American Thoracic Society(ATS) reported a comprehensive research about INSIP in 2008. Among the 193 cases of NSIP from published data, they found that only 67 cases were INSIP (34.72%), 28 cases of them were UIP (14.51%). Through which we can see it is difficult for clinicians and pathologists to distinguish INSIP from UIP. Histologicially, NSIP-F has a uniform pattern, characterized by expansion of the interstitium, a variable extent of chronic inflammation and fibrosis which can be collagenous or fibroblastic, lacking or scarcity of fibroblastic foci, primarily distinguishing it from UIP.
Our case showed various histological appearance of upper lobe. Not only was there the migration between NSIP-C and NSIP-F, but also the morphological appearance of NSIP and UIP coexisted in upper lobe. For example, formation of cystic fibrous gas cavity with fibroblast foci was hard to be differentiated from honeycomb, the latter and fibroblast foci were the morphological features of UIP. Besides, pathological appearance of middle and lower lobes showed the severe fibrosis and consolidation, formation of cystic gas cavity and alveolar structural remodeling and so on. Aforementioned pathological features render us hard to make a diagnosis of NSIP-F or UIP. Final diagnosis were based on the following points: (1) Without honeycomb change in chest CT scan, which conforming to NSIP-F; (2) Response to glucocorticoid to some extent; (3) Typical feature of NSIP in light fibrosis region; small fibroblast foci both in size and amount which occupied less than 10% of all slides, and looser collagen than myogelosis occurred in UIP. If the materials were all from only one lobe or the size of tissue was too small, the patient would possibly be misdiagnosed, or at least we would hardly make the diagnosis as NSIP-F or UIP.
How to make diagnosis when the histological pattern of NSIP coexists with UIP in multiple lobes biopsies? Flaherty et al.
] found that 26% of 109 patients had both the pattern of UIP and NSIP after analyzing several lobes of lung biopsy, so they thought as long as one lobe had the appearance of UIP, these patients should be diagnosed as UIP because of the poor prognosis of it. Recently, ATS/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin America Thoracic Society (ALAT) established the diagnosis guideline of IPF which concluded that some puzzling cases of IPF should be diagnosed based on combination with pathological information and HRCT
], and the appearance of honeycomb lung showed in HRCT is an important feature of UIP, whereas our case showed the pathological appearance of NSIP together with UIP, without honeycomb lung, so after a comprehensive analysis of all slides, we diagnosed our case as INSIP with UIP-like areas.
Differential diagnosis of INSIP includes drug induced lung injury
], the terminal stage of eosinophilic pneumonia and lung damage caused by environment exposure
]. However, our case had no usage of cytotoxic drugs and immunosuppressants, occupational and environmental exposure history. Thus it is easy to discriminate our case from above other diseases. Kirby et al.
] reported that 9 out of 28 recipients with renal allograft history who had pulmonary complications, including pulmonary hemorrhage, organizing pneumonia and pulmonary alveolar proteinosis, but no NSIP was found. We also excluded eosinophilic pneumonia, because our patient didn’t show an increasing number of eosinophile granulocytes in his peripheral blood and eosinophile granulocytes infiltrated in his lung lesions.
Histologicially, cystic fibrous gas cavity can be found in the whole right lung in our case, and the lesion almost existed in terminal stage of chronic lung disease. We assume that the obstruction of proximal bronchial results in extension of distal bronchial gradually, which may be the cause of the lesion, but the molecule mechanisms of the lesion are elusive. Besides, the metaplasia of bronchial was also a predominant feature in our case, some region even had hyperplasia of alveolar epithelium and abnormal expression of P53 (Figure
C). It has been reported that the patients with long-term chronic pulmanary fibrosis may developed into lung cancer and the atypical adenomatous hyperplasia of lung is related with the development of adenocarcinoma of lung
]. Of note, our case showed that the hyperplastic type alveolar epithelium had strongly positive expression of SP-A (Figure
B), which is a major player in the pulmonary cytokine-network and to act in the pulmonary host defense
], so further study is needed to detect the role of SP-A in the pathogenesis and prognostic evaluation of NSIP
In summary, we described one case of INSIP from gross to light microscopy for removed lung. Three main findings were as followings: (1) The existences of heterogeneity and transmigration between these subtypes of INSIP, if it is the case, the predominant appearance should be considered for diagnosis. (2) The metaplasia of bronchiole epithelium and formation of cystic fibrous gas cavity are also pathological characteristic of INSIP-F rather than features only for UIP. (3) It is possible for small fibroblastic foci to appear in INSIP, which means INSIP might also have UIP-like regions. In a word, the CRP diagnosis is the best way for such puzzling cases. In addition, it is worth noticing that if patient has terminal interstitial lung disease and need the surgery of lung transplantation, it should pay attention to the selection of recipients and postoperative care.