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Year : 2018  |  Volume : 14  |  Issue : 3  |  Page : 697-700

Surgical resection of solitary distant metastasis from locoregionally controlled advanced hypopharyngeal malignancy: A ray of hope

Department of Radiation Oncology, Amrita Institute of Medical Sciences and Research Centre, Kochi, Kerala, India

Date of Web Publication12-Jun-2018

Correspondence Address:
Dr. Chelakkot G Prameela
Department of Radiation Oncology, Amrita Institute of Medical Sciences, Kochi, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.172124

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 > Abstract 

Head and neck malignancies have always been challenging for the clinician, both with regards to locoregional control and distant metastasis. Aggressive approaches translate to an acceptable locoregional control, but distant failures pose a dilemma. Newer, sophisticated, imaging modalities have helped in early diagnosis of solitary metastasis, and in turn have opened up an array of interventional procedures, which to some extent improve the disease-free survival and quality of life, as was seen in the present case of locoregionally controlled advanced hypopharyngeal malignancy who presented with solitary distant metastasis. Still, diligent care needs to be taken not to aggravate the scenario with these interventions.

Keywords: Drain site metastasis, hepatic metastasis, hypopharyngeal carcinoma

How to cite this article:
Prameela CG, Ravind R, Sruthi K, Nair HM, Dinesh M. Surgical resection of solitary distant metastasis from locoregionally controlled advanced hypopharyngeal malignancy: A ray of hope. J Can Res Ther 2018;14:697-700

How to cite this URL:
Prameela CG, Ravind R, Sruthi K, Nair HM, Dinesh M. Surgical resection of solitary distant metastasis from locoregionally controlled advanced hypopharyngeal malignancy: A ray of hope. J Can Res Ther [serial online] 2018 [cited 2020 May 24];14:697-700. Available from: http://www.cancerjournal.net/text.asp?2018/14/3/697/172124

 > Introduction Top

Intensity-modulated radiation therapy with or without concurrent chemotherapy has been the standard-of-care for head and neck squamous-cell carcinoma (HNSCC). Documented gain in overall survival has ironically not paralleled the gain in locoregional control. This has been attributed to increased incidence of distant metastases.[1]

 > Case Report Top

A 72-year-old lady, a case of SCC, left pyriform fossa, staged T4bN2cM0 (prevertebral space extension) Stage-IVA with appropriate imaging, at presentation, received radical concurrent chemoradiation (7000 cGy, weekly-cisplatin-40 mg/m 2). She was on regular follow-up. Positron emission tomography (PET) scan done 11 months post-treatment showed fluorodeoxyglucose-avid hypodense-lesion measuring 4 (Tr) × 3.2 (AP) × 2.8 (CC) cm involving segment IVA of liver [Figure 1]. Locoregional area being negative, the possibility of different pathology was considered. Gastroenterology opinion was sought, who opted for laparoscopic left hepatectomy. Final histopathology was metastatic SCC (6.5 cm × 3.8 cm × 3.6 cm). Vascular emboli and necrosis were present. Isolated tumor lobules and vascular emboli were seen involving resection margin [Figure 2].
Figure 1: Computed tomography scan showing solitary hepatic lesion 11 months postinitial treatment

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Figure 2: Microscopic picture showing metastatic neoplasm in the liver

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Chemotherapy was deferred in view of the poor general condition. She was kept on follow-up with repeated ultrasonography (USG) evaluations. Nine months postsurgery, she presented with vague abdominal discomfort, and a subcutaneous nodule at drain site. Computed tomography (CT) abdomen showed multiple well-defined minimally enhancing lesions, involving segment VIII, V, and VI. A PET-CT scan done elsewhere showed multiple metastases in lung, liver, postoperative drain site, perigastric node, and serosal deposit over pylorus of stomach [Figure 3]. The PET scan was negative for any loco-regional disease.
Figure 3: Computed tomography scan showing multiple hepatic metastases and subcutaneous nodule at drain site

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Fine needle aspiration from right hypochondriac subcutaneous nodule was consistent with metastatic squamous cell carcinoma [Figure 4]. She was started on metronomic oral Methotrexate, but progressed and succumbed to the disease 112 days after diagnosis of disseminated disease.
Figure 4: Microscopic picture showing metastasis in the drain site nodule

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In spite of meticulous, aggressive primary treatment in a case of SCC of pyriform fossa, solitary distant metastasis was noted in liver within 11 months of completing treatment. Laparoscopic intervention offered a disease-free interval of 9 months though followed by disseminated disease and drain site metastasis, and the patient survived only for a very short period after that.

 > Discussion Top

The incidence of distant metastases in HNSCC accounts for 7–23%,[2] and liver metastasis 4–34%. Reported rate of distant metastases in Stage IV disease is 20% while in N2 nodal status is 9.2%.[2] Distant metastases are high in laryngeal and hypopharyngeal cancers due to advanced stage at presentation, and earlier lymph nodal involvement, facilitated by rich bilateral lympho-vascular ramifications. Spector et al. quoted 17.2% incidence of late distant metastasis from pyriform sinus.[3] Once distant metastases develop the possibility of cure becomes remote, and survival becomes dismal. Aggressive treatments even when instituted early for metastases fail to reap impressive goals.

The meta-analysis of chemotherapy in head and neck cancer (MACH-NC meta-analysis) showed that benefit of radical concurrent chemoradiotherapy was not as impressive in patients aged >70.[4] However, advanced age in index patient did not adversely affect concurrent chemoradiation, and good locoregional control was achieved. Regular follow-up and timely imaging (USG/CT/PET) detects failures early, and aggressive salvage options are feasible.

Newer avenues in the management of hepatic metastases, especially solitary ones opened with the advent of better chemotherapeutic and targeted agents. While hepatic metastases called for systemic chemotherapy earlier, recent trends favor hepatic resection, ablation, and laparoscopic interventions.[5] Benefits of surgical interventions have been documented for colorectal metastases and neuroendocrine primaries. Among noncolorectal, nonneuroendocrine primaries, evidences are scanty and of the few available, favor genitourinary, breast, and sarcomas.[5] Literature search failed to yield evidence for same in HNSCC. Yet, laparoscopic hepatectomy in index case resulted in the disease-free interval of 9 months. Stereotactic body radiotherapy would have been a favorable option in an optimal setting.

Laparoscopic port-site metastasis was first published in 1978 by Döbrönte. Since then there have been multitudes of publications on port-site recurrences, mostly from disseminated intra-abdominal metastases. Laparoscopic port-site metastasis rate of 0.79% from gastrointestinal malignancies and 0.09–0.73% in urological malignancies have been quoted which was equivalent (0.89%) to open procedures.[6],[7] Cutaneous implantation of HNSCC at percutaneous endoscopic gastrostomy site has been reported from as early as 1989.[8] We have had two instances of surgical site implantation in HNSCC; one at the site of a feeding tube placed in the stomach, and another at the drain site of a pectoralis flap.

Various theories have been suggested for port-site metastasis. Biology of the tumor, host factors such as stress, immune response, and inflammatory changes, and factors relating to treatment procedures, have all been implicated. Tissue manipulation and tumor seeding of pneumoperitoneum were earlier implicated as prime causes though recent papers have questioned its authenticity, as the number of cells required for tumor implant is suggested to be extremely high.[7]

In 1978, DerHagopian put forward the concept of oncotaxis, which suggests attraction and transcapillary migration of cancer cells to tissue spaces, and commented that both internal and external causes of inflammation could be potential sites for tumor recurrence. Animal models have a peak of heparin-binding epidermal growth factor, a member of epidermal growth factor receptor family, two days post hepatectomy.[9] Similarly, radiofrequency ablation was also associated with elevated matrix metalloproteinases MMP2 and MMP9 expression. These observations facilitate an environment conducive for tumor growth.[9] Other molecular mediators implicated are tumor necrosis factor, cyclooxygenase-2, vascular endothelial growth factor A, and so on. Granulation tissue acting as a potential niche for tumor implant has been suggested by Potochny in cutaneous metastasis in relation to percutaneous endoscopic gastrostomy.

Emerging concepts of tumor microenvironment allude to dense interactions between tumor cells, surrounding stroma, niche-defining cells, and vasculature enabling tumor progression, assisted by modulation of host inflammatory response by myriad of soluble mediators, both tumorigenic and anti-tumorigenic.[10] Possible mode of spread still remains controversial, and lymphatic, hematogenous, and direct implantation have all been implicated. A combination of factors could have helped dissemination in the index case, like granulation tissue at wound site acting as the niche, direct dissemination in view of vascular emboli in resected margin, and metastatic picture indicating a contiguous spread. Solitary cutaneous, port, or drain site metastasis rarely occurs. It usually is a manifestation of disseminated disease, suggesting aggressive tumor biology augmented by immunosuppression and hematogenous spread.[7] This is further corroborated by Pitman's observation that median survival after cutaneous metastases in HNSCC is 3 months (1–16 months).

 > Conclusion Top

The high metastatic potential of hypopharyngeal malignancies is well-documented, and aggressive treatment in such a setting calls for judicious planning. A wide variety of options is available presently for solitary metastasis in HNSCC with negative primary and regional sites. The possible hazard of tumor seeding and dissemination needs to be critically weighed against benefits of surgical and ablative procedures. A disseminated metastasis, in any setting, narrows down treatment options to palliative best supportive care with emphasis on quality of life.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

Yao M, Lu M, Savvides PS, Rezaee R, Zender CA, Lavertu P, et al. Distant metastases in head-and-neck squamous cell carcinoma treated with intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 2012;83:684-9.  Back to cited text no. 1
Dwivedi RC, Kazi R, Agrawal N, Chisholm E, St Rose S, Elmiyeh B, et al. Comprehensive review of small bowel metastasis from head and neck squamous cell carcinoma. Oral Oncol 2010;46:330-5.  Back to cited text no. 2
Spector JG, Sessions DG, Haughey BH, Chao KS, Simpson J, El Mofty S, et al. Delayed regional metastases, distant metastases, and second primary malignancies in squamous cell carcinomas of the larynx and hypopharynx. Laryngoscope 2001;111:1079-87.  Back to cited text no. 3
Pignon JP, le Maître A, Maillard E, Bourhis J; MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients. Radiother Oncol 2009;92:4-14.  Back to cited text no. 4
Arciero CA, Sigurdson ER. Diagnosis and treatment of metastatic disease to the liver. Semin Oncol 2008;35:147-59.  Back to cited text no. 5
Shoup M, Brennan MF, Karpeh MS, Gillern SM, McMahon RL, Conlon KC. Port site metastasis after diagnostic laparoscopy for upper gastrointestinal tract malignancies: An uncommon entity. Ann Surg Oncol 2002;9:632-6.  Back to cited text no. 6
Chaturvedi S, Bansal V, Kapoor R, Mandhani A. Is port site metastasis a result of systemic involvement? Indian J Urol 2012;28:169-73.  Back to cited text no. 7
  [Full text]  
Preyer S, Thul P. Gastric metastasis of squamous cell carcinoma of the head and neck after percutaneous endoscopic gastrostomy – Report of a case. Endoscopy 1989;21:295.  Back to cited text no. 8
Lejeune FJ. Is surgical trauma prometastatic? Anticancer Res 2012;32:947-51.  Back to cited text no. 9
Elinav E, Nowarski R, Thaiss CA, Hu B, Jin C, Flavell RA. Inflammation-induced cancer: Crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer 2013;13:759-71.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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