Pulmonary Adenofibroma: Report of a Case with Multiple Masses
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1 Available online at Pulmonary Adenofibroma: Report of a Case with Multiple Masses Junmei Hao 1, Cuiping Zhang 1, Qinghua Cao 1, Jiarui Zou 1, and Chaofu Wang 2 1 Department of Pathology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong Province and 2 Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Abstract. We are reporting one case of multiple pulmonary adenofibromas in a 57-year-old non-smoking female. Ten well-circumscribed masses were identified in both lungs. The masses are characterized by glandlike structures lined by a single layer of simple cuboidal or columnar epithelium. The stroma is abundant and demonstrates compact spindle-cells. The epithelial component is generally positive for CK7, TTF-1, Napsin A. The stromal component displays expression of vimentin, desmin, SMA, h-cald, ER, PR, Bcl- 2, and is negative for CD34, CD117, CD99. We are postulating that the possible histogenesis of these lesions is via proliferation of mesenchymal component of the peribronchial wall, which entraps the epithelium as it expands. Hitherto, this is the first case with multiple lesions reported. Currently, the patient is 11 months post-surgery and doing well. Key words: Multiple, Pulmonary, Adenofibroma. 691 Introduction Pulmonary adenofibroma is a rare, benign biphasic tumor characterized by gland-like structures lined by simple cuboidal or columnar epithelium with abundant spindle-cell stromal component. The first case was described by Scarff et al. [1] in 1944, and only ten other cases displaying similar features have been reported since [2-8]. All previous cases represented non-specific clinical features and the median age of patients was 55 years (25-68 years). Also, these were all determined to be solitary pulmonary nodules radiographically. In our case, the patient has multiple pulmonary adenofibromas in both lungs, with the largest one demonstrating cavitation. For the purposes of this study, we describe the clinicopathological and immunohistochemical features of the tumor as well as the differential diagnoses and considerate treatments. Finally, we will attempt to further explore the histologic origins of these lesions. Address correspondence to Chaofu Wang, Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, , China; phone: ; e mail: ytfyblk@163.com Case report Our patient is a 57 year-old, non-smoking female presenting with a long history of cervical spondylosis. A health examination was subsequently performed in anticipation of her cervical vertebra surgery. The chest X-ray revealed a well-circumscribed nodule in the superior lobe of the left lung (Figure 1A). The CT scan showed ten small round nodules in both lungs, ranging in size from 0.2cm to 1.5cm. The largest nodule was located in the superior lobe of the left lung, close to the pleura (Figures 1B & C). Visceral cancer metastasis to the lungs was suspected, however, there was no evidence of another tumor. Video-assisted thoracoscopic exploration revealed a round subpleural mass within the lung parenchyma on the peripheral area of the left superior lobe. A wedge resection of the left superior lobe was performed for further evaluation. The patient was not given post-operative treatment. As of June 2016, the patient has been alive for 11 months without recurrence. Pathological findings. A cm portion of the left superior lung lobe was submitted for pathological examination. There were two round, well-circumscribed masses bulging within the pulmonary parenchyma. The larger mass measured cm was located under the pleura, and it demonstrated a cystic center (1.0 cm in /16/ by the Association of Clinical Scientists, Inc.
2 692 Figure 1. Chest X-ray revealed a well-circumscribed subpleural nodule in the superior lobe of the left lung (A). Contrastenhanced chest CT showed ten round nodules in both lungs, measured 0.2cm-1.5cm in dimension. The largest mass located in the superior lobe of the left lung, close to the pleural (B,C). diameter) filled with clear fluid. The smaller mass measured cm in size, and demonstrated a homogenous white-gray cut surface. Neither mass demonstrated necrosis or haemorrhage. Histopathologically, both masses are characterized by gland-like structures surrounded by abundant spindlecell stroma (Figures 2A & B). The gland-like structures are distributed irregularly as some are located peripherally. Additionally, the shape of the gland lumens are variable. Most of the spaces contain proliferating stromal cells projecting into dilated and elongated lumina, forming club-shaped or clefted structures. However, a smaller number of the spaces are more rounded. The epithelial cells lining in the spaces are cuboidal or columnar, with round or ovoid uniform nuclei and moderately abundant cytoplasm. Some of the cells also demonstrate inconspicuous cilia (Figure 2C). The stroma is evenly distributed throughout the tumor. It is hypercellular and composed of spindle cells arranged in intersecting fascicles (Figure 2D). The cells display cigar-shaped nuclei with small nucleoli and eosinophilic cytoplasm. A scattered lymphoid inflammatory infiltration in the stroma is observed, but collagen deposition is not apparent. No other mesenchymal components such as cartilage, fat or striped muscle are identified. Both the epithelial and stromal cells demonstrate bland nuclei, with no atypia or mitotic activity. Immunohistochemistry. Immunohistochemically, the epithelial component is positive for CK7, TTF-1 (Figure 3A) and Napsin A (Figure 3B), whereas the stromal component is positive for vimentin (Figure 3C), desmin, SMA, h-cald (Figure 3D), ER, PR, Bcl-2, and is negative for CD34, CD117, CD99. Discussion The diagnosis of pulmonary adenofibroma is based entirely on histopathological and immunohistochemical evaluations; epithelial cells are persistently positive for CK, TTF-1, EMA, whereas stromal cells show variable degrees of positive immunostainings for vimentin, desmin, CD34, Bcl-2, CD99, SMA [8]. However, even though the diagnosis of these lesions is established, the histogenesis is not. Scarff et al. [1] commented that the tumor probably belongs to the same family of cartilaginous hamartoma of the lung. However, they also considered the possibility of the tumor originating from a fibroma growing in a lobular fashion with the epithelial element becoming secondarily entrapped. Suster et al. [3] contended that the lesion represents an immature form of pulmonary hamartoma. They postulated that the core of the lesion
3 Pulmonary adenofibroma 693 Figure 2. Histopathology of the two masses. The smaller one (A: H&E, 40 ), and the larger one with a cystic degeneration (B: H&E, 20 ). The tumor is characterized by gland-like structures surrounded by compact spindle-cell stroma, and the epithelial cells are cuboidal or columnar (C: H&E, 200 ); the stroma is hypercellular and is composed of spindle cells arranged in intersecting fascicles (D: H&E, 200 ). was composed of uncommitted fibroblastic mesenchymal element with no capability to differentiate into more specialized elements such as cartilage, smooth muscle or fat. Cavazza et al. [4] and Sironi et al. [5] interpreted the tumor as an adenofibromatous/papillary variant of a solitary fibrous tumor (SFT). In their experience, the stroma stained positively for CD34, Bcl-2, and CD99. In 1970, based on the studies of pulmonary hamartomas, Bateson [9] concluded that such tumors were formed by the proliferation of mesenchymal components of the bronchial wall that entrap the overlaying epithelium. A similar conclusion was made by Perez-Ataide [10]. They postulated that such lesions originated from peribronchial connective tissue and respiratory epithelium. In our case, based on the histopathological and immunohistochemical features described previously, we believe that the surface epithelium is similar to peribronchial type and the stroma component has a differentiation of smooth muscle. Furthermore, we postulate that these lesions originate from peribronchial wall tissue and the overlying respiratory epithelium, as suggested by Bateson [9] and Perez- Ataide [10]. Pulmonary adenofibroma can be distinguished from other benign and malignant tumors with a biphasic pattern. First, we will consider pulmonary hamartoma. As the most common benign neoplasm of the lung; the tumor is composed of varying amounts of at least two mesenchymal elements
4 694 Figure 3. Immunophenotype of the tumor. The epithelial cells are strongly positive for TTF-1 (A: En Vision, 100 ) and Napsin A (B: En Vision, 100 ); the stromal cells are positive for vimentin (C: En Vision, 100 ) and h-cald (D: En Vision, 100 ). such as cartilage, fat, connective tissue, and smooth muscle. Entrapped respiratory epithelium is also needed in addition to the mesenchymal elements. This can be distinguished from pulmonary adenofibroma by the presence of two or more mesenchymal components. Solitary fibrous tumor (SFT) is another tumor that can be confused with pulomary adenofibroma. Cavazza et al. [4] and Sironi et al. [5] described pulmonary adenofibroma as a variant of SFT; however, we believe they are different tumor entities. SFT is a ubiquitous mesenchymal tumor of fibroblastic type. It is characterized by a combination of hypocellular and hypercellular areas separated by thick bands of hyalinized, sometimes keloidal, collagen with thin-walled branching vessels. When this occurs in the lung, it may entrap normal respiratory epithelium at the periphery in a haphazard arrangement as opposed to the diffused distribution and complex arrangement of the glandular epithelial element in pulmonary adenofibroma. Next, we will differentiate pulmonary adenofibroma from some malignant tumors; such as synovial sarcoma, pulmonary blastoma, and metastatic lung tumors. Lung is the most common organ-based site for synovial sarcomas. Biphasic synovial sarcoma is also characterized by variable mesenchymal and epithelial component. However, it demonstrates a specific chromosomal alteration t(x; 18) (p11; q11), resulting in the fusion of SYT- SSX genes [11,12]. The tumor cells are atypical and necrosis is present in most cases. Pulmonary blastoma is a rare, malignant pediatric tumor composed of malignant mesenchymal cells and native epithelial cells. The stromal component is heterogeneous, and such tumor tends to be large with frequent areas of haemorrhage and necrosis. Some metastatic
5 Pulmonary adenofibroma 695 tumors, such as phyllodes tumor of the breast, may also mimic pulmonary adenofibroma, but they usually appear as multiple masses or nodules. The histological features are similar to those of the primary lesions and the immunohistochemical appearance is that of the primary tumors. Pulmonary adenofibroma carry a good prognosis. At the time of this paper, there are no recurrent or metastatic cases reported. There are many methods for definitive diagnosis of the lesion including fiberoptic bronchoscopy, transthoracic needle aspirate, surgical resection by thoracotomy, and video-assisted thoracoscopic surgery (VATS). After comparing these different methods, Wang Y et al. [6] concluded that VATS is the best diagnostic and therapeutic modality. Its benefits include lower perioperative morbidity and a shorter hospital stay. Intraoperative frozen-section consultation can also be a valuable adjunct in treatment planning [8]. In our patient, there are ten total nodules in both lungs. Two nodules were resected by VATS and the other eight lesions were left in lungs after diagnosis. The patient was not given any post-operative treatment. She continues to remain well with no evidence of recurrence and development 11 months postoperatively. In conclusion, we are presenting a report of multiple pulmonary adenofibromas, which has not been reported previously. We also postulate the histologic origin of these lesions. Final diagnosis depends on histopathological characteristics of the tumor. A definite diagnosis is needed to plan therapy and avoid inappropriate and unnecessary surgical intervention. References 1. Scarff R.W., Gowar F.J.S.. Fibroadenoma of the lung. The Journal of Pathology and Bacteriology 1944; 56: Butler G, Kleinerman J. Pulmonary hamartoma. Arch Pathol 1969; 88: Suster S, Moran CA. Pulmonary adenofibroma: report of two cases of an unusual type of hamartomatous lesion of the lung. Histopathology 1993; 23: Cavazza A, Rossi G, De Marco L, Putrino I, Pellegrino S, Piana S. Solitary fibrous pseudopapillary tumor of the lung: pulmonary fibroadenoma and adenofibroma revisited. Pathologica 2003; 95: Sironi M, Rho B, Spinelli M. Adenofibromatous pattern in a solitary fibrous tumor of the lung. Int J Surg Pathol 2005; 13: Wang Y, Xiao HL, Jia Y, Chen JH, He Y, Tan QY, Zhang W.G.. Pulmonary adenofibroma in a middle-aged man: report of a case. Surg Today 2013; 43: Vitkovski T, Zeltsman D, Esposito M, Morgenstern N. Pulmonary adenofibroma: cytologic and clinicopathologic features of a rare benign primary lung lesion. Diagn Cytopathol 2013; 41: Kumar R, Desai S, Pai T, Pramesh CS, Jambhekar NA. Pulmonary adenofibroma: clinicopathological study of 3 cases of a rare benign lung lesion and review of the literature. Ann Diagn Pathol 2014; 18: Bateson EM. Histogenesis of intrapulmonary and endobronchial hamartomas and chondromas (cartilage-containing tumours): a hypothesis. J Pathol 1970; 101: Perez-Ataide AR, Seiler MW. Pulmonary hamartoma. An ultrastructural study. Cancer 1984; 53: Yaseen SB, Mustafa F, Rafiq D, Makhdoomi R, Chanda N. Primary pulmonary synovial sarcoma: Diagnosis on squash smears. J Cytol 2015; 32: Karpathiou G, Stefanou D, Froudarakis ME. Pleural neoplastic pathology. Respir Med 2015; 109:
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