Acantholytic squamous cell carcinoma of the lung with marked lymphogenous metastases and high titers of myeloperoxidase-antineutrophil cytoplasmic antibodies: a case report

Abstract

Background: Acantholytic squamous cell carcinoma (ASQCC), histologically characterized by intercellular bridge loosening, is recognized as a rare variant of squamous cell carcinoma (SQCC). ASQCC may demonstrate a worse prognosis than conventional SQCC. Pulmonary ASQCC is particularly rare; its biological behavior and prognostic data have not been reported.

Case presentation: We report the clinical and autopsy findings of a 71-year-old Japanese man with pulmonary ASQCC. Pulmonary lesions, suggestive of idiopathic interstitial pneumonia, were radiologically observed 3 and 6 years prior to the patient's most recent hospitalization; however, the patient did not undergo further medical examinations. Upon being discovered unconscious, the patient was admitted to our hospital. Dehydration and lower limb muscle weakness were noted, as were laboratory findings of coagulation abnormalities and renal dysfunction. Computed tomography helped confirm a 21-mm peripheral nodule in the upper left lobe of the lung, with associated swollen lymph nodes in the bilateral hilar, mediastinal, and para-aortic regions. Brain and spinal lesions, suggestive of neurological disturbances, were not found. Small cell lung carcinoma was suspected, upon admission, but high serum levels of squamous cell carcinoma antigen and cytokeratin-19 fragments were present. Therefore, advanced lung cancer, possibly SQCC, was diagnosed. The patient was treated with best supportive therapy, and died one month after admission. Hypercalcemia and high serum levels of parathyroid hormone-related protein (PTHrP) and myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) titers were observed. Progressive renal insufficiency was absent due to improved renal function subsequent to hydration. An autopsy helped confirm the left lung tumor as an ASQCC associated with pulmonary lymphangitic carcinomatosis and multiple metastases in the lungs and lymph nodes. Skin lesions suggesting malignant tumors were absent. The metastatic lesions consisted largely of acantholytic tumor cells, and the lungs showed usual interstitial pneumonia pattern; vasculitis was absent.

Conclusions: This is the first reported case of pulmonary ASQCC resulting in an aggressive clinical course, with marked lymphogenous metastases and PTHrP-associated hypercalcemia. The high serum MPO-ANCA titers were clinicopathologically insignificant, but may have been related to the pulmonary interstitial lesion. Pulmonary ASQCC represents a highly malignant subset of lung cancer.

Keywords: Acantholytic squamous cell carcinoma; Hypercalcemia; Lymphogenous metastasis; Myeloperoxidase-antineutrophil cytoplasmic antibody; Parathyroid hormone–related protein; Small cell lung carcinoma; Squamous cell carcinoma.

Fig. 1

Radiologic images of the tumor and brain. a–b Axial computed tomography images show a 21-mm, solid, pulmonary nodule in the left upper lobe (a), arrow) and swollen mediastinal lymph nodes (b), arrow). c The axial diffusion-weighted magnetic resonance image shows a tiny high-intensity area (arrow) near the right-side ventricle in the cerebrum. Bars indicate 5 cm

Fig. 2

Autopsy and pathologic findings of the acantholytic squamous cell carcinoma of the lung. a An axially cut section of left lung shows the upper lobe tumor (an arrow) and hemorrhagic lower lobe. b Axially cut sections (numbers 1–8) of the mediastinum demonstrate metastatic lymph nodes (arrows) in the ipsilateral and contralateral sides. Stars indicate airway of the trachea and its bifurcation. The numbered, dotted lines correspond to the numbers of the cut sections. c–d The left upper lobe tumor includes pseudoacinar nests containing discohesive atypical cells. Individual atypical tumor cells are also seen in the stroma (d). e–i The monomorphic and discohesive tumor cells that are associated with squamoid cells or nests (e) show filling in some alveolar spaces (f), pulmonary lymphangitis carcinomatosis (g), left, low magnification; right, D2–40 immunostained section), and lymph node metastasis (h) and its inset, high magnification of (h). The papanicolaou-stained smears (I) prepared from bilateral pulmonary effusion confirm acantholytic tumor cells including signet-ring cells (arrow) that are also seen in (f) (arrow). Images of (c–h) are taken from sections stained with hematoxylin and eosin. Bars indicate 3 cm in (a–b), 100 μm in (c–f), and (i), and 1 mm in (g) and (h)

Fig. 3

Immunohistochemistry of the acantholytic squamous cell carcinoma of the lung. a The pleomorphic tumor cells are diffusely positive for cytokeratin 5 (CK5). b–e The monomorphic, acantholytic tumor cells, mainly seen in lymphatic duct of the bronchial wall, are diffusely positive for CK5 (b) and p40 (c) and almost negative for vimentin (d). The acantholytic tumor cells are largely positive for E-cadherin (e), but the low intensity of the cellular membrane is notable (inset, high magnification of (e). The bronchial epithelium (left side of (b–e) is an internal positive control for CK5 (b), p40 (c), and E-cadherin (e) and the bronchial stromal cells are internal positive controls for vimentin. Bars indicate 100 μm