Alveolar cell carcinoma of the lung with osteoblastic metastases in the spine.
Amongst the malignancies of lung, alveolar cell carcinoma is perhaps the least common and not so well described in the literature. It is known to result in widespread metastases, but specific osteoblastic metastases have not been described.
The purpose of presenting this paper is to describe a rare case of osteoblastic metastases in alveolar cell carcinoma.
Mrs. C. S., a 50 year old housewife, was admitted to the King Edward VII Memorial Hospital, Bombay, with history of paraplegia for a period of one month. Patient was apparently well two months prior to admission, when she developed mild cough with small quantity of greenish yellow expectoration and progressive weakness. She had noticed severe pain in both lower limbs and left hip about a month ago. This was maximum on movements of the hip joint and she was unable to walk for 2 weeks prior to admission. There was no history of trauma or fever. There were no symptoms related to cranial nerves or upper limbs. Patient could not give details of bladder and bowel symptoms but said that she had `difficulty' in passing urine. There was no history of retention of urine. There was no history of haemoptysis or tuberculosis. She did not have any symptoms related to gastro intestinal system. She was menopausal and did not have any bleeding or discharge per vaginum. There was no history of having noticed any lump in the breast or any bloody discharge from the nipples.
Examination revealed an averagely built and poorly nourished female. She was febrile and pale. There was no clubbing of nails. Her pulse was 100/min. and blood pressure was 100/ 70 mm of Hg. There was no significant lymphadenopathy. Her central nervous system examination revealed normal higher functions and cranial nerves. Her upper limbs did not show any abnormal findings.
In the lower limbs, she had flaccid paraparesis with extremely painful and weak movements especially at the left hip joint. She had wasting of quadriceps and calf muscles on both sides. She had a fixed flexion deformity at the left hip (40° flexion) and knee (40° flexion). There was no ataxia in the upper limbs and it was difficult to judge the same in the lower limbs. Patient was extremely uncooperative for sensory system examination, but appeared to have saddle anaesthesia and loss of position and vibration sense in lower limbs upto the anterior superior illiac spine. Her deep tendon jerks were normal in the upper limbs and absent in the lower limbs. Her plantar responses could not be elicited and abdominal reflexes were lost. The anal sphincter was lax.
Her skull was normal but there was extreme tenderness over L2-L3-L4 spines and all over the sacrum, Her `SLR test' was positive at 30° on the right side. There were no other bony swellings felt anywhere. Her respiratory system revealed bilateral coarse crepitations all over the lung fields without any other localising signs. Her alimentary system did not reveal any abnormal finding. Her liver was not palpable. Her thyroid was not enlarged and there was no bruit over it. Her breasts did not show any lump. Her `per vaginum' examination done by a gynaecologist was normal. Orthopaedic surgeons had ruled out any local hip pathology.
Her investigations revealed the haemoglobin to be 10.4 gm%, WBC-9600 cells/cmm. with a differential count of P-64%, L-35% and E-1%. Her ESR at the end of 1 hour was 88 mm. Her urine examination revealed a trace of albumin and a few pus cells. Her postprandial blood sugar was 110 mg%, BUN was 18.5 mg% and serum creatinine was 1.1 mg%. Her serum electrolytes revealed Sodium to be 142 mEq/1., Potassium, 3.5 mEq/1., and Chloride, 95 mEq/1.
Her serum proteins were 6 gm%, albumin2.9 gm% globulin-3.1 gm%. Serum total bilirubin was 0.7 mg% SGOT-15 Units and SGPT -20 units. Her Serum Calcium was 9.5 mg%, phosphorus, 5 mg% and alkaline phosphatase -20 KA units. Her electrocardiogram was within normal limits. Her X-Rays of the skull, spine, hip-joint and chest are as shown in [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]. They were suggestive of osteoblastic metastases in the spine, sacrum and skull. Her X-Ray chest was suggestive of multiple miliary deposits, probably secondaries with patchy areas of consolidation.
A provisional diagnosis of a compressive paraplegia due to secondary deposits in the spine was considered. In this female patient the secondary deposits being osteoblastic, carcinoma of breasts, thyroid, stomach, bronchus, carcinoid tumor, renal carcinoma, Hodgkin's disease were considered as possible primary tumours. However, available clinical findings and investigations did not support any of these. The patient was treated with antibiotics and intravenous fluids. However, before any further investigations could be carried out, she succumbed on the 3rd day of hospitalisation, due to cardiorespiratory arrest.
Her postmortem examination revealed the following positive findings.
Brain and meninges were normal.
Terminal portion of the spinal cord and the nerve roots did not show any compression or haemorrhages externally. On histology, the spinal cord at that level showed central chromatolysis of the anterior horn cells. White matter showed spongy degeneration suggestive of compression myelopathy. There were no malignant changes. Vertebral bodies (L1 to L5) and the sacrum were very friable and showed evidence of metastasis on cut section. Lungs were congested. On cut section the lower lobes of both the lungs showed dark red friable areas with small abscesses. Hilar and tracheobronchial lymph nodes were normal. Autopsy diagnosis of broncho pneumonia was made. However, the lung histology revealed alveoli filled with faintly stained mucinous material and clusters of tall columinar cells lining the alveoli suggestive of alveolar cell carcinoma [Fig. 6]. These malignant cells were tall columnar with basal nuclei, and appeared to line the alveoli all over. Mucous glands of the larger bronchi also showed similar changes. This was highly suggestive of adenocarcinoma of alveolar cell type. Hilar and tracheobronchial lymph nodes, liver and spleen were normal and did not show any metastases. Kidneys showed solitary metastasis in each, with similar histological pattern to that of lung. A histological diagnosis of "alveolar cell carcinoma (adenocarcinoma) with metastases in the bones and kidneys with compressive myelopathy was made.
Alveolar cell carcinoma is a malignant tumour arising from the alveolar epithelium. It is fascinating in that, its origin, terminology, relation to previous lung injury and many other concepts remain unsolved.
It. comprises of about 1-2% of total malignant tumours of the lung, though due to better diagnostic facilities, its incidence has been claimed to have increased. It is common in females especially the solitary type of lesion5 though some authors report it to have equal incidence in both the sexes. It clearly differs from the common bronchogenic carcinoma in that unlike the latter, there is no relation between smoking and alveolar cell carcinoma. It rarely invades the primary bronchi, unlike the cases of bronchogenic carcinoma though a rare case of primary bronchial spread, and hence a bronchoscopically diagnosed case of alveolar cell carcinoma has been reported.
The controversy over the carcinogenetic potentials of old inflammatory and fibrotic lesions, leading to alveolar cell carcinoma is still not settled. It appears that, as against the previous beliefs of multicentric origin of alveolar cell carcinoma, more and more evidence points towards a unicentric origin of the tumour. Some authors, believe that the tumour consists of two types (a) solitary nodular variety and (b) a diffuse variety. Though both have identical histological appearances. the clinical and prognostic features of the two types vary and there may be histochemical differences in these two groups. Those cases of solitary shadows in the chest on X-Ray, have either no symptoms or minimal symptoms and have good prognosis. A complete cure rate without any recurrence is seen in almost 60-70%. The patients with diffuse pulmonary involvement have copious sputum. Signs and symptoms of restrictive airway disease and the radiological picture may vary from diffuse in filtrative changes to patchy consolidation, cavitation and metastatic pleural effusion, hilar enlargement etc. The prognosis of this group is rather poor, and in one series all the cases who underwent resection surgery, developed recurrences and metastatic foci.
The interesting aspect of this case is the old manifestation of osteoblastic metastases and paraparesis due to compressive myelopathy as shown at the autopsy. Though metastases in these cases are frequent and are found in various organs, to the best of our knowledge, osteoblastic metastases have not been described in the literature. Watson and Farpour  describe 82 cases studied at autopsy (out of 265 cases of alveolar cell carcinoma studied by them) in which metastases to opposite lung, brain and adrenals were the commonest. Renal, hepatic, cardiac and pleural metastases were seen in a few of their cases, but no report of osseous metastases could be found. Marcq and Galy report 4 cases of cerebral and osseous metastases in their report, however details of these osseous metastases (whether osteolytic or osteoblastic) are not mentioned. The common bronchogenic carcinoma produces osteolytic metastasis, though rarely it can produce osteoblastic metastasis. In this respect the present case was unique in its presentations.
It is also important to realise that both the radiological findings and the gross autopsy diagnosis may be that of "bronchopneumonia" or "secondary metastases", in a case of alveolar cell carcinoma as it happened in the case described. One must consider a possibility of alveolar cell carcinoma in all such cases.
We express our sincere thanks to the Dean, K.E.M. Hospital for allowing us to publish this case. We also thank the Department of Pathology and Dr. (Smt.) Suman G. Kinare, Professor and Head of the Department of Pathology for her kind help in the histological study of this case.