INTRODUCTION: Lymphangitic carcinomatosis (LC) secondary to squamous cell carcinoma (SCC) of the cervix (SCCC) is exceedingly rare. In prior reports, LC coincided with significant abdominal and thoracic lymphadenopathy. Additionally, sputum cytology, bronchial washings and/or transbroncheal biopsies represented successful diagnostic modalities (3). We report a case of LC secondary to SCCC in a patient immunocompromised due to chemoradiation presenting with diffuse bilateral pulmonary infiltrates and hypoxic respiratory failure. Importantly, there was no thoracic, abdominal, or pelvic lymphadenopathy. In addition, multilobar bronchioalveolar lavage (BAL) and transbronchial biopsies were non-diagnostic. Subsequently, open lung biopsies were consistent with LC.
CASE PRESENTATION: A 38-year-old white female presented with a two-month history of worsening dyspnea associated with productive cough, subjective fever, and bilateral pulmonary infiltrates on chest X-ray. She was diagnosed with stage III locally advanced SCCC sixteen months prior. On presentation, she was in remission after having undergone total hysterectomy, adjuvant platinum-based chemotherapy, and radiotherapy. Her physical examination revealed respiratory distress, oxygen saturation of 88% on room air, and bilateral diffuse inspiratory crackles. CD4 count was 240; HIV serology, p24, and PCR were negative. A CT scan of the chest showed diffuse centrilobular ground glass opacities with interstitial and peribronchial thickening. Importantly, there was no radiographic evidence of thoracic, abdominal, pelvic lymphadenopathy or masses. Cultures, serology, BAL, and transbronchial biopsies were negative for infection and inflammatory disease. In addition, neither transbronchial biopsies nor BAL fluid cytology revealed any malignant cells. Based on the severity of the patient’s symptoms and lack of diagnosis, an open lung biopsy was performed. Unexpectedly, this demonstrated neoplastic sheets of cells with squamous morphology features along the perivascular, peribronchial, and subpleural lymphatic vessels as well as in pulmonary arterioles. Immunohistochemical analysis was strongly positive for p16 (a marker used to differentiate between primary pulmonary and cervical SCC) and cytokeratin (CK)-7, while negative for CK20, p63 and thyroid transcription factor 1, findings consistent with a diagnosis of LC from SCCC (1). Unfortunately, due to extend of pulmonary tumor burden, the patient was not extubatable after the lung biopsy, and care was withdrawn.
DISCUSSION: SCCC spreads most frequently by direct extension to the surrounding tissues. Pulmonary metastasis in form of LC, though rare, indicates advanced metastatic disease with a grave prognosis. Its non-specific clinical manifestations (e.g. cough, dyspnea) often lead to an incorrect diagnosis (e.g. pneumonia, or congestive heart failure). The mechanism of SCCC metastasis in form of LC is poorly understood. The significant involvement of hilar lymph nodes in previously reported cases suggests tumor cell invasion through the lymphatic channels, with proliferation in hilar lymph nodes leading to obstruction of lymphatic flow, and subsequent retrograde spread of tumor cells within the pulmonary lymphatics. However, our case suggests an alternative mechanism, as there was no radiographic evidence of abdominal or thoracic lymph node involvement. This suggests potential other routes of tumor spread, such as hematogenous tumor microembolization to the pulmonary lymphangitic system (2). Our patient’s immunocompromised condition from recent chemoradiation may have facilitated such a process by allowing tumor cells to escape from immunosurveillance (2). A second significant finding of our case is the non-diagnostic result of multilobar BAL and transbronchial biopsies despite the diffuse bilateral lung involvement.
CONCLUSIONS: Our case is the first report of a misleading presentation of LC from SCCC in an immunocompromised host in the absence of thoracic, abdominal or pelvic lymphadenopathy with nondiagnostic BAL and transbronchial biopsies. A high clinical suspicion and aggressive diagnostic strategy are needed for pulmonary abnormalities in patients with a history of SCCC, especially if immunocompromised.
Reference #1 Wang CW. Am J Clin Pathol 2009.
Reference #2 Shin MS. Invest Radiol 1995.
Reference #3 Storck K. Gynecol Oncol 2004.
DISCLOSURE: The following authors have nothing to disclose: Amir Emtiazjoo, Tim Lahm, Francis Sheski
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