Pulmonary lymphangitic carcinomatosis from head and neck squamous cell carcinoma

Abstract

Pulmonary lymphangitic carcinomatosis (PLC) secondary to mucosal head and neck squamous cell carcinoma (HNSCC) is extremely rare, difficult to diagnose in the pre-symptomatic phase, and is rapidly fatal. We describe two cases of fatal PLC secondary to squamous cell carcinoma in whom a review of pre-treatment imaging (computed tomography of the chest) changes reported as unspecific were retrospectively felt to be consistent with pre-symptomatic PLC. Case 1, a 73-year-old male with T2N2bMx poorly differentiated squamous cell carcinoma of the right tonsil, died 6 weeks after chemoradiotherapy with curative intent. Case 2, a 65-year-old female with T4aN2bMx of the right body of the mandible, died within 6 weeks of radical surgery including free tissue transfer. A review of the literature showed that PLC secondary to HNSCC occurs in an older cohort of patients: mean age 69 years vs. other tumour groups 50 years. PLC secondary to HNSCC can behave in distinctly different ways, demonstrating similarity to either gastric adenocarcinoma or bronchogenic squamous cell carcinomas.

Introduction

Pulmonary lymphangitic carcinomatosis (PLC) secondary to mucosal head and neck squamous cell carcinoma (HNSCC) is extremely rare, difficult to diagnose in the pre-symptomatic phase, and is rapidly fatal. We aim to increase awareness of this disease entity in the speciality of Head and Neck, as both cases we discuss had unspecific changes noted on pre-treatment staging computed tomography (CT) of the chest that were not further investigated. A literature review of PLC follows a discussion of two recent cases of PLC in our head and neck unit who died of respiratory failure secondary to PLC within 6 weeks of receiving radical treatment with curative intent for HNSCC.

Case reports

Case 1

A 73-year-old man presented with a 2-month history of odynophagia and right neck swelling. He was an ex-smoker who had not consumed alcohol for many years. Staging magnetic resonance imaging (MRI), panendoscopy, and biopsy revealed a T2N2bMx poorly differentiated cancer of the right tonsil. A chest CT (standard protocol 5-mm cuts; Fig. 1 ) showed some small nodules and ground glass opacities. At multidisciplinary review, these were considered likely to be benign changes. No distant metastases were seen.

Fig. 1
Case 1, pre-treatment staging CT.

The patient received intensity modulated radiotherapy at 65 Gy in 30 fractions to the right neck nodal levels 2–4 with concomitant cetuximab 400 mg/m 2 week 1, then 250 mg/m 2 week 2. The cetuximab was stopped due to marked mucosal and cutaneous toxicity and dehydration requiring admission. A radiologically inserted gastrostomy was inserted during radiotherapy to support nutrition. There were no missed fractions of radiotherapy in the radical course.

At outpatient review 6 weeks later the patient reported breathlessness with chest pain and a non-productive cough for 4 weeks unresponsive to oral antibiotics. At review the patient was tachypnoeic, hypoxic, and had a loud second heart sound, widespread wheeze, and crackles. Features of fluid overload were absent. A provisional diagnosis of community-acquired pneumonia prompted admission for oxygen therapy and intravenous broad-spectrum antibiotics. Therapeutic anticoagulation with low molecular weight heparin was administered pending a CT pulmonary angiogram (CTPA).

Admission blood tests showed a normal white blood cell count (WBC) of 9.9 × 10 9 /l (slight neutrophilia 8.2 × 10 9 /l and lymphopaenia 0.5 × 10 9 /l) and a C-reactive protein (CRP) of 67.5 mg/l. Admission arterial blood gases showed a partial pressure of oxygen (pO 2 ) of 7.8 mmHg off oxygen. The electrocardiogram showed sinus tachycardia, left anterior fascicular block, and premature supraventricular beats. D-dimers were not requested. The chest X-ray ( Fig. 2 ) demonstrated widespread nodular shadowing and a pleural effusion.

Fig. 2
Case 1, admission chest X-ray.

A subsequent CTPA (fine cut, 1.5-mm) ( Fig. 3 ) revealed features of lymphangitic carcinomatosis: widespread nodules and extensive miliary shadowing with enlarged nodes that had progressed rapidly. As PLC is not commonly observed in head and neck cancers, a pleural tap for cytology was performed, confirming the presence of a central cluster of poorly differentiated carcinoma cells in a background of reactive mesothelial cells, lymphocytes, and granulocytes ( Fig. 4 ). The patient initially improved with high-dose dexamethasone and oxygen, but unfortunately 10 days later he developed increasingly severe hypoxia and respiratory distress, and with further palliation of symptoms, died that night.

Fig. 3
Case 1, CT pulmonary angiogram: features of lymphangitic carcinomatosis.

Fig. 4
Case 1, cytology of pleural tap.

Case 2

A 65-year-old female who was fit and independent presented with a 6-week history of right-sided odynophagia. She was an ex-smoker and had occasional alcohol intake. She had a past history of oestrogen receptor-positive breast cancer first diagnosed in December 1998. This was treated with breast-conserving surgery, chemotherapy, adjuvant radiotherapy, and tamoxifen. A nodal recurrence 3 years later in the left supraclavicular fossa was treated with radiotherapy and aromatase inhibitors. A further nodal recurrence later that year was treated with chemotherapy, achieving remission. She was on thyroid replacement therapy. Staging MRI and biopsy revealed a T4aN1Mx moderately differentiated carcinoma arising within a field of severe dysplasia on the right retromolar trigone of the mandible. Her staging CT showed numerous suspicious right-sided cervical lymph nodes involving the supraclavicular, submandibular, and internal jugular regions, with no evidence of visceral distant metastases ( Fig. 5 ).

Fig. 5
Case 2, pre-treatment staging CT.

The patient underwent a segmental mandibulectomy, selective neck dissection of the ipsilateral side, tracheostomy, and reconstruction with a composite fibula free flap. Concern during surgery about nodal disease prompted frozen sections of the right supraclavicular nodes, which confirmed the presence of carcinoma. After an overnight stay in the intensive therapy unit (ITU), ventilated and sedated to protect the microvascular anastomosis, she was easily weaned from the ventilator and transferred to the ward on routine thromboprophylaxis. Good progress continued allowing decannulation of the tracheostomy tube on day 7. Histology confirmed a T4aN2bMx moderately differentiated squamous cell carcinoma demonstrating perineural and vascular invasion with clear margins; 58/74 nodes showed tumour, the largest deposit at 25 mm.

Mild dyspnoea and a cough productive of yellow sputum associated with a leukocytosis of 16 × 10 9 /l on days 8–9 prompted a diagnosis of hospital-acquired pneumonia for which she was started on meropenem and teicoplanin. The chest X-ray taken on day 9 is shown in Fig. 6 .

Fig. 6
Case 2, day 9 chest X-ray.

There was no temperature spike. She continued to develop type 1 respiratory failure, and auscultation revealed fine crepitations throughout the lung fields. The cough became unproductive and she had an increasing oxygen requirement unresponsive to chest physiotherapy, nebulized saline, and antibiotics. On day 11, a chest CTPA excluded a pulmonary embolism but showed bilateral pleural effusions and right basal consolidation.

A chest drain was inserted the following day and removed 24 h later. She had a Mycoplasma false-positive titre of 320, but repeat testing the following day showed a result of <20. Signs of exhaustion prompted transfer back to the ITU on day 15. Her ITU admission arterial blood gases were pO 2 7.05 mmHg, pCO 2 5.96 mmHg, pH 7.45, base excess 7.3 mmol/l, HCO 3 30.8 mequiv./l, and lactate 1.0 mmol/l on FiO 2 60%. Her ITU admission inflammatory markers were CRP 251 mg/l and WBC 22.39 × 10 9 /l. A chest CT taken on day 15 is shown in Fig. 7 . Cytology from the pleural taps showed atypia consistent with florid reactive changes for which later immunohistochemistry failed to prove malignancy. She was maintained on non-invasive ventilation for a week, but on day 19 she was tiring and was intubated and ventilated, and noradrenaline was started. A bronchoscopy was unremarkable, and washings showed acute inflammation with atypia, probable reactive changes only, and no proof of malignancy. A high-resolution chest CT (HRCT) on day 21 showed extensive bilateral consolidation and a large right pleural effusion, representing extensive inflammation and possible contribution of acute respiratory distress syndrome (ARDS) ( Fig. 8 ).

Fig. 7
Case 2, day 15 chest CT.

Fig. 8
Case 2, day 21 high-resolution CT of the chest.

On day 26 she was transferred to an outlying ITU to receive extracorporeal membrane oxygenation (ECMO) treatment. An admission chest CT showed extensive ground glass consolidation in the lungs and pleural collections compatible with ARDS, but no evidence of malignancy. On day 35, the problems were ARDS, inotrope dependence, hypercalcaemia, hypernatraemia, and flaccid quadriparesis secondary to neuropathy. On day 36 she had a pulmonary haemorrhage with resultant asystolic cardiac arrest unresponsive to cardiopulmonary resuscitation.

The hospital post-mortem described macroscopically heavy, solid lungs, densely adherent to the chest wall, the surfaces of which were covered in small white plaques up to 4 mm in diameter. The bronchi and parenchyma were unobstructed and no pulmonary arterial thromboemboli were seen. Microscopically the lungs showed widespread, insidious infiltration by squamous cell carcinoma associated with marked lung fibrosis, also noted at the pleural margins. There was also extensive lymphangitic carcinomatosis and tumour plugs in the larger blood vessels associated with thrombosis. There were squamous cell carcinoma deposits in the spleen and adrenals. There was no evidence of adenocarcinoma.

Case reports

Case 1

A 73-year-old man presented with a 2-month history of odynophagia and right neck swelling. He was an ex-smoker who had not consumed alcohol for many years. Staging magnetic resonance imaging (MRI), panendoscopy, and biopsy revealed a T2N2bMx poorly differentiated cancer of the right tonsil. A chest CT (standard protocol 5-mm cuts; Fig. 1 ) showed some small nodules and ground glass opacities. At multidisciplinary review, these were considered likely to be benign changes. No distant metastases were seen.

Fig. 1
Case 1, pre-treatment staging CT.

The patient received intensity modulated radiotherapy at 65 Gy in 30 fractions to the right neck nodal levels 2–4 with concomitant cetuximab 400 mg/m 2 week 1, then 250 mg/m 2 week 2. The cetuximab was stopped due to marked mucosal and cutaneous toxicity and dehydration requiring admission. A radiologically inserted gastrostomy was inserted during radiotherapy to support nutrition. There were no missed fractions of radiotherapy in the radical course.

At outpatient review 6 weeks later the patient reported breathlessness with chest pain and a non-productive cough for 4 weeks unresponsive to oral antibiotics. At review the patient was tachypnoeic, hypoxic, and had a loud second heart sound, widespread wheeze, and crackles. Features of fluid overload were absent. A provisional diagnosis of community-acquired pneumonia prompted admission for oxygen therapy and intravenous broad-spectrum antibiotics. Therapeutic anticoagulation with low molecular weight heparin was administered pending a CT pulmonary angiogram (CTPA).

Admission blood tests showed a normal white blood cell count (WBC) of 9.9 × 10 9 /l (slight neutrophilia 8.2 × 10 9 /l and lymphopaenia 0.5 × 10 9 /l) and a C-reactive protein (CRP) of 67.5 mg/l. Admission arterial blood gases showed a partial pressure of oxygen (pO 2 ) of 7.8 mmHg off oxygen. The electrocardiogram showed sinus tachycardia, left anterior fascicular block, and premature supraventricular beats. D-dimers were not requested. The chest X-ray ( Fig. 2 ) demonstrated widespread nodular shadowing and a pleural effusion.

Jan 19, 2018 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Pulmonary lymphangitic carcinomatosis from head and neck squamous cell carcinoma
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