In situ follicular neoplasm discovered as an enlarging pulmonary nodule complicated by pulmonary aspergillosis

Abstract In situ follicular B cell neoplasm, previously known as follicular lymphoma in situ, is a neoplastic proliferation of follicular lymphoma‐like B cells confined to the germinal centers. Herein, we report a case of a woman in her 70s who initially presented with several enlarged abdominal lymph nodes. Seven months later during follow‐up, a solitary pulmonary nodule was detected. As it was close to the hilum, lobectomy was performed. The intraoperative frozen section showed fibrosis and a collection of lymphocytes and macrophages. Therefore, the lymph nodes were sampled. Station 4 and 10 lymph nodes exhibited similar tumor cells and were immunohistochemically positive for CD10 and BCL2. Thus, the patient was diagnosed with in situ follicular neoplasm and is currently under observation. In situ follicular neoplasm is typically a slowly progressive neoplasm; however, it can present as a rapidly enlarging pulmonary nodule complicated by pulmonary aspergillosis.


INTRODUCTION
In situ follicular neoplasia (ISFN) is a neoplastic proliferation of follicular lymphoma-like B cells confined to the germinal centers. Occasionally, it is detected as an incidental finding following lymph node resection for another lesion. 1 The previously described follicular lymphoma (FL) in situ has now been reclassified as ISFN according to the 2017 World Health Organization classification. 1 ISFN diagnosis based on imaging information alone is difficult, even though it is described as a benign tumor.
Herein, we report a case of ISFN in a patient who underwent pulmonary resection for a pulmonary nodule for which no definitive diagnosis had been made.

CASE REPORT
A woman in her 70s with a suspected pancreatic cyst was referred to the gastroenterology department at our institute.
Abdominal ultrasound revealed no pancreatic cyst; however, several enlarged intra-abdominal lymph nodes with nonspecific inflammatory changes were visualized. Chest computed tomography (CT) performed 4 months later did not show any apparent nodules; however, a repeat CT performed 7 months after detected a 1 cm lung nodule ( Figure 1). The nodule had a standardized uptake value of 2.24 on 18Ffluorodeoxyglucose positron emission tomographic (PET) imaging. There were no other nodules with abnormal standardized uptake. The patient was referred to our department for surgical biopsy and resection. The patient's general condition was unremarkable; however, the renal function was mildly disturbed (creatinine, 0.82 g/dL; estimated glomerular filtration rate, 51 mL/min). Thoracoscopic upper lobectomy of the right lung was performed. A needle biopsy or partial resection should have been performed to confirm malignancy by rapid pathology, followed by anatomical lobectomy; however, both methods were deemed difficult because of the proximity of the nodule to the pulmonary hilum; thus, lobectomy was performed with four-port complete thoracoscopic surgery and was completed with no complications.
The intraoperative frozen tumor section showed only fibrosis and lymphocyte and alveolar macrophage collections instead of malignant changes; thus, the lymph nodes were sampled. The postoperative course was uneventful. The results of the pathological examination revealed an Aspergillus-like fungal mass in the center of the tumor. The surrounding area was infiltrated by lymphocytes forming numerous lymphoid follicles. Based on several immunostaining results, ISFN, previously known as in situ FL, was diagnosed ( Figure 2). Both station 10 and 4 lymph nodes had similar tumor cells, and station 4 lymph nodes showed a disorganized distribution of germinal centers in the tumor. The patient has currently been under postoperative observation for 30 months.

DISCUSSION
This case demonstrates two important points. First, in situ follicular neoplasm can manifest as a rapidly enlarging pulmonary nodule. In the present case, enlarged lymph nodes were already observed in the abdominal cavity; however, they did not change significantly during the disease. The pulmonary nodule was observed on the follow-up CT. The interval between the first CT scan when no nodules were observed, and the second CT scan when they were observed, was 3 months, indicating a fast growth rate. ISFN is described as a slow-progressing tumor, but the pulmonary nodule in the present case had an extremely fast growth rate. When pulmonary nodules rapidly increase in size, as in this case, the differential diagnosis is infection or malignancy rather than a benign tumor or ISFN. Moreover, in the current case, the pathological examination revealed an Aspergillus-like fungal mass in the resected specimen. Therefore, pulmonary aspergillosis should be included in the differential diagnosis of the enlarged pulmonary nodules, which could explain the absence of enlarged intraabdominal lymph nodes. Furthermore, if ISFN had been considered in the differential diagnosis, a definite diagnosis would require resection. 1 ISFN does not require aggressive treatment; however, careful follow-up is needed. The rate of ISFN observed in resected lymph nodes is approximately 2%-3%, and the frequency of progression to overt FL is <5%. [2][3][4][5] In this case, the preoperative PET did not indicate metastasis of ISFN; however, it was observed both in the pulmonary nodule and sampled lymph nodes. This indicates that ISFN cells can metastasize lymphatically throughout the body. Cells may be found in the blood and lymph nodes throughout the body in ISFN cases. 5 Metastasis implies that the disease will recur or increase in size, as in thymoma, and it may even transform into FL. The accurate differentiation between the ISFN and FN is challenging but of great importance to avoid overtreatment 6 ; therefore, careful follow-up is necessary.