Vol.

43 (2): 202-208, March - April, 2017

ORIGINAL ARTICLE
doi: 10.1590/S1677-5538.IBJU.2015.0665

Diagnostic relevance of metastatic renal cell carcinoma in

the head and neck: An evaluation of 22 cases in 671 patients
_______________________________________________
Anja Lieder 1, Thomas Guenzel 2, Steffen Lebentrau 3, Constanze Schneider 4, Achim Franzen 1
1
Department of Otorhinolaryngology, Ruppiner Kliniken and Brandenburg Medical School Theodor-
Fontane, Neuruppin, Germany; 2 Department of Otorhinolaryngology, Head and Neck Surgery,
Borromaeus-Hospital Leer Germany; 3 Department of Urology and Pediatric Urology, Ruppiner Kliniken
and Brandenburg Medical School Theodor-Fontane, Neuruppin, Germany; 4 Clinical Cancer Registry
Brandenburg, Neuruppin, Germany

ABSTRACT ARTICLE INFO

______________________________________________________________ ______________________

Purpose: Renal cell carcinoma (RCC) is a malignant tumor that metastasizes early, and Keywords:
patients often present with metastatic disease at the time of diagnosis. The aim of our Carcinoma, Renal Cell; Neoplasm
evaluation was to assess the diagnostic and differential diagnostic relevance of meta- Metastasis; Carcinoma,
static renal cell carcinoma (RCC) with particular emphasis on head and neck manifesta- squamous cell of head and neck
tions in a large patient series. [Supplementary Concept]
Patients and methods: We retrospectively evaluated 671 consecutive patients with RCC
who were treated in our urology practice between 2000 and 2013. Int Braz J Urol. 2017; 43: 202-8
Results: Twenty-four months after diagnosis, 200/671 (30%) of RCC had metastasized.
Distant metastases were found in 172 cases, with 22 metastases (3.3%) in the head and _____________________
neck. Cervical and cranial metastases were located in the lymph nodes (n=13) and in Submitted for publication:
the parotid and the thyroid gland, tongue, the forehead skin, skull, and paranasal si- December 22, 2015
nuses (n=9). All head and neck metastases were treated by surgical excision, with 14 _____________________
patients receiving adjuvant radiotherapy and 9 patients receiving chemotherapy or Accepted after revision:
targeted therapy at some point during the course of the disease. Five patients (23%) June 29, 2016
survived. The mean time of survival from diagnosis of a head and neck metastasis ________________________
was 38 months, the shortest period of observation being 12 months and the longest Published as Ahead of Print:
83 months. September 20, 2016
Discussion and conclusion: Our findings show that while RCC metastases are rarely
found in the neck, their proportion among distantly metastasized RCC amounts to
13%. Therefore, the neck should be included in staging investigations for RCC with
distant metastases, and surgical management of neck disease considered in case of re-
sectable metastatic disease. Similarly, in patients presenting with a neck mass with no
corresponding tumor of the head and neck, a primary tumor below the clavicle should
be considered and the appropriate staging investigations initiated.

INTRODUCTION commonly, metastases occur in lung, bone or li-

ver and often in multiple sites (1). Head and neck
Renal cell carcinoma (RCC) is a malignant metastases are rare but there is little evidence in
tumour of the kidney that metastasizes early. Most the literature as to their pattern and management.

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 ibju | Renal Cell Carcinoma Metastases of the Head and Neck

Numerous single case reports and small RCC, with an additional 13% (89/671) diagnosed
series of metastasis of RCC into the head and following treatment.
neck region are available in the literature. These Distant metastases were found in 172 pa-
case reports focus mainly on particular, unusual, tients (26%), and regional lymph node metastases
and especially extranodal location of the metas- in 22 patients (3%). In 92 patients (14%), metasta-
tases as well as unusual clinical courses (2-8). ses were identified at the time of diagnosis of the
The aim of this study was to assess the differen- primary tumour, and in the remaining 80 patients
tial diagnostic and also the therapeutic relevance (12%) metastasis occurred over the course of the
of metastatic RCC in a large series of RCC and to following 24 months despite curative intent treat-
evaluate if a systematic examination of the head ment (Table-1).
and neck is appropriate in the context of staging Metastases of RCC in the head and neck
RCC. We present an analysis on RCC metastasi- were found in 22 patients (3%). Sixteen patients
zing into the head and neck region based on a were male and six were female. The mean age
large group of 671 consecutive patients with an of these patients at the time of diagnosis was 66
RCC treated in our unit. years (32-81 years). In 10 patients (45%), head and
neck metastases appeared simultaneously to the
PATIENTS AND METHODS primary tumour, or the metastasis was the first
manifestation of the RCC. In 12 patients (55%),
Medical records of 671 consecutive pa- metastases were detected at follow-up following
tients who were diagnosed with an RCC in the De- curative intent treatment after 24 months on
partment of Urology of Ruppiner Kliniken, a large average. The longest period between treatment of
District General Hospital, between 2000 and 2013 the primary RCC and the detection of metastases
were evaluated. All patients were followed-up un- in the Head and Neck was 87 months.
til the time of their death; surviving patients were The histological type of renal cell carci-
followed-up for at least 24 months from the date noma was clear cell renal carcinoma in 14 cases,
of diagnosis. All data were collected from case poorly differentiated or undifferentiated carcino-
notes, anonymized and maintained in an Apache ma in six cases, nephroblastoma in one case and
OpenOffice4 database and analyzed using a sta- small cell renal carcinoma in one case. Tumour
tistical software package (Apache OpenOffice4 Grade was G2 in 8 cases, G3 in 9 cases, and un-
Calc with R4Calc R extension). As this study was determined in 5 cases. Initial TNM stages ranged
a retrospective case notes study, formal ethical from T1N0M0 to T3N2M1 at the time of diagnosis.
approval was not required. Written consent was Metastases to cervical lymph nodes were
obtained from all patients prior to undertaking found in 12 out of 22 cases. Organ metastases
any procedures but for this retrospective case note were found in the parotid (n=1) and thyroid gland
audit, formal written consent was not required. (n=3) and skull bone (n=2). Other locations (n=3)
All investigations and treatments were carried out included the tongue, facial skin and frontal sinus
according to accepted clinical practice and were (Figure 1). Recurrence in context of a metachronous
compliant with the medical principles of the Dec- cervical metastasis was seen in one case. In 19
laration of Helsinki. out of 22 patients, synchronous disseminated
metastases were detected in other organs at
RESULTS some stage during the course of the illness. In 10
patients, this occurred simultaneously with the
Of 671 consecutive patients diagnosed with head and neck metastases. The most important
RCC, 200 (30%) had distant or regional lymph metastatic target organs in these 19 cases were
node metastases either at the time of diagnosis the lung (n=12) and the skeletal system (n=9).
or within 24 months of diagnosis. The overall Other less frequent locations were the liver, the
metastatic rate, including locoregional metastases, brain, and the peritoneum. In 3 out of 22 patients,
was 17% (111/671) at the time of diagnosis of metastasis occurred solely in the head and neck.

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 ibju | Renal Cell Carcinoma Metastases of the Head and Neck

Table 1 - Patient and tumour characteristics.

No. Age * Histology Grade TNM at primary Time to Location Other metastases Management of Survival after Metastasis

diagnosis management Metastasis ** Metastasis metastatic disease (H&N) in months

1 70 clear cell 2 pT2bpNxM1 nephrectomy 0 Level IV Lymph Lung, bones Excision 2

node
2 58 clear cell 2 pT3apN0M1 nephrectomy 5 Thyroid Gland Retroperitoneum, pancreas Excision 24 (patient alive)

(Thyroidectomy),
Sunitimib
3 74 clear cell *** unknown nephrectomy 78 Parotid Gland none Excision 56 (patient alive)

(Parotidectomy),
4 52 clear cell/poly 3 pT3pN2 M1 nephrectomy 5 Level IV Lymph Lung, bones Excision, radiotherapy, 14

node chemotherapy
5 78 clear cell 2 pT2NxM1 nephrectomy 65 Frontal Sinus Brain, lung, bones, liver Radiotherapy 2
6 69 undifferentiated 3 cT3cN1cM1 chemotherapy 0 Level IV Lymph Bone, liver, peritoneum Excision, radiotherapy, 14

node chemotherapy
7 73 clear cell 2 pT1bNxMx nephrectomy 94 Level IV Lymph Lung, bones Excision, radiotherapy, 7

node chemotherapy,

Sorafenib
8 69 clear cell 3 pT1cN0cM0 nephrectomy 14 Level IV Lymph Peritoneum Excision, radiotherapy 4

node
9 70 undifferentiated *** TxN1M1 chemotherapy 0 Level IV Lymph Lung, mediastinum Chemotherapy, 28

node Sunitimib
10 69 undifferentiated *** pT3cN0cM1 nephrectomy 24 Level IV Lymph Lung, bones, liver, adrenal Excision, 12

node glands chemotherapy,

Sunitimib
11 32 Nephroblastoma 3 pT3bpN0cM1 nephrectomy 0 Level IV Lymph Lung, liver Chemotherapy, 24

node radiotherapy

(other centre)
12 56 clear cell 3 pT3acN1cM1 nephrectomy 5 Tongue Lung, bones, mediastinal Excision (glossectomy), 3

nodes, soft tissue finger radiotherapy

13 66 polymorph 3 pT1bNxMx nephrectomy 75 Frontal Skull Lung, bones, soft tissue Sunitimib, 13

bone back chemotherapy

radiotherapy
14 81 undifferentiated *** unknown declined treatment 0 Level IV Lymph none Declined treatment 0

node
15 69 clear cell 2 pT1acNxM0 nephrectomy 69 Level IV Lymph Retroperitoneal lymph Excision, chemotherapy 19

node nodes (paraaortal)

16 68 clear cell 2 pT1bpN0cM0 nephrectomy 36 Facial Skin Lung, adrenal glands, Excision 19 (patient alive)

(forehead) jejunum
17 48 clear cell 2 pT1bN0M0 nephrectomy 87 Thyroid Gland Lung, bones, mediastinum Excision, laminectomy, 27 (patient alive)

adrenalectomy chemotherapy,

Sunitimib
18 72 small cell *** cT4cN1M1 resection 0 Frontal Skull Lung, brain, mediastinal Excision, radiotherapy 13

metastasis bone and lymph nodes

mandible
19 73 clear cell 2 pT1a cN0 M1 nephrectomy 40 Thyroid Gland Lung, bones, mediastinum Excision, radiotherapy 86 (patient alive)
20 78 clear cell 3 pT2bNxM0 nephrectomy 6 Level IV Lymph Lung, retroperitoneum Excision, Sunitimib 7
node
21 63 undifferentiated *** unknown nephrectomy 0 Level IV Lymph Lung Excision, none to lung 2

node
22 65 undifferentiated *** unknown unknown unknown unknown unknown unknown Lost to follow up

*Patient age at the time of head and neck metastasis

**Time from first diagnosis of RCC to head and neck metastasis in months
***Tumour Grade undetermined

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 ibju | Renal Cell Carcinoma Metastases of the Head and Neck

Figure 1 - Distribution of head and neck metastases by location (in % of n=22 patients).

Distribution of Head and Neck Metastases

48.0

14.0 14.0
10.0

5.0

level IV NODES THYROID PAROTID SKULL BONE OTHER

All 22 patients received curative intent tre- performed in one patient, following resection of
atment at the time of diagnosis, except for one pa- the head and neck metastasis in 4 cases, and follo-
tient, who declined treatment. Eighteen patients, wing detection of other metastases in 9 cases. The
all of whom had the primary tumour diagnosed dose of radiotherapy was 40 Gray except in four
first or synchronous with the head and neck me- patients who requested palliative treatment; 25
tastasis, received a nephrectomy. Gray were administered in such cases.
In the 18 cases where metastases in the Chemotherapy was performed in 9 pa-
head and neck were found after diagnosis of the tients, usually following the diagnosis of dissemi-
primary tumour or at staging of the primary tu- nated metastatic disease. Due to the long observa-
mour, patients received curative intent treatment tion period, chemotherapy regimens changed over
at the time of initial diagnosis and were then time and included both standard chemotherapy,
followed-up by either a hospital or community chemoimmunotherapy and targeted therapy. In
urology tumour surveillance programme. particular, targeted therapy with either Sunitinibe
Nephrectomy was performed in 17 pa- or Sorafenibe was given to 6 patients.
tients, total nephrectomy in 13 patients and par- Sixteen patients (73%) with head and neck
tial nephrectomy in 4 patients. When metastases metastases died from RCC. The time of death was
of the head and neck occurred, they were treated on average 25 months after an RCC was first diag-
by surgical resection and adjuvant radiotherapy. nosed, and 13 months after diagnosis of a head
In the 10 patients where diagnosis of the RCC and neck metastasis. The median survival time
head and neck metastasis preceded (4 patients) after a RCC was first diagnosed was 28 months,
or coincided (6 patients) with diagnosis of the meaning that 11 patients (50%) were still alive
primary tumour, patients received surgical treat- at 28 months after their RCC was diagnosed. The
ment of the head and neck metastasis first follo- median survival time after diagnosis of a head
wed by surgery to the primary tumour followed and neck metastasis was 13 months. Patients died
by adjuvant radiotherapy. from either disseminated disease or local recurren-
Radiotherapy was performed in 14 cases. ce with the exception of one case, who died from
Radiotherapy after primary tumour resection was an acute event.

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 ibju | Renal Cell Carcinoma Metastases of the Head and Neck

Five patients (23%) survived and one early stage (61% in stage I) and had been well
patient was lost to follow-up. The mean time differentiated (Grade 1 + Grade 2: 68%).
of survival from diagnosis of a head and neck RCC are considered to be the third most
metastasis was 38 months, the shortest period frequent infraclavicular tumour metastasizing to
of observation being 12 months and the lon- the head and neck. Supraclavicular metastases
gest 83 months (standard deviation 30 months) were found in 3% (22/671) of all our patients with
(Figure-2). RCC. In the literature, there are reports of metasta-
tic rates of up to 15% (3-6). Whether these results
DISCUSSION can be compared to those presented here, remains
to be discussed with regards to size of study, stage
RCC are slowly growing, capsule-forming of disease, duration of follow-up and whether all
tumours and most frequently metastasize into patients were staged specifically for metastases of
lung and the lymph nodes, followed by the ske- the head and neck.
letal system and the liver – in the majority of the While the proportion of RCC metastasizing
cases, several organ systems are affected simulta- to the head and neck was low at 3%, we observed
neously (1). The metastatic rate of 17% (111/671) head and neck metastases in 11% (22/200) of all
in our patient group at the time of diagnosis, and metastasized RCC and in 13% (22/172) of all dis-
an additional 13% (89/671) in the further course tantly metastasized RCC.
of the disease, is lower than described in other According to our results, RCC metastasizing
studies (2). This could be explained by the fact into the head and neck area primarily metastasize
that 66% of our cases had been diagnosed in an into the cervical lymph nodes. In the literature,

Figure 2 - Survival after diagnosis of a head and neck metastasis, shown in months with standard deviation.

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

Survival after H+N Metastasis Survival after RCC First Diagnosis

0.1

0
0 6 12 18 24 30 36

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 ibju | Renal Cell Carcinoma Metastases of the Head and Neck

there are several reports about unusual manifestations other locations. Appropriate staging procedu-
of RCC in different organs of the head and neck. res would include imaging of the neck by either
Single case observations refer to the parotid gland, computed tomography (CT) or magnetic resonan-
the skull, the skin, the oral cavity, and the paranasal ce imaging (MRI) with contrast and, if upper ae-
sinuses (3, 5-10), which were also seen in our patient rodigestive tract symptoms are present, a laryn-
group. Two large multicentre studies also reported go-pharyngoscopy.
metastatic spread of RCC into the thyroid gland, a Surgery as therapeutic option of metasta-
phenomenon that was also observed in two of our sized RCC has an great significance. Good onco-
patients (10, 11). logic clearance is achieved in particular if metas-
Our observations also show the variable pat- tases occur more than two years after treatment
tern of cervical metastasis of RCC. In some cases, a of the primary tumour, and where there is good
cervical metastasis may represent the first mani- surgical access. This applies to large case series
festation of an RCC, in other cases, cervical me- on treatment outcomes of lung and liver metas-
tastases may occur months or years after curative tases of RCC (15-17), and international guidelines
intent treatment of an RCC (5, 6, 12). In 3 out of recommend surgical therapy of metastases despi-
22 patients, a solitary cervical lymph node metas- te improvements of chemotherapy outcomes (2).
tasis was the first manifestation of a previously Larger series of surgical therapy of supraclavicular
unknown RCC. At the other end of the spectrum, a metastases have only been published for patients
solitary metastasis appeared in the parotid gland 6 with thyroid gland metastases. The five-year sur-
years after diagnosis of the primary tumour. In the vival rate of those patients amounted to 51% (10,
other 19 patients, the metastatic spread of the RCC 11). Only case reports only exist about the surgical
into the head and neck occurred at the same time therapy of RCC metastases in other supraclavicu-
as metastasis into other organ systems. lar locations. Curative therapeutic options exist in
Lymph node metastases and metastases of cases of single metastasis into the head and neck
the parotid gland generally occur as painless, re- (7, 8), but surgical management of head and neck
latively slowly growing tumours (7, 9, 13). Facial metastases can also be appropriate for symptom
nerve palsies in conjunction with parotid metas- control in cases of airway obstruction, haemor-
tasis of a RCC are rare (3). Metastases within the rhage, or pain (13). We observed survival of 23%
upper aerodigestive tract such as the oral cavi- of patients with a head and neck metastasis follo-
ty and the pharynx are often painful. They are wing treatment, and would therefore have no he-
usually diagnosed when patients present with sore sitation in recommending curative intent manage-
throats or oral pain, and grow nearly always sub- ment of head and neck metastases in all patients
mucosally, show signs of increasing vasculariza- fit for surgery.
tion and are often distinguished from mucosa by
their red discolouration. Such lesions will bleed CONCLUSIONS
profusely when biopsied or haemorrhage spon-
taneously, and life-threatening haemorrhage has Our results show that 3% (n=22) of all
been reported. Metastases in the supraglottic la- patients with an RCC (n=671) treated in our unit
rynx may cause narrowing of the upper airway, developed metastatic disease into the head and
stridor and dyspnoea. Manifestations of the nasal neck. This accounts for 9% of metastasized RCC.
cavity or the paranasal sinuses lead to nasal obs- It remains open for discussion whether inclusion
truction, sinusitis-like complaints, or significant of the head and neck into the staging procedure
haemorrhage (14). should be recommended – it should, however, be
According to our observations, the head considered in all cases of metastasized RCC. It
and neck were involved in 13% of distantly me- is also of note that head and neck metastases of
tastasized RCC. This must be considered in pa- RCC may occur at any time during the course of
tients who are due to undergo extensive surgery the illness and any patient reports of head and
of either the primary tumour or metastases in neck-related symptoms such as neck swelling,

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 ibju | Renal Cell Carcinoma Metastases of the Head and Neck

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