A case of tongue cancer in which it was difficult to distinguish
cervical lymph node metastasis owing to post-treatment Hodgkinʼs
lymphoma recurrence versus tongue cancer metastasis
Yu Ohashi1,2), Katsunori
Katagiri2,3), Daisuke Saito2,3),
Shin-ichi Oikawa2,3), Kodai
Tsuchida2,3), Jun Miyaguchi2,3),
Takahiro Kusaka2,3), Hiroyuki
Yamada1,2), Kiyoto Shiga2,3)
- Division of Oral and Maxillofacial Surgery, Department of
Reconstructive Oral and Maxillofacial Surgery, Iwate Medical
University, School of Dentistry, Morioka, Japan
- Head and Neck Cancer Center, Iwate Medical University Hospital,
Yahaba, Japan
- Department of Otolaryngology-Head and Neck Surgery, Iwate Medical
University, School of Medicine, Yahaba, Japan
Abstract
We report a case in which it was difficult to distinguish cervical lymph
node involvement from Hodgkinʼs lymphoma vs cervical lymph node
metastasis from tongue cancer. Additionally, we report the
histopathology for a postoperative follow-up biopsy of an enlarged lymph
node in this patient with Hodgkinʼs lymphoma in remission.
1. Introduction
Cervical lymph node metastasis in oral cancer is often seen in the
ipsilateral levels I, II, and III nodes, and skip-like metastasis to
levels IV and V without metastasis in levels I‒III is very
rare.1 To the best of our knowledge, there have been
no reports of oral cancer that metastasized only to the contralateral
cervical lymph nodes, with no metastasis to the cervical lymph nodes on
the affected side. We report a case of tongue cancer that metastasized
only to the contralateral cervical lymph node after treatment for
Hodgkinʼs lymphoma, with a primary lesion in the ipsilateral cervical
lymph node.
2. Case history and examination
The patient was a 74-year-old man. He had been aware of intractable
stomatitis on the apex of his tongue for 1 year prior to his visit to
our center. One month prior to his visit, an ulcer was observed in the
same area; therefore, he visited a dental clinic. He was referred to our
center because tongue cancer was suspected. He had received six courses
of doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine
for Hodgkinʼs lymphoma (mixed cell type, stage II) between 1 year and 6
months previously, which had remained in remission (Figure 1). He also
had hypertension and dyslipidemia, and he had smoked 20 cigarettes per
day from age 20 to 74 years. He drank a small amount of alcohol, was
Flusher, and had no remarkable family medical history. He was 164.7 cm
tall, weighed 63.5 kg, and had normal nutritional status. Two mobile,
non-tender lymph nodes measuring 10 mm in the longest diameter were
palpated in the left submandibular region. A tumor with ulceration and
surrounding induration with the longest diameter of 26 × 20 mm was
observed on the right tongue (Figure 2). And the tongue tumor was
biopsied and found to be squamous cell carcinoma. Panoramic X-ray
findings showed that the proximal roots of 44‒46 were intact, and a
dental implant was present in the equivalent area of 47. Bone resorption
was seen around the remaining tooth, and diffuse osteosclerosis was also
seen in the surrounding area (Figure 3). Computed tomography showed a 24
× 19.3 × 14.2-mm, large, contrast-enhanced tumor extending from the
right lingual apex to the edge of the tongue, with the center of the
tumor depressed. Hypo-absorption of contrast was seen in the left level
IB and III lymph nodes (Figure 4). Magnetic resonance imaging revealed a
contrast-enhanced 23.4 × 19.6-mm, large tumor with a depth of invasion
(DOI) of 13.9 mm extending from the right lingual apex to the edge of
the tongue (Figure 5). Fluorodeoxyglucose positron emission
tomography/computed tomography revealed a tumor with abnormal
accumulation and with a maximum standardized uptake value of 14.46 at
the right lingual border. Additionally, enlarged lymph nodes were seen
at left levels IB and III, with abnormal accumulation and maximum
standardized uptake values of 4.10 and 9.00, respectively (Figure 6). No
remarkable abnormalities were noted in the blood examination findings
for both general blood tests and biochemical tests.
The tongue tumor was biopsied, and histopathology revealed a
well-differentiated squamous cell carcinoma. Imaging of the lymph nodes
at left levels IB and III was unclear regarding
whether the changes in these lymph nodes indicated metastases of the
tongue cancer or recurrence of Hodgkinʼs lymphoma. Preoperative
examination results were evaluated as tongue cancer, cervical lymph node
metastasis (cT3N2cM0), or tongue cancer (cT3N0M0) and recurrent
Hodgkinʼs lymphoma.
3. Treatment
After considering left-sided levels IB and III lymph node fine needle
aspiration cytology or lymph node biopsy, it was decided that
glossectomy and prophylactic neck dissection of the right cervical lymph
nodes were indicated for the cT3 tongue cancer. We planned bilateral
cervical dissection if squamous cell carcinoma was detected in the right
cervical lymph nodes. If Hodgkinʼs lymphoma was detected in the right
cervical lymph nodes, right-sided neck dissection was planned.
Surgery was performed on the basis of the results of a biopsy of an
enlarged lymph node at left level IB. This lymph node was identified as
metastatic squamous cell carcinoma on rapid diagnosis; therefore,
bilateral neck dissection was performed. Right-sided neck dissection was
performed as prophylactic neck dissection with supra-omohyoid neck
dissection, and left-sided neck dissection was performed with extended
supra-omohyoid neck dissection. Because the tongue tumor was located
anterior to the sublingual surface, partial tongue resection did not
create oral cavity and neck traffic. Tracheostomy was performed owing to
concerns about postoperative airway narrowing because of the bilateral
cervical dissection.
Histopathologically, the tongue cancer was radically resected, and one
metastatic lymph node was found at left level IB and three at left level
III, none of which showed extranodal extension (Figure 7). Additionally,
the right cervical lymph node, which had been in remission after
treatment for Hodgkinʼs lymphoma, showed no normal lymph node structure,
with internal vitreous degeneration and no evidence of squamous cell
carcinoma metastasis or Hodgkinʼs lymphoma (Figure 8). Postoperative
radiation therapy with cisplatin chemotherapy was proposed owing to the
multiple cervical lymph node metastases of tongue cancer; however, in
accordance with the patientʼs strong desire, a follow-up plan was
chosen.
4. Outcome and follow-up
Three months after treatment for tongue cancer and 1 year and 4 months
after treatment for Hodgkinʼs lymphoma, a solitary enlarged lymph node
was found at right level V. Lymphadenectomy was performed, and the
diagnosis was a relapse of Hodgkinʼs lymphoma (Figure 9). Chemotherapy
was proposed by the hematologist; however, follow-up was again chosen,
in accordance with the patientʼs strong desire. Seven months after the
tongue cancer treatment, there was no evidence of recurrence or
metastasis of the tongue cancer or recurrence of new Hodgkinʼs-affected
lymph nodes, and the patient is scheduled for further follow-up.
5. Discussion
The lymphatic flow in the tongue involves collecting lymphatic vessels
in the lingual apex, lateral border of the tongue, central tongue, and
posterior tongue. The lymphatic vessels in the lingual apex penetrate
the hyoid muscle to the submandibular lymph node; those in the lateral
border of the tongue penetrate the hyoid muscle to the submandibular
lymph node; and those in the central tongue and posterior tongue reach
the internal deep neck lymph nodes through the surface and back of the
tongue hyoid muscle.2 Each lymphatic vessel also has a
left-right crossing and a pathway to the contralateral lymphatic
flow.3 Haagensen et al. also noted the presence of
capillary lymphatic intersections on the surface of the lingual apex
and, in the deep part of the lingual apex, lymphatic flow passing under
the muscle and crossing to the lymph nodes of the contralateral middle
internal jugular vein.4 Previous reports suggest that
tongue cancer often shows contralateral metastasis;5,6however, all previous studies reported metastatic lymph nodes on the
affected side as well,7 and there are no reports, to
our knowledge, of metastasis only on the contralateral side.
The tongue cancer in this case was located at the apex of the tongue
with a DOI of 13.9 mm. In the cervical lymph nodes, there was metastasis
only on the contralateral side and none on the affected side. Because
the tongue cancer was located at the apex of the tongue, and the DOI was
deep, it is quite possible that the lymphatic flow pathways could have
trafficked to the neck bilaterally, either superficially or deeply.
Histopathologically, the cervical lymph node on the affected side in our
case showed no normal lymph node structure. The interior showed vitreous
degeneration, which suggested that lymphatic flow may have been blocked,
and thus, no lymph node metastasis was seen. It is likely that previous
chemotherapy for Hodgkinʼs lymphoma, which involved a primary lesion in
the right cervical lymph node, caused degeneration of the lesion and
blocked normal lymph flow. Additionally, in this case, we were
incidentally able to perform histopathology after remission of Hodgkinʼs
lymphoma. These data may be valuable because there have been no previous
reports, to our knowledge, showing pathological findings or evaluation
of foci that have achieved remission status with chemotherapy for
Hodgkinʼs lymphoma. Furthermore, in the follow-up biopsy, there was a
new relapse of Hodgkinʼs lymphoma of the neck, suggesting that lymphatic
flow is unlikely to have been associated with the development of
Hodgkinʼs lymphoma.
In formulating a treatment plan for this case, evaluation of the
cervical lymph nodes was a challenge. This evaluation meant that it was
necessary to determine whether the lesion in the contralateral cervical
lymph node on imaging evaluation was a metastasis of tongue cancer or a
recurrence of Hodgkinʼs lymphoma. There have been reports of cervical
lymph node metastases from laryngeal cancer treated with cervical
dissection, which were not metastatic lymph nodes but Hodgkinʼs
lymphoma.8 However, to the best of our knowledge,
there are no reports of cervical lymph node lesions for which it was
difficult to evaluate whether the lesions were recurrent Hodgkinʼs
lymphoma or metastases from tongue cancer, as in our case. Therefore, we
considered the following treatment plan: The T classification of the
tongue cancer in this case was cT3 because the DOI was > 10
mm, and the plan was to perform prophylactic right-sided neck
dissection. After a diagnosis is confirmed by biopsy of the
contralateral cervical lymph node, there is a method of treatment for
tongue cancer. However, this method delays the start of tongue cancer
treatment by several weeks as the patient waits for biopsy results, and
the invasive procedure is performed twice, increasing the patientʼs
psychological burden. Therefore, in this case, a contralateral lymph
node biopsy was diagnosed quickly intraoperatively, and surgery for
tongue cancer was performed at the same time. If the tongue cancer had
been diagnosed as cT2, the same approach would have been followed, with
intraoperative rapid diagnosis of the contralateral lymph node.
The American Cancer Society guidelines state that patients treated for
Hodgkinʼs lymphoma are at increased risk of developing various secondary
cancers, and cancers of the “lip and oral cavity” are
mentioned.9 In this case, the patient had undergone
chemotherapy for Hodgkinʼs lymphoma prior to the development of the
tongue cancer, and the possibility of a second cancer was considered.
With the availability of recent remarkable developments in chemotherapy,
we should be aware of the development of secondary cancers in the oral
cavity, which may be treatable with newer chemotherapy regimens. The
evaluation of cervical lymph nodes in tongue cancer after treatment for
Hodgkinʼs lymphoma is important. In cases in which the main lesion is in
the cervical lymph nodes, as in this case, lymphatic flow may be
altered, and caution is needed in interpreting the imaging evaluation
and planning a treatment strategy.
Acknowledgments
We thank Jane Charbonneau, DVM, from Edanz (https://jp.edanz.com/ac) for
editing a draft of this manuscript.
Conflicts of interests
The authors declare that they have no conflicts of interests.
Author contributions
YO contributed to study concept and design and wrote the manuscript. KK,
HY, KK, DS, SO, KT, JM, and TK contributed to data acquisition. We also
confirm that all authors have read and approved the final version of
this manuscript.
Ethical approval
The Iwate Medical University Institutional Review Board exempted ethics
approval for case reports.
Funding
This case report was funded by JSPS KAKENHI (Grant Number JP20K10251).
Consent
Full consent for participation and publication was provided by the
patient.
Data availability statement
The date that support the findings of this study are available from the
corresponding author upon reasonable request.
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Figure Legends
Figure 1: Findings at the time of Hodgkin’s lymphoma
Fluorodeoxyglucose positron emission tomography reveale many lymph nodes
with abnormal accumulation and with a maximum standardized uptake value
of 15.7 at the right cervical lymph node (A). Histopathological
findings. Hematoxylin-eosin stain of the lymph node (A), Positive
results were observed in the immunohistochemical study for CD30 (C) and
PAX5 (D).
Figure 2: Findings of the tongue tumor
A tumor was observed on the right tongue. The tumor was 28 mm in long
diameter, with induration around the tumor and in the deep tissues.
Figure 3: Findings of the Panoramic X-ray image
The proximal roots of 44‒46 were intact, and a dental implant was
present in the equivalent area of 47.
Figure 4: Findings of the Computed Tomography
The tumor was 24 × 19.3 × 14.2-mm from the right lingual apex to the
edge of the tongue (A). Mildly swollen lymph node was observed in the
right Level III (B). Hypoabsorption of contrast was seen in the left
level IB (C) and III (D) lymph nodes.
Figure 5: Findings of the Magnetic resonance imaging
The tumor was 23.4 × 19.6-mm, large tumor with a depth of invasion (DOI)
of 13.9 mm from the right lingual apex to the edge of the tongue (A).
Mildly swollen lymph node was observed in the right Level III (B).
Hypo-absorption of contrast was seen in the left level IB (C) and III
(D) lymph nodes.
Figure 6: Findings of the Fluorodeoxyglucose Positron Emission
Tomography
The tumor was seen with abnormal accumulation and with a maximum
standardized uptake value of 14.46 at the right lingual border.
Additionally, enlarged lymph nodes were seen at left levels IB (C) and
III (D), with abnormal accumulation and maximum standardized uptake
values of 4.10 and 9.00, respectively. There was no accumulation in the
right Level III lymph node (B).
Figure 7: Histopathological Findings of tongue cancer and cervical lymph
nodes at the left Leve IB and Level III
The tongue squamous cell carcinoma was radically resected (A).
Metastatic lymph node of squamous cell carcinoma was found at left level
IB (B) and three at left level III (C), none of which showed extranodal
extension.
Figure 8: Histopathological Findings of cervical lymph nodes at the
right Level III
The right cervical lymph node showed no normal lymph node structure,
with internal vitreous degeneration and no evidence of squamous cell
carcinoma metastasis or Hodgkinʼs lymphoma. (A) Macro image, (B)
Enlarged image
Figure 9: Findings at the relapse of Hodgkin’s lymphoma
The Computed Tomography reveale a lymph node at the right Level V (A).
Histopathological findings. Hematoxylin-eosin stain of the lymph node
(B), Positive results were observed in the immunohistochemical study for
CD15 (C) and CD30 (D).