The mass was impinging on the supero-posterior surface of the liver (Figure 1). The lesion was seen closely abutting the descending aorta, right atrium, inferior vena-cava, right main pulmonary artery, right sided pulmonary veins, left inferior pulmonary vein and left atrium (Figure 1). There were multiple heterogeneously enhancing soft tissue pleural and parenchymal lesions seen in both lung fields, with the largest measuring approximately 4.2x2.3x1.9 cm. There were multiple heterogeneously enhancing lymph nodes seen in the pre-tracheal, para-tracheal and right hilar regions, with the largest measuring 1.8x1.5 cm. The liver measured 21.7 cm in its cranio-caudal extent with ill-defined hypodense areas and peripheral enhancement in segment VI. The CECT findings were suspicious for malignant etiology with lung, liver, bony and mediastinal nodal metastasis. Other investigations showed normal renal and liver function tests, normal thyroid function tests, non-reactive viral markers and normal coagulation studies. On the basis of the clinical and radiological inputs, a diagnosis of metastatic carcinoma involving the liver and lymph nodes with primary from the lung was considered. Complete blood count revealed anemia (Hemoglobin: 5.2g/dL), mild leukocytosis (14.02x103/cumm) and mild thrombocytosis (717x103/cumm). Peripheral smear showed no abnormal cells. Bone marrow examination was also performed and showed a fair number of plasma cells with a polyclonal pattern of distribution. In view of the above findings, serum protein electrophoresis was also done and no M band was seen. Under CT guidance, a core biopsy of right upper lobe lung nodule was done under local anaesthesia using an 18G biopsy needle (multiple cores measuring 1.0-1.7 cm). These core biopsies showed proliferation of bland spindle cells (Figure 2A), at places arranged in long fascicles, in an inflammatory background consisting of many plasma cells with scattered lymphocytes (Figure 2B-D). Native lung parenchyma was seen within the lesion. The closest differential considered was IgG4 related disease due to the bland nature of the spindle cells in the background of plasma cells. Other differentials such as leiomyosarcoma and mesothelioma were also considered but were ruled out due to the bland morphology and presence of inflammatory background. On IHC, these spindle cells expressed ALK (Figure 2E, F) and SMA (Figure 2K), whilst they were negative for desmin, cytokeratin, CD117, S-100 (Figure 2G-J), CD21 and IgG4 immunostain. ALK immunostaining was done on the Dako platform using monoclonal mouse anti-human CD246 antibody (clone ALK1) which showed focal positivity with weak intensity (Figure 2F). ALK immunostain was then also performed on the Ventana platform using monoclonal rabbit anti-human CD246 antibody (clone D5F3), which showed a higher proportion of cellular staining with higher intensity in the spindle cells (Figure 2E). A diagnosis of an inflammatory myofibroblastic tumor (IMT) of the lung was given. ALK gene re-arrangement by FISH (Florescent in-situ hybridization) was attempted but yielded a noncontributory result due to the exhaustion of the tissue block after performing the immunohistochemistry.
Following diagnosis, the patient was started on Crizotinib and has till date completed 3 months of therapy. CECT findings on comparison with the previous scan reveal interval reduction in the previously noted right lung mass and multiple lung nodules, now measuring approximately 10.9 (AP) x 9.5 (TR) x 8.6 (CC) cm (previously measured 12.9 (AP) x 11.9 (TR) x 9.6 (CC) cm) (Figure 1).
ALK-negative IMTs occurred in older patients and had greater nuclear pleomorphism, atypia, and atypical mitoses, and also metastasized widely. ALK reactivity was associated with local recurrence, but not distant metastasis, which was confined to ALK-negative lesions [5]. However, in our case all the features were seen along with involvement of the adjacent sites (liver, bone and lymph nodes). Complete resection of the tumor is considered the treatment of choice with the prognosis depending on the tumor size (less than or equal to 3 cm) and ALK reactivity [3,5]. In our case, the mass was large and hence chemotherapy was started as the treatment modality. Coffin et al. have concluded that ALK reactivity may be a favorable prognostic indicator in IMT [5]. Reduction in the size of the tumor (~2 cm) has been noted post 3 months of therapy, which points towards the positive ALK reactivity seen in this tumor. The overall 3-year survival rate is about 82% and the overall 5-year survival rate is about 74% [3,4].
This case posed a diagnostic challenge as the radiology and clinical picture was suggestive of malignancy and on histopathology only core biopsy was received on which the architecture of the lesion could not be appreciated. IMT is predominantly a morphological diagnosis based on the architecture of the spindle cells and is usually difficult to diagnose on core biopsies; a strong vigilance and indepth knowledge of this entity along with a wide variety of immunohistochemical markers therefore helps in reaching a conclusive diagnosis. The novel anti-ALK rabbit monoclonal antibody (D5F3 clone) demonstrates a much higher proportion of cell staining with a higher intensity, thus giving a superior overall performance of ALK protein in IMT.
CONFLICT of INTEREST
The authors declare no conflict of interest
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