malignant melanoma is an aggressive skin cancer accounting for about 4.5% of all new cancer cases and 1.7% of all cancer deaths in the united states .
malignant melanoma can metastasize to various sites including , but not limited to , the brain , lung , and gastrointestinal tract .
intra - thoracic metastases in malignant melanoma most commonly present as multiple or solitary pulmonary nodules and rarely as isolated pleural effusions .
though there are few reported cases of recurrent malignant melanoma presenting with isolated pleural effusion , what makes our case intriguing , is its presentation in the context of coexisting chronic lymphocytic leukemia ( cll ) .
a 65-year - old caucasian woman presented in march 2007 with a 3-month history of painless left - sided cervical lymphadenopathy .
she denied any associated fevers , chills , loss of weight , dyspnea , dysphagia , or any other symptoms .
the patient 's surgical history was pertinent for a completely resected stage ia melanoma over the left shoulder 16 years before this presentation .
physical exam revealed enlarged and non - tender cervical and axillary lymph nodes without splenomegaly .
a complete blood picture showed a white blood cell count of 14.7  103/l , an absolute lymphocyte count of 7.35  103/l , hemoglobin of 13.8 g / dl , a platelet count of 258  103/l , and lactate dehydrogenase of 291 u / l .
flow cytometry of the peripheral blood demonstrated a monoclonal lymphocyte population expressing cd5 , cd19 , cd20 , cd24 , cd43 , and cd52 with lambda light chain restriction and no increase in cd34-positive blasts .
based on the above findings , the patient was diagnosed with rai stage i cll and placed under observation .
two years after her initial diagnosis , the patient presented with progressive dyspnea , associated with pleuritic chest pain and a 20 lbs weight loss over a period of 3 months .
physical examination revealed increased axillary and cervical lymphadenopathy and decreased breath sounds over the right lung .
white blood cell count was noted to be 53.4  103/l , and she had an absolute lymphocyte count of 40.7  103/l .
the pleural fluid analysis was consistent with an exudative effusion , with increased atypical lymphocytes .
the majority of the lymphocytes were cd4 + t - lymphocytes ( cd4:cd8 in a ratio of 15 : 1 ) , but polymerase chain reaction failed to show any clonal t - cell receptor- or t - cell receptor- gene rearrangements .
secondary to rapid reaccumulation of pleural fluid , increasing lymphadenopathy , and rapid doubling time of lymphocyte count , the decision to treat symptomatic cll was made .
chemotherapy with pentostatin , cyclophosphamide , and rituximab did not result in any meaningful clinical response .
as the patient 's pleural effusion was refractory to cll treatment , video - assisted thoracoscopic surgery was performed , which demonstrated diffuse nodular thickening of both visceral and parietal layers of the pleura ( fig .
a biopsy of these lesions revealed enlarged cells with an increased nuclear - cytoplasmic ratio and pleomorphic nuclei with occasional cherry red nucleoli ( fig .
electron microscopy revealed type ii melanosomes with cross - striated lattice in an enclosed membrane ( fig .
1e ) , type iii melanosomes with increased deposition of electron - dense melanin , and type iv melanosomes with highly electron - dense melanin ( fig .
computed tomography of the chest revealed extensive lobulated tumor lining the entirety of the right parietal pleural surface without any evidence of parenchymal involvement .
the patient 's medical condition rapidly declined , and she ultimately succumbed to death before initiation of any therapy .
cll is a low - grade lymphoproliferative state characterized by the accumulation of functionally incompetent monoclonal b - lymphocytes .
immunosuppression in cll is hypothesized to be a result of immunosuppressive factors released by the neoplastic b cells that downregulate t - cell function .
loss of  chain and costimulatory molecule cd28 on t - cell lymphocytes   along with reduced il-4 and ifn- expression by cd4 + t cells in patients with cll   also seem to play a role in the t - cell dysfunction in cll .
the immune system plays a crucial role in immunosurveillance against malignant transformation and tumor propagation   and , hence , t - cell dysregulation and dysfunction in cll patients increase their risk of recurrent or secondary malignancies . in several retrospective studies involving patients with cll ,
increased incidence of secondary cancers like kaposi sarcoma , head and neck cancer , lung cancer , and malignant melanoma was noted [ 7 , 8 ] .
reported that the overall risk of any second - incident cancer in cll patients was higher than in the general population ( second - incident cancer : 2.17 , 95% ci 2.072.27 ) , and the risk of melanoma was found to be 7.74 times that of the general population ( 95% ci 6.858.72 ) .
hence , prompt detection and treatment of the malignant melanoma are crucial in patients with cll .
metastases to various viscera have been known to occur even after the resection of the original tumor . however , isolated pleural metastasis with pleural effusion as a metastatic recurrence is very rare . in a series of 130 patients with malignant melanoma and thoracic complications ,
15% were found to have pleural effusions , and less than 3% had isolated and unilateral pleural effusion .
only a handful of cases with recurrent isolated metastatic pleural involvement presenting after a prolonged period after resection of the primary lesion were reported , with the longest reported progression - free survival being 14 years [ 12 , 13 ] . in our patient , isolated pleural metastases were noted 16 years from the complete resection of the skin lesion . computed tomography of the chest may aid in the diagnosis of pleural metastasis by demonstrating thickened pleura and parenchymal involvement .
positron emission tomography may also aid in the detection of fdg - avid pleural metastasis .
thoracentesis , unless contraindicated , should be considered in all cases of suspected malignant pleural effusions .
effusions in malignant melanoma are relatively richer in cd8 + than in cd4 + t - lymphocytes . in our case , the majority of the cells in the pleural effusion expressed cd4 + , and only 12% of the lymphocytes expressed the markers expressed by tumor cells .
the latter can be explained by the deficient migratory capacity of the b - cll cells , which might have led to a relative enrichment of reactive t cells .
video - assisted thoracoscopic surgery and pleural biopsy may be useful for diagnosis and to perform molecular studies .
concomitant history of cll , pleural fluid studies suggestive of cll , and a distant history of malignant melanoma made the diagnosis challenging in our patient .
we speculate that immune dysregulation associated with cll could have led to recurrence of melanoma in our case .
our case underlines the importance of having a suspicion for malignant melanoma in patients presenting with isolated pleural effusion , especially in the setting of an underlying lymphoproliferative disorder and a previous history of melanoma .
 isolated pleural metastasis with pleural effusion is a rare occurrence in malignant melanoma . 
 we report an unusual case of a patient with chronic lymphocytic leukemia ( cll ) and recurrent pleural effusions . 
 the pleural fluid cytology and immunohistochemistry profile were consistent with the diagnosis of cll . however 
 , chemotherapy with pentostatin , cyclophosphamide , and rituximab did not result in any meaningful clinical response . 
 a video - assisted thoracoscopic surgery and biopsy of the affected nodular parietal layer of the pleura were consistent with malignant melanoma . 
 our case underlines the importance of having a suspicion for secondary causes of effusion in patients with cll . 
 we briefly discuss the mechanisms of an increased incidence of secondary cancers in cll and the diagnosis of isolated pleural metastases in malignant melanoma . 