|Year : 2012 | Volume
| Issue : 2 | Page : 60-63
Spindle cell variant of medullary carcinoma of thyroid with nodal metastasis: Cytodiagnosis and diagnostic dilemma
Santosh Kumar Mondal1, Dipanwita Roy Nag1, Ranjana Bandyopadhyay2
1 Department of Pathology, Medical College, Kolkata, India
2 Department of Pathology, Malda Medical College, West Bengal, India
|Date of Web Publication||12-May-2012|
Santosh Kumar Mondal
Teenkanya Complex, Flat 1B, Block B, 204 R N Guha Road, Dumdum, Kolkata- 700 028, West Bengal
Source of Support: None, Conflict of Interest: None
A 45-year-old female presented with a thyroid nodule on right lobe since 2 years and an enlarged cervical lymph node for past 6 months. Fine needle aspirations were done from the thyroid nodule. Fine needle aspiration cytology from thyroid swelling revealed discretely arranged elongated spindle-shaped cells with scant cytoplasm. Clumps of glassy pink amyloid-like material were noted in the background on air-dried smears. A provisional cytodiagnosis of spindle cell variant of medullary carcinoma of thyroid (MCT) was made based on cytomorphology. But diagnostic dilemma appeared as spindle cell tumor might mimic fibroblasts from supporting stroma, melanoma, or even anaplastic carcinoma. Distinction of amyloid from hyaline collagen or basement membrane material was also difficult on cytologic smears. Subsequently, serum calcitonin measurement and histopathological examination confirmed the case to be spindle cell variant of MCT with nodal metastasis.
Keywords: Fine needle aspiration cytology, medullary carcinoma, spindle cell, thyroid
|How to cite this article:|
Mondal SK, Nag DR, Bandyopadhyay R. Spindle cell variant of medullary carcinoma of thyroid with nodal metastasis: Cytodiagnosis and diagnostic dilemma. Thyroid Res Pract 2012;9:60-3
|How to cite this URL:|
Mondal SK, Nag DR, Bandyopadhyay R. Spindle cell variant of medullary carcinoma of thyroid with nodal metastasis: Cytodiagnosis and diagnostic dilemma. Thyroid Res Pract [serial online] 2012 [cited 2020 Jul 6];9:60-3. Available from: http://www.thetrp.net/text.asp?2012/9/2/60/96057
| Introduction|| |
Medullary carcinoma of thyroid (MCT) is a rare neuroendocrine thyroid malignancy. It arises from parafollicular or c-cells. Both sporadic and familial forms occur and majority of cases are sporadic (70%). MCT is usually found in middle-aged persons with a female preponderance and presents with a solitary nodule in most of the cases.
In patients with thyroid nodule, fine needle aspiration cytology of the thyroid gland (FNAC-t) is widely used as an initial and crucial investigation to select those patients who require excision of the lesion for histopathological confirmation.  If FNAC-t diagnose suspicious or malignant thyroid lesion, surgery is indicated.  Pure spindle cell MCT comprises only a small proportion in majority of the series.  Cytodiagnosis of spindle cell variant of MCT is difficult as diagnostic dilemma occurs with other entities.
| Case Report|| |
A 45-year-old lady presented with a thyroid swelling on upper portion of right lobe for the last 2 years and an enlarged cervical lymph node on right side for the last 6 months. Ultrasonography revealed a hypoechoic mass (3 × 2.5 cm). The patient complained of hoarseness of voice, dypsnea, and dysphagia for the last 8 months. Physical examination showed an oval, firm to hard swelling which moved on deglutition. There was no family history of similar thyroid swelling or any other endocrine disorder.
FNAC from thyroid nodule was done using 23G needle. The air-dried smears were stained by May-Grunwald Giemsa (MGG) stain and alcohol-fixed smears were stained by Papanicolaou (Pap) stain. MGG stained smears showed high cellular yield. The tumor cells were spindle shaped and arranged discretely [Figure 1]. The nucleus was centrally located and cytoplasm was less distinct. The cells have hyperchromatic nuclei with indistinct nucleoli. Most of the cells were monomorphic although mild pleomorphism was noted. Red granules in the cytoplasm were absent. Binucleated and multinucleated cells were also not seen. Clumps of amyloid like pink, amorphous and glassy material were seen in the background [Figure 2]. Pap-stained smears showed spindle cells with a speckled nuclear chromatin and clumps of orangeophilic amyloid-like material in the background. Based on cytomorphology (spindle-shaped tumor cells and amyloid material), a provisional cytodiagnosis of spindle cell variant of MCT was made. A histopathologic examination and serum calcitonin measurement were advised for confirmation of the diagnosis.
|Figure 1: Cytologic smear showing high cellular yield and composed of discretely arranged spindle shaped tumor cells. Glassy pink materials (amyloid) were present in the background. (MGG, ×100)|
Click here to view
|Figure 2: High power view of the smear showing discretely arranged tumor cells with little pleomorphism. Clumps of amyloid material are present in the background. (MGG, ×400)|
Click here to view
A total thyroidectomy along with excision of the cervical lymph node was done. Cut section revealed an unencapsulated tumor measuring 3 × 2.5 cm and was confined to the upper portion of right lobe. The cut surface was yellowish white with areas of hemorrhage and necrosis. We sampled the entire tumor into three blocks along with surrounding thyroid parenchyma in other blocks. Microscopic examination revealed spindle -shaped tumor cells in a diffuse pattern. Nucleoli were indistinct and mitotic figures were rare. Amyloid-like material was abundant in the background [Figure 3]. Subsequently, Congo red staining was done which became positive and confirmed the amyloid within the tumor. Serum calcitonin was also very high. Histopathological examination of the cervical lymph node revealed metastatic deposit of the tumor in the subcapsular sinuses. The metastatic deposit was composed of spindle cells similar to the tumor of thyroid.
|Figure 3: Histologic section showing thyroid nodule composed of spindle shaped tumor cells. Nuclear pleomorphism is mild and mitotic count is very low. Abundant amyloid materials were seen in the background. (H and E, ×400)|
Click here to view
Thus, a confirmatory of diagnosis of spindle cell variant of MCT with cervical lymph node metastasis was established.
| Discussion|| |
MCT is the first human malignancy which is associated with a tumor marker, the calcitonin hormone. Measurement of serum calcitonin has diagnostic and prognostic values, following surgical resection of thyroid tumor (MCT).  In the familial type of MCT, identification of the precursor lesion and genetic mutation enables early diagnosis. This tumor is associated with other endocrine disorders such as pheochromocytoma, parathyroid hyperplasia, as part of the multiple endocrine neoplasia syndrome.
Smears from MCT are usually moderately to highly cellular, composed of predominantly dispersed cells although some syncytial aggregates may also be seen. The cells may be plasmacytoid, epithelioid, small cell, spindle cell, or mixed type; epithelioid/plasmacytoid being the commonest cell pattern in majority of the series. In most tumors, some cells show prominent cytoplasmic granularity staining bright red with MGG. These granules are seen best in large or multinucleate cells. , But in our case, no cytoplasmic granule was observed and large or multinucleated cells were absent in the smears. Das et al found cytoplasmic red granules in all of their 12 cases but only 10-20% of cells and less commonly in spindle cells.  The "neuroendocrine" nuclear appearance is seen in tumor cells, namely, granular chromatin, inconspicuous nucleoli, and ill-defined nuclear membrane. A distinct neuroendocrine nuclear appearance could not be confirmed by air-dried/MGG-stained smears and better visualized in pap-stained smears which reveals speckled or "salt and pepper" chromatin.  Occasionally, nuclear cytoplasmic inclusions or nuclear moulding/ grooving similar to those of papillary carcinoma are observed.  Moderate nuclear and cellular pleomorphism are seen in most of the cases.  But in our case although neuroendocrine appearance was present, other nuclear features were absent. The finding of spindle cells along with other type of cells (plasmacytoid, epithelioid, and small cell) is not uncommon on cytologic smears and authors have reservations on use of the terminology on FNAC report as "spindle cell variant." But in our case the smears were predominantly composed of spindle cells and other cells were not seen. So, a provisional diagnosis of spindle cell variant of MCT was made on FNAC and later on confirmed by histologic examination.
Amyloid is identified in 43-81% of cases.  It appears as dense amorphous clumps which stain variable shades of magenta with MGG and greyish orange with pap staining.  Congo red staining and dichroism confirm the amyloid material which otherwise might be confused with colloid or connective tissue and in particular with the stroma of hyalinising trabecular adenoma.  The tendency to dispersal, epithelioid, and spindle cells with plasmacytoid appearance, granular chromatin, and absence of nucleoli are clues to the cytodiagnosis of MCT. 
Pure spindle cell variant of MCT is rare. Spindle cells are usually seen in mixed type of epithelioid and spindle cells. Cytodiagnosis of this tumor is not easy as a number of differential diagnoses may arise. Spindle cells of MCT may resemble fibroblastic tumor, benign or low-grade soft tissue tumors, spindle cell melanoma, or even anaplastic carcinoma. , In nodular or colloid goitre, fibroblasts from supporting stroma or granulation tissue may mimic spindle cells of MCT. Geddie et al found hot nodules in thyroid with like columnar cells, atypical cells, and mitoses. Other two close differentials are hyalinizing trabecular adenoma and nodular fascitis variant of papillary carcinoma. The former case is differentiated by calcitonin negativity and absence of Congo red-positive amyloid material. The classic neuroendocrine/granular chromatin is absent in nodular fascitis variant of papillary carcinoma. On the contrary, ground-glass appearance, nuclear grooves, intranuclear inclusions are seen in nodular fascitis variant of papillary carcinoma but not in spindle cell variant of MCT. Moreover, thyroglobulin is positive in nodular fascitis variant of papillary carcinoma unlike MCT which is calcitonin positive. Neuroendocrine (granular) appearance of nuclear chromatin, cytoplasmic red granules in resolving cytologic criteria for spindle cell variant of MCT, ancillary tests, and histopathologic examination are required for definitive diagnosis. ,
Electron microscopy reveals electron dense neurosecretory granules, varying from 160 to 300 nm, confirming the diagnosis of MCT. Immunocytochemistry for calcitonin has been regarded by some as gold standard for definitive cytodiagnosis although some cases are negative. In a study, it was found that serum calcitonin measurement was superior to FNAC to diagnose MCT (98% vs. 63%), but only 9% of patients have escaped to surgery based on FNAC reports.  In another study of 78 cases of MCT, a definitive cytodiagnosis was made in 54 cases, which in 87.1% was based on cytomorphology alone and in 12.9% was based on ICC for calcitonin. 
An experimental technique has recently been reported in which the tumor cells of MCT fluoresce in vivo.  This technique has an added advantage to determine adequate resection margin during surgery.  Another interesting new technique has been published, which is based on calcitonin measurement in FNAC washout fluid. 
Although correct diagnosis is made by FNAC in majority of cases of MCT, cytodiagnosis of especially rare variant-like pure spindle cell variety of MCT should be confirmed by histopathologic examination and other ancillary tests.
| References|| |
|1.||Giard RW, Hermans J. Use and accuracy of fine-needle aspiration cytology in histologically proven thyroid carcinoma: An audit using a national pathology database. Cancer 2000;90:330-4. |
|2.||Clark OH. Fine-needle aspiration biopsy and management of thyroid tumors. Am J Clin Pathol 1997;108(4 Suppl 1):S22-5. |
|3.||Mehdi G, Maheshwari V, Ansari HA, Sadaf L, Khan MA. FNAC diagnosis of medullary carcinoma of thyroid: A report of three cases with review of literature. J Cytol 2010;27:66-8. |
|4.||Orell SR, Sterrett GF, Whitaker D, Fine needle aspiration cytology. 4 th ed. New Delhi: Elsevier; 2005. p. 125-64. |
|5.||Das A Gupta SK, Banerjee AK, Srinivasan R, Radotra BD, Nijhawan R, et al. Atypical cytologic features of medullary carcinoma of thyroid. A review of 12 cases. Acta Cytol 1992;36:137-41. |
|6.||Green I, Ali SZ, Allen EA, Zakowsky MF. A spectrum of cytomorphologic variations of medullary thyroid carcinoma. Fine needle aspiration findings in 19 cases. Cancer 1997;81:40-4. |
|7.||Bugalho MJ, Santos JR, Sobrinho L. Preoperative diagnosis of medullary thyroid carcinoma: Fine needle aspiration cytology as compared with serum calcitonin measurement. J Surg Oncol 2005;91:56-60. |
|8.||Kaushal S, Iyer VK, Mathur SR, Ray R. Fine needle aspiration cytology of medullary carcinoma of thyroid with a focus on rare variants: A review of 78 cases. Cytopathology 2011;22:95-105. |
|9.||Johnson TE, Luiken GA, Quigley MM, Xu M, Hoffman RM. In vivo fluorescence of medullary carcinoma of the thyroid: A technology with potential to improve visualisation of malignant tissue at surgical resection. Ear Nose Throat J 2008;87:E1. |
|10.||Boi F, Maurelli I, Pinna G, Atzeni F, Piga M, Lai ML, et al. Calcitonin measurement in wash-out fluid and metastatic medullary thyroid carcinoma. J Clin Endocrinol Metab 2007;92:2115-8. |
[Figure 1], [Figure 2], [Figure 3]