Clara So,Takeshi Ushigusa,Torahiko Jinta
Cavitary lung metastases of mixed metaplastic breast cancer mimicking aspergilloma
pulmonary metastasis,metaplastic breast cancer,cavity,computed tomography,aspergilloma
Abstract We report a case of a 57‐year‐old woman with pulmonary metastasis of breast cancer presenting with a characteristic cavitary shadow resembling aspergilloma. The primary tumor and metastases showed multiple histopathologic components, including squamous cell carcinoma. Although a fungal ball‐like shadow may indicate the presence of a pulmonary aspergilloma, a comprehensive examination, including bronchoscopy, should be considered.
Cavitary lung metastases of mixed metaplastic breast cancer mimicking aspergilloma

We report a case of a 57‐year‐old woman with pulmonary metastasis of breast cancer presenting with a characteristic cavitary shadow resembling aspergilloma. The primary tumor and metastases showed multiple histopathologic components, including squamous cell carcinoma. Although a fungal ball‐like shadow may indicate the presence of a pulmonary aspergilloma, a comprehensive examination, including bronchoscopy, should be considered.

Metaplastic breast cancer (MBC) is an uncommon and aggressive form of cancer that has a worse prognosis than other triple‐negative invasive ductal carcinomas. It accounts for less than 1% of all breast cancers. , According to the National Institutes of Health, there are no known risk factors for MBC. Only four cases of metaplastic breast carcinoma with pulmonary metastasis have been reported. , The radiological features of such cases are still unknown. We report a case of a 57‐year‐old woman with pulmonary metastasis of breast cancer presenting with a characteristic cavitary shadow resembling aspergilloma. We discuss the mechanisms that led to the characteristic imaging, along with histopathological findings.

A 57‐year‐old woman came to our department for the evaluation of abnormal shadows on a chest radiograph during her regular check‐up. She had a history of stage IIA (T2N0M0) right breast cancer resection 3 years before. Postoperative examination showed MBC with squamous and spindle cell features and with triple‐negative (estrogen, progesterone, and HER2 receptor‐negative) phenotype. She received 12 cycles of paclitaxel therapy and four cycles of dose‐dense doxorubicin and cyclophosphamide as postoperative chemotherapy. Thereafter, she underwent CT scans every 6 months. At an outpatient visit 2 years and 6 months after completion of adjuvant chemotherapy, computed tomography (CT) showed post‐right mastectomy changes for breast cancer, but no findings to suggest local recurrence. There was no mediastinal, axillary or internal thoracic lymphadenopathy. Multiple lesions with thick‐walled cavities were observed in the right lung apex (Figure 1a), right upper lung S2/3 (Figure 1b), and right lower lung S9 (Figure 1c), some of which contained fungus ball‐like masses with spiculated pleural depression and pneumothorax. She was a nonsmoker and had no pulmonary symptoms. Sputum culture test revealed Mycobacterium avium complex, after which combined antibiotics administration was started. However, because the lung lesions rapidly progressed, a transbronchial biopsy was performed. Histopathology showed a mixture of epithelial and spindle cell components with a distinct keratinizing tendency, morphologically coincident with the known MBC diagnosed 3 years before (Figure 1d). Immunostaining showed that the tumor was CK14+, CK5/6+, CK34βE12+, p63+, GATA3+, estrogen‐ (Allred PS0 + IS0 = TS0), progesterone‐ (Allred PS0 + IS0 = TS0), and HER2‐ (score 0). Considering these results, her medical history, and clinical information, we diagnosed lung metastases of mixed MBC. Tissue culture was negative, and Ziehl‐Neelsen and Grocott stains were also negative.

MBC is characterized by large tumor size, rapid growth, and a high potential for metastatic spread through vasculature. Thus, the lung and bones are the most common sites of MBC metastasis. They are characterized morphologically by neoplastic epithelial or mesenchymal differentiation. The most common epithelial variant is squamous cell carcinoma, while tumors with mesenchymal differentiation can present with spindle cell, cartilage, or bone proliferation. Metaplastic carcinoma of the breast is currently classified into six subtypes: (1) low‐grade adenosquamous carcinoma, (2) fibromatosis‐like metaplastic carcinoma, (3) spindle‐cell carcinoma, (4) squamous cell carcinoma, (5) metaplastic carcinoma with heterologous mesenchymal differentiation, and (6) mixed metaplastic carcinoma. This case was characterized as mixed metaplastic carcinoma, with both squamous and spindle cell features. Aspergilloma is a fungus ball caused by Aspergillus sp., which is usually found in patients with cavitary lung disease. The fungus's hyphal form invades the pulmonary vasculature, leading to pulmonary hemorrhage, arterial thrombosis, and eventual infarction. Leukocytes eventually reabsorb necrotic tissue in the periphery, causing the infarcted center to retract and form a devitalized tissue at the center. The ball‐in‐hole sign appears when air fills the gap between the devitalized tissue and surrounding parenchyma. Clinicians must be cautious in their differential diagnosis based on radiologic findings, as this sign can be found in both infectious and noninfectious diseases. , At least six mechanisms have been proposed to explain cavity formation in metastatic pulmonary lesions: (1) central degeneration, especially in cases of keratin‐producing squamous cell carcinomas; (2) ischemic necrosis due to thrombosis of arteries supplying the tumors; (3) central necrosis caused by inadequate blood supply and by infection as tumors grow; (4) the tendency of mucin‐secreting adenocarcinomas to form cysts from the primary tumors in the ovary, breast, or gastrointestinal tract; (5) formation of cystic air spaces resulting from an intermittent check‐valve obstruction of a bronchiole; and (6) a thin layer of malignant cells growing into a pre‐existing cavity or cyst. Our patient presented with a cavitary shadow with fungal ball‐like masses on CT, confirming both spindle and squamous cell carcinoma components. We presume that pulmonary cavitation can occur through a combination of factors: the most plausible mechanism of cavity formation, in this case, might be the degeneration secondary to keratin production of squamous cell carcinomas. When evaluating patients with lung cavitary mimicking aspergilloma, comprehensive examination including bronchoscopy should be considered to avoid misdiagnosis and delaying treatment. Reconfirming the histopathology of primary and metastases sites is useful.

The authors declare that they have no competing interests.

Written informed consent was obtained from the patient for the publication of this manuscript and the accompanying images.