Mediastinal Primitive Neuroectodermal Tumour ( PNET ) – A Rare Case of Horner ’ s Syndrome

Primitive neuroectodermal tumour (PNET) is a rare mediastinal tumour which may infiltrate pulmonary parenchyma and chest wall. Histopathologically, it is a round cell tumour, and on immunohistochemistry, tumour cells express for CD-99 (MIC-2). Here we report a rare case of PNET presented as unresectable mediastinal tumour with chest wall infiltration, superior vena caval obstruction and Horner’s syndrome in an adolescent female. Keyword: Primitive neuroectodermal tumour (PNET), Mediastinal tumour, Horner’s syndrome, Superior vena caval onbstruction, Round cell tumour, CD – 99. 1. Assistant Professor, Department of Pulmonary Medicine, Medical College, Kolkata. 2. Professor& H.O.D, Pulmonary Medicine, Medical College, Kolkata. 3. MD (TB & Respiratory Medicine); Assistant Professor, Department of Pulmonary Medicine, Medical College, Kolkata. 4. RMO–cum–Clinical Tutor, Department of Pulmonary Medicine, Medical College, Kolkata. 5. Professor, Department of Pulmonary Medicine, Calcutta National Medical College, Kolkata. 6. Professor& HOD, Pathology, Midnapore Medical College, Midnapore. Correspondence: Anirban Das, Address: C/o Mr Pradip Das Peon Para, Bhatchala, P.O: Sripalli, Dist.: Burdwan, West Bengal, India, Pin: 713 103. E-mail: dranirbandas_chest@ rediffmail.com; Mob. : (0)9434672168 congestion were present. She also complained of frontal headache, difficulty in swelling, hoarseness of voice, but no visual disturbance, nausea, vomiting, convulsion, altered level of consciousness, hemoptysis or fever. History of loss of weight & appetite was present. She was normotensive and non – diabetic. No addiction history was given. Her menstrual history was within normal limit. On general survey, pallor was present, but no cyanosis, clubbing and palpable lymph node. Neck vein was engorged, non – pulsatile, and abdomino – jugular reflux was absent. Her pulse rate was 96 beats / minute, respiratory rate, 24 breaths / minute and blood pressure, 124/80 mmHg. There was swelling of face, neck, upper part of the chest and upper limbs. Examination of eye revealed partial ptosis, miosis, enophthalmos, ipsilateral facial anhydrosis and loss of ciliospinal reflex on right side, i.e., Horner’s syndrome was present. On examination of respiratory system, a right sided, irregular, hard, tender swelling of 4 cm x 5 cm in size over infraclavicular area with supraclavicular extension was revealed. It was fixed to underlying bony structure and overlying skin was also fixed, surface of the swelling was irregular. Direction of blood flow in engorged, tortuous veins over the chest wall was above downwards. Trachea was shifted towards left, and apex beat was in 5th intercostal space, 1⁄2 inch medial to left midclavicular line. Vocal fremitus was diminished over infraclavicular, mammary, and inframammary areas on right side. Percussion note was dull J MEDICINE 2012; 13 : 85-87

congestion were present.She also complained of frontal headache, difficulty in swelling, hoarseness of voice, but no visual disturbance, nausea, vomiting, convulsion, altered level of consciousness, hemoptysis or fever.History of loss of weight & appetite was present.She was normotensive and non -diabetic.No addiction history was given.Her menstrual history was within normal limit.
On general survey, pallor was present, but no cyanosis, clubbing and palpable lymph node.Neck vein was engorged, non -pulsatile, and abdomino -jugular reflux was absent.Her pulse rate was 96 beats / minute, respiratory rate, 24 breaths / minute and blood pressure, 124/80 mmHg.There was swelling of face, neck, upper part of the chest and upper limbs.Examination of eye revealed partial ptosis, miosis, enophthalmos, ipsilateral facial anhydrosis and loss of ciliospinal reflex on right side, i.e., Horner's syndrome was present.On examination of respiratory system, a right sided, irregular, hard, tender swelling of 4 cm x 5 cm in size over infraclavicular area with supraclavicular extension was revealed.It was fixed to underlying bony structure and overlying skin was also fixed, surface of the swelling was irregular.Direction of blood flow in engorged, tortuous veins over the chest wall was above downwards.Trachea was shifted towards left, and apex beat was in 5th intercostal space, ½ inch medial to left midclavicular line.Vocal fremitus was diminished over infraclavicular, mammary, and inframammary areas on right side.Percussion note was dull   chromogranin A, TdT and CD -45.Serum LDH, α-HCG and α-fetoprotein were within normal limit.USG of whole abdomen and contrast enhanced CT scan of brain revealed no abnormality.Hence our diagnosis was primitive neuroectodermal tumour (PNET) presenting as mediastinal mass lesion infiltrating right lung and anterior chest wall, complicated by superior vena caval obstruction and Horner's syndrome on right side.After exclusion of metastasis by extensive clinical examination and investigations, the patient was advised for cytotoxic chemotherapy, which was combined regimen of cyclophosphamide, vincristine and doxorubicin.But unfortunately, tumour was so aggressive that, the patient died before starting the regimen.

Discussion:
PNET is a rare (1.8 % of all mediastinal tumours), undifferentiated soft tissue sarcoma which is highly malignant tumour. 3It is believed that it arises from embryonal cells migrating from the neural crest. 4Ewing's sarcoma and PNET are different morphological expressions of a single neoplastic entity and have unique chromosomal translocation, t(11;22)(q24;q12). 1 PNET is most commonly seen in young females, especially in second decade of life.Kushner et al reported 54 patients with this disease in 1990 and incidence of affected sites was as follows : chest wall (33.3%), pelvis (22.2%), paraspinal region (13.0%),retroperitoneum (11.1%), limbs (9.3%), abdomen (7.4%), neck (1.9%), and unknown site (1.9%). 5Similar result was reported by Kennedy et al in 2000. 6oracic involvement of PNET is characteristically painful, invasive thoracic tumours that may develop on and invade the chest wall, lung, or mediastinum.It is soft, fleshy, whitish or yellowish tumour with areas of hemorrhage and necrosis.Mediastinal mass lesion may result in superior vena caval obstruction, hoarseness of voice due to left recurrent laryngeal nerve palsy, Horner's syndrome due to involvement of cervical sympathetic trunk above the stellate ganglion, dysphagia due to esophageal compression and C 8 & T 1 radiculopathy, when tumour extension occurs to pulmonary apex.Sites of metastases of PNET are lung, regional lymph nodes, bone, bone marrow.Histopathology of thoracopulmonary PNET is characterized by presence of monotonous sheets of small round cells with occasional rosettes formation like, Homer -Wright pseudorosette (central solid core of neurofibrillary material) and Flexner -Wintersteiner pseudorosette (central lumen or vesicle).But histopathology alone can't confirm the diagnosis; hence immunohistochemistry is essential to establish the diagnosis.Tumour cells of thoracopulmonary PNET are CD99 positive but cytokeratin negative.CD99 positivity has 95% sensitivity for PNET. 7In our case, the female patient presented in her second decade of life, with unresectable disease.Chest wall extension of her mediastinal lesion resulted in painful chest wall swelling, besides the superior vena caval obstruction, hoarseness of voice, dysphagia and Horner's syndrome which were due to mediastinal mass effect.She showed typical histopathological and immunohistochemical features of PNET.
Classically, thoracopulmonary PNET is a highly aggressive neoplasm with a mean survival of eight months. 4Prognosis is still poor despite multidisciplinary modalities of treatment which includes excision, localized radiotherapy and systemic chemotherapy (cyclophosphamide, vincristine, doxorubicin) 8 , with a 2 year survival of 38% and a 6 year survival of 14%. 3 But in case of localized disease, 5 -year survival rate of 60% has been described. 9

J
MEDICINE 2012; 13 : 85-87 .from 2nd intercostal space downwards along right midclavicular line, and also over apex, accompanied by percussion tenderness.Sternal percussion was dull.Diminished vesicular breath sound was audible over infraclavicular, mammary, and infrascapular areas on right side.No adventitious sound was audible and vocal resonance was diminished over corresponding areas where vocal fremitus was diminished.No ascites, hepatomegaly and lymphadenopathy were revealed on examination of abdomen.Examination of other systems revealed no abnormality.Complete haemogram and blood biochemistry were within normal limit.Sputum for acid fast bacilli and malignant cell was negative.Chest X-ray P.A. view revealed a mass lesion occupying almost whole right hemiothorax with sparing the right costophrenic angle and erosion of postero -lateral part of right second rib.Medial border of the lesion was merged with mediastinum.(Fig.-1) Contrast enhanced CT scan of thorax showed right sided mass lesion originating

Fig.- 1 :
Fig.-1: Chest X -ray P.A. view showing right lung mass with sparing the right costophrenic angle and erosion of postero -lateral part of right second rib