Diagnosis of a rare case of malignant metastatic tumor on fine-needle aspiration of cervical lymph nodes and subcutaneous nodules
How to cite this article: Inuganti RV. Diagnosis of a rare case of malignant metastatic tumor on fine-needle aspiration of cervical lymph nodes and subcutaneous nodules. CytoJournal 2021;18:1.
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A 69-year-old female patient presented with multiple bilateral swellings in the neck region of 20 days duration. The right posterior triangle lymph node was large necrotic and fixed to the skin. The left posterior triangle lymph node was small necrotic and fixed to the skin. There was a history of on and off fever. FNA was done from both lymph nodes.
What is your interpretation?
Metastatic malignant melanoma
Metastatic melanotic medullary carcinoma thyroid
Metastatic malignant paraganglioma
Metastatic pigmented malignant schwannoma.
The correct cytopathology interpretation is:
b. Metastatic melanotic medullary carcinoma thyroid.
The right and left cervical lymph node smears showed rich cell yield consisting of round to oval cells with moderate amount of eosinophilic cytoplasm, hyperchromatic round nuclei with anisonucleosis. Neither nuclear inclusions nor nuclear grooving was seen. Some cells showed eccentric plasmacytoid nuclei and were mostly arranged discretely and in loose sheets with very occasional well-defined follicle formation. Few cells exhibited brown pigment in their cytoplasm. Considerable numbers of binucleated and trinucleated tumor giant cells were seen. No lymph nodal cellular elements were seen in the smear. The tumor cells exhibited high mitotic activity [Figure 1a and b].
Clinical history revealed no skin lesion past or present, whereas an ultrasound examination of the neck showed few well defined hypoechoic lesions with vascularity in both lobes of thyroid along with the right and left cervical lymphadenopathy. The serum calcium levels were elevated and thyroid profile was normal.
Subsequently, a biopsy of the left cervical lymph node was done.
Gross examination: We received two gray-white tissue fragments of sizes 2.5 × 1.5 × 1 cm and 1.5 × 1 × 1 cm.
Sections showed near total replacement of lymph node by sheets of pleomorphic epithelioid cells and a few tumor giant cells. Some tumor cells were arranged in vague follicular pattern and a few cells showed intracytoplasmic brown pigment [Figure 1c]. The report signed out was that the histopathological picture is suggestive of secondary deposits from a melanotic medullary carcinoma of the thyroid. Immunohistochemical markers were positive for chromogranin [Figure 1d] and HMB 45, with a negative result for TTF1.
In view of the cytological diagnosis, the patient was further evaluated by ultrasound examination of the neck which showed few well defined hypoechoic lesions with vascularity in both lobes of thyroid along with the right and left cervical lymphadenopathy. The serum calcium levels were elevated and thyroid profile was normal.
The patient refused further treatment and was discharged. Twenty days later, she came back with painless subcutaneous masses in the inframammary and scalp region, which she had noted for 3 days.
On examination, three swellings were noted in the subcutaneous plane in the right hypochondrium (1 × 1 × 1 cm), left inframammary area (1.5 × 1.5 cm), and frontal area of the scalp (0.5 × 0.5 cm) which were firm in consistency, non-tender, immobile, with skin over swelling being normal. Cytology of these three masses also revealed a similar picture as before and reported as metastatic deposits from medullary carcinoma of thyroid, melanotic variant and was confirmed by histopathology. FNA of the thyroid was also done and showed a similar cytological picture. The patient refused further treatment and left against medical advice.
ADDITIONAL QUIZ QUESTIONS
Q1: What is the cell of origin of medullary carcinoma? (a) Thyroid follicular cells (b) chief cells of parathyroid (c) C cells of ultimobranchial body (d) oxyphil cells of parathyroid.
Q2: Which immunohistochemical marker is not expressed in medullary carcinoma (a) calcitonin (b) CEA (c) PAX 8 (d) thyroglobulin.
Q3: All of the following are variants of medullary carcinoma except (a) spindle cell variant (b) small cell variant (c) giant cell variant (d) large cell variant.
ANSWERS TO THE ADDITIONAL QUESTIONS
Q1: c; Q2: d; and Q3: d. Q1: (c) Medullary carcinoma of the thyroid constitutes 5–10% of all thyroid malignancies and the tumor derives from para follicular C cells of neural crest origin. Q2: (d) Medullary carcinoma of the thyroid is positive for IHC markers calcitonin, CEA, and PAX8, whereas it is negative for thyroglobulin and estrogen receptor. Q3: (d) Medullary carcinoma of the thyroid has many variants such as amphicrine variant, angiosarcoma-like, clear cell, encapsulated, follicular, giant cell, melanotic, oncocytic, papillary, paraganglioma-like, pseudopapillary, small cell, spindle cell, and squamous. There is no large cell variant described.
Medullary carcinoma of the thyroid constitutes 5–10% of all thyroid malignancies and the tumor derives from parafollicular C cells of neural crest origin. The tumor presents variable morphological features and follicular and papillary variants in addition to small cell, giant cell, clear cell, oncocytic, squamous, and melanocytic variants. Medullary carcinoma with melanocytic differentiation has first been reported by Marcus et al. and is a rare variant. Medullary carcinoma is important because detection of the precursor lesion (C-cell hyperplasia) and the genetic mutation in the RET gene in certain cases can help to prevent this tumor.
Fine-needle aspiration cytology (FNAC) is an important diagnostic procedure for any palpable swelling and is especially useful in neck masses. Metastatic deposits in lymph nodes are diagnosed with ease in FNAC including typing with a possible reference to the primary site. Frequently, metastatic deposits in lymph nodes are discovered initially with a search for the primary as in our case.
The differential diagnosis in the present case was between a malignant melanoma which can mimic any tumor and a melanotic variant of medullary carcinoma of thyroid. The former diagnosis was ruled out as there was no history of a pigmented lesion past or present. Immunohistochemistry also aided in the diagnosis, as the tumor was positive both for chromogranin and HMB 45.
Histological and immunohistochemical studies confirmed the cytological diagnosis. A similar case was reported by De Lima et al. in a 20-year-old male patient, in whom they noticed binucleated cells and multinucleated cells in cytology smears, with abundant, finely granular cytoplasm, some containing a brown pigment resembling melanin.
Melanocytic differentiation in medullary carcinoma of thyroid is very rare. The prognostic and therapeutic significance of this variant of medullary thyroid carcinoma (MTC) is not exactly known, but this variant appears to be more aggressive. Qin and Ji reported a similar case and quoted that it is necessary to report more cases for exact biological behavior and prognosis.
Hirokawa et al. reported a case of melanin producing medullary carcinoma of thyroid that showed pleomorphic, atypical cells which expressed markers both for MTC and melanoma. The tumor cells were morphologically similar to melanoma. In the present case, the tumor cells were morphologically similar to a medullary carcinoma of thyroid rather than a melanoma. FNAC of the lymph nodes, subcutaneous lesions, and thyroid was similar and histopathology of the lymph nodes and subcutaneous lesions confirmed the diagnosis with the aid of immunohistochemical markers. The patient refused further surgical intervention and was discharged from the hospital.
COMPETING INTEREST STATEMENT BY ALL AUTHORS
The authors declare that they have no competing interest.
AUTHORSHIP STATEMENT BY ALL AUTHORS
Each author has participated sufficiently in the work and takes public responsibility for the appropriate portions of the content of this article. SK carried out substantial contributions to conception and design, acquisition of data, and drafting the article. AA carried out substantial contributions to conception and design, acquisition of data, drafting the article, and revising it critically for important intellectual content.
ETHICS STATEMENT BY ALL AUTHORS
As this is case report without identifiers, our institution does not require approval from the Institutional Review Board (or its equivalent).
LIST OF ABBREVIATIONS (In alphabetic order)
FNA – Fine-needle aspiration
FNAC – Fine-needle aspiration cytology
MTC – Medullary thyroid carcinoma.
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