Case 730 -- A 70 year-old male with multiple bilateral subcentimeter lung nodules

Contributed by Jessica Dwyer, MD and Sanja Dacic, MD, PhD


A 70 year-old male with a 55 pack/year cigarette smoking history, remote history of minimally invasive pancreatic adenocarcinoma, status post pancreaticoduodenectomy procedure in 2008, and superficially invasive esophageal adenocarcinoma diagnosed within the last month presented with multiple bilateral subcentimeter lung nodules, a prominent right upper lobe lung nodule, and a necrotic-appearing posterior mediastinal mass on a recent chest CT scan. A subsequent chest PET scan demonstrated increased uptake only in the posterior mediastinal mass. Fine Needle Aspiration (FNA) of the posterior mediastinal mass was attempted, but cytology was inconclusive.

The patient underwent resection of the posterior mediastinal mass and a right upper lung lobe wedge resection. Pathology received both specimens for intraoperative evaluation and diagnosis.

Grossly, the posterior mediastinal mass resembled an adherent conglomeration of lymph nodes measuring 4.5 x 3.7 x 2.0 cm in overall dimension. On sectioning, the mass parenchyma was nodular and heterogeneously tan-yellow with focal hemorrhage and necrosis. Figure 1 - Posterior mediastinal mass, Gross

Microscopically, the mass consisted of large collections of poorly differentiated and pleomorphic epitheloid cells with enlarged round to oval nuclei, diffuse chromatin with prominent nucleoli, abundant eosinophilic cytoplasm, and extensive necrosis. Figure 2 - Posterior mediastinal mass, frozen section

The right upper lung lobe wedge resection measured 3.0 x 1.5 x 1.0 cm in overall dimension. Within the grossly normal red-brown lung parenchyma was a well-circumscribed, firm, homogenous tan-white nodule measuring 0.9 cm in greatest dimension and located 0.3 cm from the staple line.

Microscopically, the neoplastic cells were morphologically similar to those of the posterior mediastinal mass but with a slightly more spindled appearance. Figure 3 - RUL nodule, frozen section

During consultation, it was determined that these two lesions were likely of the same process, but the origin of this presumed metastatic neoplasm could not be determined at the time of intraoperative evaluation. However, considering the patient's long history of cigarette smoking and history of two separate GI cancers, the differential diagnosis of these masses included poorly differentiated carcinoma of lung or GI origin, a lung neuroendocrine neoplasm, a sarcoma, or even melanoma.

Following permanent section, the morphology of both masses was re-evaluated. In addition to the aforementioned features of the neoplastic cells, focal abundant extracellular golden brown pigment and occasional cells with granular cytoplasmic brown-grey pigment were noted.

Figure 4 - Posterior mediastinal mass, permanent
Figure 5 - RUL nodule, permanent
Figure 6 - Posterior mediastinal mass with abundant pigment, permanent

The results of an immunohistochemical stain panel are as follows:

Figure 7 - Posterior mediastinal mass, permanent 40X
Figure 8 - Posterior mediastinal mass IHC, AE1/AE3 40X
Figure 9 - Posterior mediastinal mass IHC, S100 40X
Figure 10 - Posterior mediastinal mass IHC, HMB-45 40X
Figure 11 - Posterior mediastinal mass IHC, Melan-A 40X
Figure 12 - RUL nodule, permanent 40X
Figure 13 - RUL nodule IHC, AE1/AE3 40X
Figure 14 - RUL nodule IHC, S100 40X
Figure 15 - RUL nodule IHC, HMB-45 40X
Figure 16 - RUL nodule IHC, Melan-A 40X

Companion molecular analysis confirmed the masses were positive for the BRAF V600K mutation (GTG to AAG).

Figure 17 - Molecular report


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