Hepatic diffuse intra-sinusoidal metastases of pulmonary small-cell carcinoma

P Vaideeswar¹, S Munot¹, A Rojekar¹, K Deodhar²,  
¹ Department of Pathology (Cardiovascular and Thoracic Division), Seth GS Medical College, Mumbai, Maharashtra, India
² Department of Pathology (Cardiovascular and Thoracic Division), Tata Memorial Hospital, Mumbai, Maharashtra, India

Correspondence Address:
P Vaideeswar
Department of Pathology (Cardiovascular and Thoracic Division), Seth GS Medical College, Mumbai, Maharashtra
India

Full Text

Sir,

Small-cell carcinoma of the lung (SCLC) is well known for its aggressive behavior with rapid growth, early metastases and an association with para-neoplastic syndromes. Liver is a common site for SCLC metastases, usually manifesting as multifocal nodularity and often devoid of clinically evident hepatic dysfunction. On rare occasions, malignant cells of SCLC diffusely infiltrate the hepatic sinusoids to produce acute hepatic failure (AHF), [1] a feature in this reported case.

A 69-year-old man, chronic alcoholic and smoker, was brought to the casualty for a sudden-onset altered sensorium since morning; there was no history of an alcoholic binge or head injury. On questioning the relatives, it was found that the patient additionally had exertional dyspnea, episodic chest pain, cough and streaky hemoptysis for a month. On examination, he was afebrile with normal pulse rate, blood pressure of 180/80 mm Hg, mild icterus and bilateral rhonchi. He was mechanically ventilated but succumbed within an hour of admission.

At autopsy, significant findings were present in the liver, lungs, heart and brain. The liver was moderately enlarged (1.4 kg), had rounded borders with pale yellow to focally congested cut surface [Figure 1]a. On histology, the sinusoids were dilated to accommodate singly dispersed or balls of small epithelial cells [Figure 2]a. They had scanty cytoplasm and dark blue hyperchromatic nuclei. Immunohistochemistry revealed positivity for synaptophysin and CD 56 [[Figure 2]a, inset]. Some sinusoids also showed immature hemopoietic precursors including megakaryocytes [Figure 2]b. These features suggested sinusoidal infiltration of small-cell carcinoma with myeloid metaplasia in the liver. The primary tumor was seen as a firm, fleshy, irregular mass, 4×4×3cm, in the posterior segmental bronchus of the right upper lobe [Figure 1]b. Other findings included intracranial hemorrhage (subdural hematoma, patchy subarachnoid hemorrhage, multifocal hemorrhages in both cerebral hemispheres and mid-brain) with raised intracranial pressure, healed myocardial infarction, hilar lymph nodal/bone marrow metastases.{Figure 1}{Figure 2}

AHF or fulminant hepatic failure is an unusual disorder manifesting with jaundice, coagulopathy and/or multi-organ dysfunction. It is defined as hepatic encephalopathy developing within eight weeks of the onset of such symptoms in a patient without previous hepatic disease and generally caused by viral hepatitis and drug-induced injury. [2] Diffuse intrasinusoidal metastasis of malignancy (DIM) is an unusual cause, and in a large clinical series accounted for 0.44% of AHF cases. [3] Though hematologic malignancies are commonly implicated, DIM can also occur with carcinomas originating in several organs, [4] including the lungs; the first reported cases in 1955, [5] were bronchogenic carcinomas. About 30 cases of DIM in SCLC have been reported. [1],[4],[6],[7] The patients present with a wide range of biochemical alterations (raised levels of bilirubin, transaminases, alkaline phosphatase, lactate dehydrogenase, uric acid, ammonia and prothrombin time), occurring from hepatocytic atrophy or necroses induced by mechanical obstruction, hypoxia or cytokine release. [7] Our patient, who was icteric with evidence of coagulopathy, was not thoroughly investigated. The DIM had produced moderate hepatomegaly and it is important to note that, paradoxically, the enlarged liver has negative imaging findings. [7] The hepatic sinusoids also revealed hemopoietic precursors (myeloid metaplasia, not documented in the other reports of DIM) as a reaction to bone marrow involvement. Further, the precursors, through the release of cytokines, may add to the hepatic dysfunction. [7] This pattern of metastasis had been diagnosed at autopsy, as have been the others, and hence a liver biopsy is indicated early in the course of a patient with AHF and hepatomegaly, devoid of viral or drug-induced injury.

References