Rapid on-site evaluation of a solitary lung nodule in a patient with remote history of hysterectomy: Cytologic findings and diagnostic challenges

BRIEF REVIEW OF THE TOPIC

Endometrial stromal tumors are rare tumors that arise from the endometrial stroma. Low-grade ESS typically occurs in perimenopausal women and has a very indolent course with excellent prognosis.^[3] Distant metastasis can develop many decades after the initial diagnosis.^[3] Pulmonary metastasis from low-grade ESS usually manifests as multiple nodules.^[4-6] Very rarely, however, it can present as a solitary lesion, which can pose significant diagnostic dilemma. Due to its rarity and bland appearance, low-grade ESS has been mistaken for benign lesions or inflammatory processes.^[4,6-9] The diagnostic dilemma is even more challenging in cytology specimen and small biopsies.^[5]

The cytologic features of metastatic low-grade ESS have rarely been described in the literature since it is rarely subjected to fine-needle aspiration.^[4,8-10] In the lung, it has been mistaken for carcinoid tumor, hamartoma, and endometriosis.^[4,5,9] A predominance of bland spindle cells can also be mistaken for leiomyoma and other benign spindle cell neoplasms.^[5,7,8]

The diagnostic challenges of low-grade ESS in cytology have been emphasized by others, and in most case reports of metastatic low-grade ESS, a definite diagnosis was achieved only after performing molecular studies. Zaharopoulos et al.^[10] first described a case of ESS that metastasized to the lung. The fine-needle aspiration biopsy of the lung lesion revealed small cells with scant cytoplasm and low mitosis. An ultrastructural study was performed which confirmed the diagnosis of metastatic ESS. Satoh et al.^[9] emphasized the diagnostic dilemma of metastatic low-grade ESS in transbronchial fine-needle aspiration (FNA) cytology where the initial diagnosis was thought to be a non-neoplastic lesion. On surgical resection, a diagnosis of pulmonary endometriosis was considered due to the presence of bland and round to oval cells with positive expression for ER and PR. There was no previous history of gynecologic malignancy; however, a cytogenetic and FISH analysis demonstrated a t(7;17) translocation, which confirmed the diagnosis of ESS.

Ronen et al.^[5] reported a case of metastatic ESS in a patient who presented with multiple lung nodules. The FNA smears showed bland, oval to spindle cells with moderate cytoplasm, and delicate vessels, but no matrix component. The differential diagnosis included carcinoid tumor and diffuse neuroendocrine hyperplasia; however, the IHC stains for neuroendocrine markers were negative, and CD10 was positive. A definitive diagnosis could not be rendered because of the limited nature of the cytology specimen. The nodule was subsequently resected, and histology revealed tumor cells with smooth muscle differentiation and positive staining for ER, PR, and desmin. On further clinical investigation, a history of recent hysterectomy for fibroids at another hospital was obtained. On re-review of slides from the hysterectomy specimen, a small focus of low-grade ESS with similar morphology to the lung metastasis was noted confirming the diagnosis.

Mindiola-Romero et al.^[8] described a similar clinical scenario of low-grade ESS metastatic to the lung in a patient who presented with multiple lung nodules. A CT-guided core biopsy with rapid on-site assessment demonstrated cells with oval and spindled nuclei with mild-to-moderate atypia and scant matrix component. The core biopsy demonstrated bland spindle cells. Immunohistochemical workup for spindle cell neoplasms was performed using markers for desmin, S100, STAT6, CD34, and SOX-10 which were all negative. This prompted a molecular analysis that detected a fusion between exon3 of JAZF1 and exon 2 of SUZ12 supporting the diagnosis of low-grade ESS. Subsequently, immunohistochemical stains for ER, PR, and CD10 were positive corroborating the diagnosis. On further clinical investigation, the patient had a history of hysterectomy 25 years ago for ESS.

Metastatic low-grade ESS presenting as a solitary lung nodule as observed in our case is very rare. The predominance of small, round to oval cells with bland nuclei was thought to be consistent with a carcinoid tumor. Negative expression for neuroendocrine markers prompted review of the previous clinical history and additional IHC workup. Positive expression for ER, PR, CD10, and WT1 markers and a remote history of hysterectomy 26 years ago for endometrial sarcoma facilitated in making the right diagnosis. It must be emphasized that none of the above markers are specific for ESS; however, positive staining for WT1 has been shown to be a useful marker for differentiating extrauterine ESS from other potential mimics.^[11] IFITM1 is a novel marker for endometrial stroma cells with a higher specificity than CD10.^[12]

SUMMARY

This report highlights the diagnostic pitfall of metastatic LGESS in cytology specimens. The importance of clinical history and appropriate use of ancillary tests cannot be overemphasized. Awareness of the various cytomorphologic features and potential mimics is important.