Myeloid Sarcoma of the Thyroid

Metastases to the thyroid gland are uncommon and may pose a diagnostic dilemma. Leukemic involvement or infiltration of the thyroid gland is rarer still.

A 48-year-old woman presented to Penn State Hershey Medical Center, a tertiary medical center, with acute myeloid leukemia (AML). She underwent an allogeneic stem cell transplant with cells donated by her matched brother. A bone marrow biopsy performed 6 months later showed no active leukemia. She subsequently developed chronic graft versus host disease, from which she recovered.

A year and a half later, the patient developed rapid swelling of the right thyroid gland. Neither respiratory distress nor vocal fold paralysis was noted. A contrast-enhanced computed tomography (CT) scan was performed (figure 1). Fine-needle aspiration biopsy of the right thyroid mass was positive for malignant cells, consistent with myeloid sarcoma (MS) (figure 2).

Figure 1.

Axial CT scan shows gross enlargement of the right thyroid lobe caused by myeloid sarcoma. There is a mass effect on the airway, with shifting of the trachea laterally.

Figure 2.

Hematoxylin and eosin staining of a core biopsy demonstrates thyroid tissue infiltrated by large, atypical blasts with a high nuclear-to-cytoplasmic ratio, delicate chromatin and nucleoli. Apoptotic cells were frequent; entrapped thyroid follicles are seen in the background (original magnification × 60).

Cytology, as well as further core needle biopsy samples, revealed thyroid tissue infiltrated by blast-like cells with a high nuclear-to-cytoplasmic ratio, a fine chromatin pattern, and variable prominent nucleoli. Tumor cells expressed immunohistochemical staining for CD34, CD117, lysozyme, and myeloperoxidase (figure 3). Flow cytometry confirmed the presence of myeloid blasts, which were positive for CD13, CD33, CD34, CD117, HLA-DR, CD56, and CD64; and negative for CD3 and CD19.

Figure 3.

Thyroid core needle biopsy illustrates neoplastic cells staining positive for myeloperoxidase (A) and CD34 (B) (original magnification × 40).

Given the patient's history of AML, these features were consistent with MS of the thyroid. She was treated subsequently with cladribine, cytarabine, and filgrastim with mitoxantrone (CLAG-M) and had a complete response. She was referred to Otolaryngology to discuss the role of thyroidectomy.

Myeloid sarcomas, extramedullary lesions composed of myeloid lineage blasts, typically form tumors that may precede, follow, or even occur in the absence of systemic AML. ¹ Symptoms arise primarily from compression by the tumor and dysfunction of the affected tissues or organ. ²

MS is a rare diagnosis found in less than 1% of patients with AML, and often misdiagnosed as malignant lymphoma. ³ Patients who have undergone allogeneic stem cell transplants are more likely to suffer from isolated myeloid sarcoma at relapse. Identification of phenotypic markers of myeloid disease, such as myeloperoxidase, CD34, and CD117, is necessary to establish the diagnosis. ¹

This case presents an extreme rarity, as only one case of myeloid sarcoma of the thyroid has been reported previously. ⁴ Metastases comprise less than 0.2% of all thyroid malignancies, led by renal cell carcinoma and followed by colorectal and lung carcinoma, breast and skin cancer, respectively. ⁵ In solid organs involved in MS such as the thyroid, the neoplastic cells appear to be cohesive, mimicking metastasis. ⁴ The diagnostic workup includes an ultrasound, followed by fine needle biopsy or core needle biopsy. ⁵

While no prospective studies have directedly assessed the impact in ALM patients, MS is typically considered to portend poor clinical outcomes. ⁴

Sixty-six to 88% of patients with isolated MS will develop AML at a mean of 9 to 11 months after diagnosis, heralding poor prognosis. ⁴ Although optimal treatment is yet to be established, AML-like induction chemotherapy is typically recommended for isolated MS with hopes of delaying progression to overt leukemia. ⁶ Surgery should be considered for nonresponsive disease or compressive symptoms. ²

The patient is alive and free of disease 2 years after her initial diagnosis. However, the likelihood of recurrence of her AML is high.