Typical pulmonary hamartomas are usually composed of cartilage, fat, fibers or smooth muscle, and was often accompanied by bronchial/alveolar epithelial invagination. However, rare pulmonary hamartomas show different tissue forms because of a lack or difference proportion of certain components, so different pathological names appear in pathology: 1,FCL (Complete Cartilage Deficiency Type); 2,PLH; 3,PFLH. the PFLH is only composed of fiber and smooth muscle tissue and invaginated respiratory epithelium. The lesion is often adjacent to the bronchioles or thick wall vessels, or has thick wall vessels or bronchial epithelium penetrating into the leision[3]. In our case, the bronchial epithelium extended into the alveolar septa in the pulmonary parenchyma without a cartilaginous or adipose element. the lesion may be solitary or multiple in single or double lung, may occur in any part of the lung parenchyma, even occur in the bronchus with polypoid blocking of the bronchial lumen [4]. Three cases reported in this group had single and multiple, all occurred in the lung parenchyma. Patients with the lesions are generally asymptomatic or only non-specific respiratory symptoms such as cough, expectoration and so on. Most of them were found in physical examination or other diseases. Imaging findings are usually solitary or multiple nodules of different sizes in the lung with smooth edges. usual lesion nodule diameter range 2–55 mm, Multiple lesions occur more frequently than solitary lesions, and the tumors are more prevalent in women, however, in China, more prevalent in men (more men cases was reported).
Hull MT et al[5] reported a female case who had not a history of uterine leiomyoma, and Sugawara M et al. [6] reported a case of a 9-year-old girl, two cases’ lung neoplasms are polyclonal value-added, So somebody think that PFLH may not be a real tumor though it fits a tumor that form a clear boundary Morphologically. Tietze et al[7] found that some so-called“PFLH” and uterine smooth muscle tumors come from the same clone with comparative genomics hybridization and X chromosome inactivation analysis,Therefore, the authors believed that these tumors may not be true Pulmonary primary fibroleiomyomatous hamartomas but the metastasis of uterine leiomyoma. Horstmann JP[8] report a woman diagnosed with PFLH during her pregnancy, interestingly, the pulmonary nodules regressed after pregnancy and lactation. It indicates that the nodules was hormone dependent. Therefore, the author think Immunohistochemical markers such as ER,PR combined with history and gynecological examination could help to identify it. At present, there are few molecular pathology studies on PFLH. Of course, generally, polyclonal leision rarely check common genes such as KRAS gene, EGFR gene mutation [9].
PFLH usual has been considered benign leision, However, Sugawara M et al [6] reported that one of the nodules grew rapidly after 12 years of follow-up in a patient with multiple PFLH in both lungs, the tumor showed dysplasia, and KI67 value-added index increased. The case 2nd in this group have a history of lung adenocarcinoma, and more nodules were found after 5 months secondary surgery in CT the chest, More case studies are needed if oncogene mutations are associated with PFLH. Besides, PFLH can also have heterogenous metaplasia, Kato N[10] reported a case of multiple PFLH secondary osteogenesis, The patient had a history of parosseous osteosarcoma, For the exclusion of metastatic tumors, the authors performed clonal analysis of human androgen receptor gene targets, The results showed that pulmonary nodules were polyclonal.
PFLH’s diagnosis mainly depends on pathological examination, it needs to be distinguished from FCL, PFA, PPL, PML, BAA and SFT. FCL is also called chondrogenic pulmonary hamartoma which is the most common benign tumors in the lung and consisting of insular cartilage, fat, smooth muscle, and overlying respiratory epithelium, while PFLH has no cartilage, fat, and mucus tissue; PFA is a benign biphasic tumor and composed of epithelial and stromal components that like the fibroadenoma of female genital tract or fibroadenoma of the breast, Immunohistochemical marking the epithelial component was positive for CK and TTF-1,and the stromal component expressed desmin and SMA focally[11]. PPL is vey scarce, and it usually occurs in parenchymal, endotracheal, or endobronchial sites[12]. Endobronchial leiomyoma accounts for 33% of primary pulmonary leiomyoma[ 13] and no epithelial invagination. However, PML usually occurs in women with a history of uterine leiomyoma. BAA is a well-defined polycystic mass, separated by dilated spaces separated by fibrous intervals of varying thickness. The larger capsule in the center contains eosinophilic granular material which is positive with PAS staining, and the surface of the capsule is covered with alveolar cuboidal cells. The stroma is myxoid matrix of fusiform cells. Immunohistochemical staining showed CK, TTF-1-positive in the epithelial and SMA-focal-positive in the interstitial cells [14]. SFT showed expansive growth with clear boundaries and rare respiratory epithelial invagination. Microscopic examination revealed short spindle-shaped or oval cells with bundles and matted arrangement. cells were alternately distributed in loose and dense areas and the stroma was rich in collagen in the classic SFT [15]. However, the clinicopathological spectrum of SFT has been ever-expanding in past dedecades, the incorporation of cases includes myxoid, giant cell-containing, and fat-forming histology, as well as those from extrathoracic sites, including the meninx.immunohistochemical markers CD34, STAT6- positive and CK SMA,Desmin- negative[16]. Especially, The derived immunohistochemical detection of nuclear STAT6 expression has high diagnostic value in distinguishing SFTs from histologic mimics[17]. Therefore, though it is difficult to distinguish PFLH with SFT in imaging, it is differentiated easily in pathology.
PFLH is a rare lung leision, most cases reported in the literature was rare relapses, so far. complete resection alone seems to be a suitable surgical treatment. Some endobronchial lesions can also be removed by bronchoscopy to relieve surgical pressure.