithelioid cells with abundant clear cytoplasm and a predominantly solid pattern with hyaline extracellular matrix. The
tumour cells invaded lymphatic type vessels but not the perineurial spaces. PAS staining showed positive cytoplasmic material that was
diastase sensitive, that is glycogen type. One out of 36 lymph nodes (mid-jugular) showed metastatic cells. The remaining parenchyma
presented with chronic inflammatory lesions.
The tumour cells expressed AE1/AE3, p63 and 34bE12 in absence of immunoreactivity for S100 protein, CD10 and CEA. These features
(Figure 4) were consistent with the diagnosis of epithelial-myoepithelial carcinoma, clear-cell type, pT3, N1, M0, R2.
The patient experienced transient facial nerve paresis and underwent post-operative radiotherapy. Six months later, in follow-up, there is
no sign of carcinoma recurrence.
At the present time, he is in ophthalmological follow-up because of facial nerve paresis.
Until recently, EMC was barely recognized. In 1985, Barnes et al reviewed the literature of all myoepitheliomas of the head and neck and
found only three cases. Dardick et al [3–5] reported in 1989 and in 1995 features of the variable patterns and proposed myoepithelial
carcinoma as a novel histological type of salivary gland tumours. Nevertheless, the spectrum of histological and immunohistochemical
features of ECM as well as adequate treatment regimes remain controversial.
ecancer 2008, 2:92
Figure 1: Cervical TC scan
Figure 2: Left parotid swelling
ecancer 2008, 2:92
A recent study  summarizing new findings on salivary gland pathology has included the morphological spectrum of epithelial-myoepi-
thelial carcinoma and variants.
(1) Oncocytic variant with extensive oncocytic change in the luminal cells or in both the luminal and abluminal cells. Some of these cases
may show a prominent papillary growth pattern and may mimic sebaceous type differentiation.
(2) The double-clear variant with clear cell change in the abluminal myoepithelial cells, but also in luminal cells. When the epithelial
component showing solid or cribriform architecture, it can be difficult to distinguish morphologically epithelial and myoepithelial cell
The myoepithelial component in epithelial-myoepithelial carcinoma can exhibit ‘ancient change’, that is enlarged, hyperchromatic nuclei.
In contrast to de-differentiation or high-grade transformation, the chromatin is smudged. Cytological atypia is random and mitotic activity
Epithelial-myoepithelial carcinoma exhibit two forms of progression:
(1) overgrowth of the myoepithelial component with nuclear anaplasia. This phenomenon is also described as epithelial-myoepithelial
carcinoma with myoepithelial anaplasia, when nuclear atypia in >20% of the myoepithelial cells;
(2) de-differentiation to high-grade carcinoma without evidence of myoepithelial differentiation. The de-differentiated component shows
high mitotic activity, and necrosis is common. They display a high recurrence rate.
Epithelial-myoepithelial carcinoma, despite the not infrequent presence of aggressive histological features, is a low-grade tumour that
rarely metastasises or causes death. The most important predictive recurrence factors are surgical margin status, angiolymphatic inva-
sion, tumour necrosis and myoepithelial anaplasia. High Ki-67 proliferative index, solid growth, size and perineural invasion all seem to
significantly impact on patient survival.
In this particular case, however, we have seen an aggressive tumour with lymph-node invasion; there was no evidence of any recent skin
carcinoma (previously common in this renal transplanted patient), and the histopathology revealed that the lymph-node metastasis was
from the parotid carcinoma.
Figure 3: Operative view: left parotidectomy
ecancer 2008, 2:92
Due to the limited experience in the treatment of EMC, complete excision is the therapy of choice. EMC should be excised surgically with
cervical lymph node dissection; post-operative radiotherapy and chemotherapy can be used but do not prevent the high rate of recur-
rence. Thus their use has still to be established. Metastatic sites include kidney, lung, brain, cervical lymph nodes, ribs and the scalp .
The NCCN guidelines  state that only salivary gland cancer patients with more than stage T1 disease should undergo radiotherapy
(RT); this is also true for completely excised tumours with positive or close margins, intermediate or high grade, perineural or vascular
invasion and lymph node metastasis. The exception is adenoid cystic carcinomas that require RT also at stage T1.
Due to their rarity, pathogenesis and consensus therapeutic guidelines are still elusive .
Seethala et al found that surgical margin status, angiolymphatic invasion, necrosis and myoepithelial anaplasia were the most significant
predictors of survival .
An increasing number of kidney transplant patients, and the associated long-term treatment with multiple-agent chemotherapy, requires
long-term follow-up with regular physical and imaging examinations. Surgeons and oncologists should be aware that second malignant
Figure 4: Clear cell myoepithelial carcinoma
ecancer 2008, 2:92
neoplasm (SMN) to organs rarely susceptible to metastasis, such as the parotid gland, may occur even in patients not given radiotherapy
to the head and neck region [11,12].
Immunosuppressant drugs used in organ transplantation such as cyclosporin (CiP) increase the susceptibility to infections, neoplasia
and hypersensitivity reactions to drugs. The dose-dependent side effects are arterial hypertension, hypomagnesaemia, hyperuricemia,
peripheral neurological symptoms, hyperlipidemia and gastric intolerance [12–15]. The main adverse cutaneous manifestations are hyper-
trichosis, epidermal cysts, fibrotic gingival hyperplasia and keloid folliculitis.
Regarding carcinogenesis, there is a high tendency toward the development of neoplasms, particularly lymphoid (relative risk 28 times
greater than in the general population) and cutaneous lesions, related to the high doses and long-term therapy with immunosupressants
and exposure to ultraviolet radiation. The cutaneous neoplasms most frequently described are epidermoid carcinoma, basal cell carci-
noma, Kaposi’s sarcoma, Bowen’s disease and melanoma.
Other immunosuppressive agents also strikingly increase the risk of neoplasia, but the latency period for carcinogenesis is shorter with
CiP . There is a report of one case of pityriasis rubra pilaris and carcinoma of the parotid associated with CiP, retinoids and PUVA
In vitro studies on azathioprine have shown the development of chromosomal anomalies in pharmacological but not in therapeutic doses.
Azathioprine was associated with higher incidence of cutaneous tumours, non-Hodgkin lymphomas, vulvar and cervical carcinoma, and,
in association with corticosteroid treatment of kidney transplant patients, with Kaposi’s sarcoma . The estimated incidence of tumours
in these patients is 1–8%. It seems that there is no increase risk for other tumours in other locations, for example lung, breast, colon and
Maanziti et al  described a case of parotid carcinoma after autologous bone marrow transplantation for relapsed nephroblastoma and
suggested this association with renal fossa radiation, especially when associated with multiple agent chemotherapy (doxorubicin, vincris-
tine, actinomycin D).
We report a rare case of epithelial-myoepithelial parotid carcinoma after kidney transplantation, associated with double agent
Figure 5: Results after 1 year
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The increased risk for SMN may be dependent on a combination of genetic susceptibility, irradiation and anti-neoplastic treatment. The
low risk in non-transplanted patients is probably related to the use of low doses and shorter treatments and to the absence of chronic
antigenic stimulus by the transplanted organ .
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