Metastatic squamous cell carcinoma thyroid from functionally cured cancer cervix.

The authors report a very unusual occurrence of a metastatic squamous carcinoma to thyroid gland from a treated squamous cell carcinoma cervix 12 years before with no recurrence at the primary site. The case also has an additional complexity of rapid progression of the metastatic thyroid carcinoma to wide spread dissemination to lungs and bones while on concurrent chemo radio therapy confirming the aggressiveness of the entity.

INTRODUCTION

Metastases to the thyroid gland have been described as early as the 1930s.[1] Only 1% of all clinically detectable thyroid cancers are of metastatic origin.[2] Squamous cell carcinoma involving thyroid gland is an extremely rare condition. The origin of the metastatic thyroid lesions commonly arises predominantly from kidney, breast, lung and gastrointestinal system. The interval between the onset of primary and the metastatic insult usually is less than 2 years with variations in duration dependent upon the histopathological aggression of the primary.[3] Metastatic deposits to thyroid from squamous carcinoma cervix is not widely reported. We present the case of a patient with cervical carcinoma who developed thyroid metastases 12 years after curative treatment of the primary tumor. The long interval between the primary and metastasis throws up the possibility of a second primary, but primary squamous carcinoma is a much rarer entity than squamous metastasis.

CASE REPORT

A 68-year-old female patient presented with swelling in the left side of the neck of 6 weeks duration progressively increasing in size and not associated with any pain, difficulty in swallowing or alteration of speech. The swelling was located in the lateral aspect of neck, lobulated and appeared lymph nodal in origin. There was also an associated nodular swelling of the left lobe thyroid. Ultrasonography of neck revealed multiple necrotic cervical lymph nodes on the left side and multiple hypo echoic nodules in the left lobe associated with thyroid enlargement. Positron emission tomography/computed tomography (PET/CT) revealed hyper metabolic multiple level left cervical lymph nodes with necrosis and hypermetabolic large hypo dense nodule with specks of calcification in the left lobe thyroid, few small hypo dense nodules were also seen in the right lobe as well [Figure 1]. Fine needle aspiration cytology from the cervical node and thyroid revealed keratinizing squamous cell carcinoma. Detailed clinical history of the patient revealed previous histopathological evidence of squamous cell carcinoma cervix that had occurred 12 years ago and treated with hysterectomy followed by post-operative radiation to pelvis. Patient underwent total thyroidectomy and radical neck dissection on the left side of the neck. Histopathology revealed thyroid follicles with adjacent tumor tissue composed of polygonal cells with vesicular pleomorphic nuclei, prominent nucleoli and a moderate amount of eosinophilic cytoplasm arranged in sheets with focal keratin pearl formation suggestive of squamous carcinma amidst thyroid follicles [Figure 2]. The thyroid specimen was subjected to real time polymerase chain reaction study for any presence of high risk human papilloma virus signature, which is not detectable patient was given post-operative radiotherapy to neck along with concurrent chemotherapy with weekly cisplatin. Interim PET/CT after 6 weeks surprisingly revealed extensive disease with the multiple metabolically active lung, liver and bone metastasis [Figure 3]. Patient was restaged with progression of disease and management changed from curative to palliative intent.

Figure 1

Positron emission tomography/computed tomography showing one of the hyper metabolic enlarged left cervical lymph node with central necrosis and hyper metabolic large nodule in the left lobe thyroid

Figure 2

Low and high power views of thyroid specimen showing thyroid follicles with adjacent squamous cell carcinoma

Figure 3

Interim positron emission tomography/computed tomography showing multiple metabolically active lung liver and bone metastasis

DISCUSSION

The most cervical cancers are squamous cell carcinomas. The cure rate is 100% in early stage disease while it is 5% in the late stage.[45] Disease free interval after treatment depends upon the initial stage of the tumor and the adequacy of initial treatment. Recurrent disease is associated with poor prognosis and the tumor tends to relapse in pelvis, retroperitonium and distant sites. Until 70% of patients with cervical cancer who present with nodal metastases and/or locally advanced disease will relapse. Cervical cancer gives distant metastases through the lymphatic spread, from the satellite nodes to the paraaortic and supraclavicular nodes. The route of the hematogenous spread is presumed to occur via the blood stream to the caval venous system through the lung parenchyma and systematic circulation. In patients who develop distant metastases, the most frequently observed metastatic sites are the lung (21%), paraaortic lymph nodes (11%), abdominal cavity (8%) and supraclavicular lymph nodes (7%), bone metastases (16%) and metastatic carcinoma of the thyroid gland from cancer of the cervix being very rare.[6] Utility of fluorodeoxyglucose (FDG)/PET in staging of cervical carcinoma has been studied and shows high accumulation of FDG in both primary and metastatic lesion attributed to over expression of glucose transporter-1 in the tumor and does not correlate with the initial grade of histological differentiation and staging.[7] Metastatic carcinoma to thyroid gland forms only a meager 1% of all the thyroid cancers.[2] Post mortem revelation of secondary tumors in thyroid gland might be up to ten times more common than primary thyroid cancer.[3] Some autopsy studies describe thyroid metastatic lesions in as many as 24% of patients with disseminated disease, although in most cases, there is no evidence of clinical manifestations from thyroid infiltration.[4] Metastatic spread from squamous cell carcinomas to thyroid is uncommon, as squamous cell carcinomas predominantly recur locally and spread to loco regional lymph nodes. The most common primary sites of origin of the metastatic thyroid lesions are cancers of the kidney, breast, lung and gastrointestinal system and melanoma. The mean interval from the diagnosis of the primary tumor to the development of the thyroid metastasis is 14 months, the range varying according to the histological type.[58] Carcinoma cervix is not widely known to metastasize to thyroid, as the common behavior is one of local recurrence and retroperitoneal lymph node spread.[9]

Our case has a history of treated carcinoma cervix 12 years back with metastasis to unusual site of thyroid gland that too 7 years post-functional cure period of 5 years, with primary cervical cancer showing no local recurrence or regional spread. The other possibility of the thyroid squamous cell carcinoma is a second primary in the thyroid or multiple malignancies which are defined as either synchronous or metachronous. Synchronous tumors are defined as tumors that are diagnosed within 6 months of each other and metachronous tumors are tumors that are diagnosed with an interval of more than 6 months of the primary tumor at a second site. Both synchronous or metachronous, tumors is not an unusual feature in the head and neck squamous cell carcinoma with incidence of 20% of patients developing a secondary malignancy, but such a behavior is not known to occur in squamous carcinoma of the cervix.[10] Primary squamous cell cancer thyroid is an even rarer entity than metastatic squamous cell carcinoma and is presumably the result of squamous elements contained in thyroglossal cyst and carcinoma arising from these cells in a persistent remnant of the thyroglossal tract, the other possibility is squamous metaplastic transformation of papillary or follicular elements of the thyroid follicle. The incriminating element for such a transformation is being attributed to Hashimoto's thyroiditis. All these are only hypothetical and have no proven implicating evidence.

CONCLUSION

The case illustrates rare multiple phenomena of metastatic thyroid carcinoma from a functionally cured squamous cell carcinoma of cervix 12 years after the onset of primary cervical cancer and rapid progression of the disease while on chemotherapy signifying the intense invasive potential of the squamous carcinoma metastasis.