Cytology of metastatic renal medullary carcinoma in pleural effusion: A study of two cases

Renal medullary carcinoma (RMC) is a rare and aggressive malignant epithelial neoplasm of the kidney. It almost exclusively affects children and young adults with a sickle cell trait or sickle cell disease. The majority of RMC patients present with widely disseminated disease at the time of diagnosis. Herein, we report two cases of young African‐American patients with history of sickle cell trait, hematuria and renal mass, who present with malignant right pleural effusions. The cytology of pleural effusion reveals predominantly clusters and individual tumor cells. The tumor cells show high nuclear to cytoplasmic (NC) ratios and large nuclei with nuclear pleomorphism, nuclear grooves, and prominent single or multiple nucleoli. The cytoplasm is dense with a vacuolated and two‐tone appearance. Surgical specimens of renal mass and lymph node show features of RMC. Metastatic RMC to the serous cavity is rare and may present a diagnostic dilemma since it may mimic a poorly differentiated adenocarcinoma or other high‐grade malignant neoplasms. RMC should be considered in the differential diagnosis in young patients with a renal mass, particularly in those with history of sickle cell trait or sickle cell disease. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Renal medullary carcinoma: a report of 2 cases and review of the literature

Renal medullary carcinoma is a recently described aggressive neoplasm of the kidney. With the exception of 2 patients, all other reported cases have been associated with sickle cell hemoglobinopathies, mainly sickle cell trait and hemoglobin SC disease. Renal medullary carcinoma is a highly malignant tumor with evidence of angiolymphatic and distant metastasis at the time of diagnosis. No specific genetic abnormality has been identified in this neoplasm despite its close association with a genetic disease. We describe 2 cases of renal medullary carcinoma, one associated with hemoglobin SC disease, and the other with what we believe to be the first reported case associated with sickle cell disease.     

Bone marrow necrosis in antiphospholipid syndrome.

Bone marrow necrosis (BMN) is a relatively rare entity and has been associated with a poor prognosis. It is most commonly found in patients with neoplastic disorders, severe infections and sickle cell anemia. An unusual case of antiphospholipid syndrome (APS) with extensive bone marrow necrosis is described in a 27 year old woman. The patient presented with severe pancytopenia, some cognitive impairment resulting from a previous cerebrovascular accident, fever, hypertension, dyspnoea, tachycardia, hepatosplenomegaly, and vaginal bleeding. Her laboratory findings included a strongly positive Coombs' test (anti-IgG and anti-C3d), a prothrombin time of 23 seconds and an activated partial thromboplastin time of 45 seconds. Anticardiolipin antibody tests were positive. Antinuclear and anti-DNA antibodies were negative but the anti-SM test was positive. A bone marrow biopsy specimen was reported as showing extensive necrosis. The patient was treated with steroids, transfusion, and plasma exchange with some clinical improvement but her pancytopenia did not respond and necessitated frequent transfusions. This case lends further support to the association between APS and BMN.     

Sickle Cell Trait: An Update

A review of the literature on sickle cell trait was completed by Sears in 1978. Since that time, several papers have been published concerning the possible health risks of sickle cell trait. Data presented from these studies show that there is no association with sickle cell trait and overall survival, overall mortality, overall morbidity, frequency and length of hospitalization, short-term survival of renal transplant recipient, and inheritance of glucose-6-phosphate dehydrogenase. Association with sickle cell trait is very likely in the following: splenic infarction at high altitudes (over 10,000 feet), in unpressurized airplane flight and mountain climbing, bacteriuria and pyelonephritis in pregnancy, hyposthenuria, hematuria, and delayed resolution of anterior chamber hyphema. Although these conditions have a statistical significant association with sickle cell trait, they occur quite infrequently. Thus, when they are observed, other causes should be sought before attributing them to sickle cell trait. Reduced mortality from Plasmodium falciparum infection also shows significant association with sickle cell trait.     

Bone marrow necrosis. Report of a case and a brief review of the literature

Bone marrow necrosis (BMN) is a rare finding in specimens from living patients. It is most commonly found in patients with neoplastic disorders, severe infections and sickle cell disease. We present a patient with Hodgkin's disease who developed extensive BMN 11 months before death. A concise review of the literature is also presented.     

Renal medullary carcinoma: report of seven cases from Brazil.

We report seven cases of renal medullary carcinoma collected from several institutions in Brazil. In spite of a relatively high incidence of sickle cell trait in Brazil, this is a rare tumor. All patients were males between the ages of 8 and 69 years (mean 22 years). From the collected information, the most frequent presenting symptoms were gross hematuria and flank or abdominal pain. The duration of symptoms ranged from 1 week to 5 months. Most of the tumors were poorly circumscribed arising centrally in the renal medulla. Size ranged from 4 to 12 cm (mean 7 cm) and hemorrhage and necrosis were common findings. All seven cases described showed sickled red blood cells in the tissue and six patients were confirmed to have sickle cell trait. All cases disclosed the characteristic reticular pattern consisting of tumor cell aggregates forming spaces of varied size, reminiscent of yolk sac testicular tumors of reticular type. Other findings included microcystic, tubular, trabecular, solid and adenoid-cystic patterns, rhabdoid-like cells and stromal desmoplasia. A peculiar feature was suppurative necrosis typically resembling microabscesses within epithelial aggregates. The medullary carcinoma of the 69-year-old patient was associated with a conventional clear cell carcinoma. To our knowledge, this association has not been previously reported and the patient is the oldest in the literature. The survival after diagnosis or admission ranged from 4 days to 9 months. The 8-year-old African-Brazilian patient with a circumscribed mass is alive and free of recurrence 8 years after diagnosis. This case raises the question whether a periodic search for renal medullary carcinoma in young patients who have known abnormalities of the hemoglobin gene and hematuria could result in an early diagnosis and a better survival.     

Intragraft vascular occlusive sickle crisis with early renal allograft loss in occult sickle cell trait

Early renal allograft failure due to sickle cell trait is rare. We present clinical and pathologic findings in 2 cases of early renal allograft failure associated with renal vein thrombosis and extensive erythrocyte sickling. Hemoglobin AS was identified in retrospect. In case 1, a 41-year-old female recipient of a deceased donor renal transplant developed abdominal pain and acute allograft failure on day 16, necessitating immediate nephrectomy. In case 2, the transplanted kidney in a 58-year-old female recipient was noted to be mottled blue within minutes of reperfusion. At 24 hours, the patient was oliguric; and the graft was removed. Transplant nephrectomies had diffuse enlargement with diffuse, nonhemorrhagic, cortical, and medullary necrosis. Extensive sickle vascular occlusion was evident in renal vein branches; interlobar, interlobular, and arcuate veins; vasa recta; and peritubular capillaries. The renal arteries had sickle vascular occlusion in case 1. Glomeruli had only focal sickle vascular occlusion. The erythrocytes in sickle vascular occlusion had abundant cytoplasmic filaments by electron microscopy. Acute rejection was not identified in either case. Protein C and S levels, factor V Leiden, and lupus anticoagulant assays were within normal limits. Hemoglobin analysis revealed hemoglobin S of 21.8% and 25.6%, respectively. Renal allograft necrosis with intragraft sickle crisis, characterized by extensive vascular occlusive erythrocyte sickling and prominent renal vein thrombosis, was observed in 2 patients with sickle cell trait. Occult sickle cell trait may be a risk factor for early renal allograft loss.     

Renal Medullary Carcinoma and Sickle Cell Trait: A Push for Early Diagnosis and Intervention Report of Two Cases

Renal medullary carcinoma (RMC) is a rare but highly aggressive neoplasm that primarily affects young African Americans with sickle cell trait. Most patients present with macroscopic hematuria and have metastases at diagnosis. Chemotherapy, biologics directed against the more common renal cell carcinomas and radiation have all shown limited efficacy in treating patients with advanced RMC. We report two patients with RMC. Both had Stage IV disease. One underwent radical nephrectomy followed by radiation and biologic drug therapy but died five months later; the other underwent multiple cycles of chemotherapy plus anti-angiogenesis treatment but died 15 months after diagnosis. Review of the literature suggests that early diagnosis and surgical intervention while the tumor is confined to the kidney offer the best prospect for long term survival. Since newborn screening for sickle cell is now mandated in the US, the at-risk population for RMC could be identified and followed by yearly urine dipstick testing for microscopic hematuria. Those who test positive can be further evaluated to rule out RMC.     

Recurrent posterior reversible encephalopathy syndrome in a sickle cell patient

Posterior reversible encephalopathy syndrome (PRES) in sickle cell patients has been rarely reported previously in the setting of severe crisis or uncontrolled hypertension. Here, we report a rare and unusual case of recurrent PRES in a young adult sickle cell patient without any obvious precipitating factors.     

Intraosseous spindle cell hemangioma of the calcaneus: a case report and review of the literature

Spindle cell hemangioma, a rare benign tumor characterized by cavernous blood vessels and spindled areas, typically arises in the subcutis of the distal extremities, particularly the hand. The case of intraosseous spindle cell hemangioma is extremely rare, and only 1 case arises in the frontal bone has been reported previously. We describe herein a case of intraosseous spindle cell hemangioma occurring in the left calcaneus in a 65-year-old woman. The patient was successfully treated by the operation. The present case is instructive especially in the differential diagnosis of primary bone tumor structured by spindle cells, for which the possibility of spindle cell hemangioma should be considered.     

Malignant fibrous histiocytoma of bone: a study of 35 cases.

Thirty-five cases of primary malignant fibrous histiocytoma of bone are reported. Twenty of these cases were collected from a retrospective analysis of other malignant bone tumors. The age range was from 11 to 69 years; the average age was 34 years. The tumor occurred most commonly in the distal femur and proximal tibia. The distinguishing histologic feature was a storiform arrangement of spindle cells. The differential diagnosis included fibrosarcoma, osteogenic sarcoma, malignant giant cell tumor, malignant lymphoma, and metastatic carcinoma. Follow-up of at least three years was available in 21 cases. Of these, nine patients were alive and free of metastases three and one-half to 12 years after treatment. Two were alive with solitary metastases at three years, and 10 patients died between three months and three years after treatment. In four cases the lesions were multicentric at the time of diagnosis and in four cases were associated with bone infarction. This tumor must be recognized as an important complication of bone infarction and should be suspected when a patient with a known history of bone infarction develops a change in symptoms. Because the prognosis of this tumor is significantly better than that in those tumors with which it had been previously grouped, and in view of its association with bone infarction, it deserves to be maintained as a distinct clinicopathologic entity. Amputation is the treatment of choice.     

Bone marrow necrosis: an entity often overlooked

Bone marrow necrosis is a poorly understood and frequently an unrecognized finding in routine bone marrow biopsies. Previous reports indicate the incidence of bone marrow necrosis ranges from 0.5 percent (rare) to approximately one-third of all bone marrow biopsies examined. Our studies indicate that the presence of bone marrow necrosis depends on the clinical condition of the patient. Overall, our incidence of bone marrow necrosis was 37 percent of the bone marrow biopsies examined. Of these, 26.4 percent was mild. 7.5 percent moderate, and 3.1 percent severe necrosis. The mechanism in most cases had an identifiable underlying etiology such as a malignancy, or vascular or cytotoxic damage, with a small percentage being unexplained. Bone marrow necrosis is seen across a wide range of conditions, including sickle cell diseases, AIDS, leukemia, lymphoma, metastatic carcinoma, anemia, sepsis, and other systemic diseases. Patients at the extremes of age, less than 20 years and greater than 70 years, usually demonstrate only small foci of necrosis (Grade I). Moderate (Grade II) and severe (Grade III) bone marrow necrosis are often associated with life threatening illnesses, with most of these being hematologic malignancies or bone marrow metastases. The prognosis associated with bone marrow necrosis seems to be dependent on the underlying primary clinical condition regardless of the degree of necrosis observed.     

Some observations on the measurement of haemoglobin A2 and S percentages by high performance liquid chromatography in the presence and absence of alpha thalassaemia

AIMS: To assess the accuracy and precision of measuring haemoglobin A(2) by high performance liquid chromatography (HPLC) in the presence and absence of sickle cell trait, with or without alpha thalassaemia trait. METHODS: The haemoglobin A(2) percentage and the haemoglobin A(2) plus S percentages were determined by HPLC on 82 normal controls and 78 patients with sickle cell trait, respectively; the alpha thalassaemia status of each patient was determined by polymerase chain reaction. Red cell indices and haemoglobin A(2) and S percentages were compared in patients with two, three, or four alpha genes. RESULTS: Of the 78 patients with sickle cell trait, 17 were heterozygous for alpha(+) thalassaemia (-alpha(3.7)/alphaalpha) and 13 were homozygous (-alpha(3.7)/-alpha(3.7)). Microcolumn chromatography showed that the haemoglobin A(2) percentage was slightly, but significantly, higher than normal in sickle cell trait. HPLC determinations of haemoglobin A(2) percentage in patients with sickle cell trait are precise but inaccurate, the percentage being appreciably overestimated. The measured haemoglobin A(2) percentage is stable for one week, but inaccuracy increases by two weeks in most samples. Despite this inaccuracy, there are significant differences in the HPLC "haemoglobin A(2) percentage" between groups of individuals with two, three, and four alpha genes. CONCLUSIONS: Haemoglobin A(2) determinations by HPLC are precise but inaccurate. Nevertheless, there are significant differences in the haemoglobin A(2) percentage in subjects with two, three, and four alpha genes. Although there is some overlap between groups, this can be useful, together with the red cell indices, in predicting the likelihood of coexisting alpha thalassaemia.     

Mediastinal follicular dendritic cell sarcoma involving bone marrow: a case report and review of the literature

We report a rare case of mediastinal follicular dendritic cell (FDC) sarcoma involving the bone marrow. The patient, a 46-year-old woman, had a clinically aggressive tumor in the anterior mediastinum that was initially diagnosed as a diffuse B-cell lymphoma. She received chemotherapy but showed no significant improvement. One year later, the patient presented at our institution with pelvic bone metastases. Biopsy specimens of the sacrum lesion and bone marrow were obtained. The diagnosis of FDC sarcoma was made based on histological examination and immunohistochemical findings, including strong positive staining of tumor cells for CD21, CD23, clusterin, and epidermal growth factor receptor (EGFR) and negative staining for CD20, CD30, CD45, CD1a, S-100, vimentin, and keratin cocktail. Histological examination and immunohistochemical studies of a previous biopsy of the mediastinal mass confirmed the diagnosis of mediastinal FDC sarcoma. The patient was treated with an appropriate chemotherapy regimen; 1 month later, follow-up bone marrow biopsy revealed no tumor cells. Although FDC sarcoma is considered a low-grade tumor, the tumor in the present case not only developed at an unusual location with bone metastasis but also involved bone marrow. To our knowledge, this is the first such case ever reported. This case also highlights the utility of EGFR as an immunohistochemical marker of dendritic cell tumors that could be used as a diagnostic tool and guide for choosing appropriate chemotherapy regimens.     

Bone marrow necrosis in leukemic-phase follicular lymphoma

Bone marrow necrosis has been regarded as a rare entity in specimens obtained from living patients and has been associated with a poor prognosis. It is most commonly found in patients with neoplastic disorders, severe infections, and sickle cell anemia. We present an unusual case of a small-cleaved type follicular lymphoma associated with bone marrow necrosis and a leukemic phase occurring in a 55-year-old woman. Specimens were studied by morphologic, immunohistochemical, cytogenetic, and DNA hybridization techniques.     

Acute myocardial infarction caused by coronary tumor thromboembolism: a rare primary manifestation of malignant tumor disease

Myocardial infarction in the context of malignant tumor disease is rare but well documented and can occur through various pathophysiological mechanisms. We report an unusual case of a patient with recurrent myocardial infarction due to coronary tumor thromboembolism as the first clinical manifestation of a previously unknown squamous cell carcinoma of the lung. The possible pitfalls leading to a wrong preliminary diagnosis in our case as well as the literature on myocardial infarction in patients with cancer were discussed.     

Type AB thymoma accompanied by pure red cell aplasia and Good syndrome with CMV infection of tumor cells

Reported herein is a case of type AB thymoma accompanied by pure red cell aplasia (PRCA) and Good syndrome. The patient was a 55-year-old woman who was found to be anemic and to have an abnormal shadow at the left pulmonary hilus on routine medical examination. Bone marrow aspiration was performed and she was diagnosed as having PRCA. She also had hypogammaglobulinemia. The anemia was temporarily cured with oral prednisolone and cyclosporin A, and the patient underwent total thymectomy. The tumor was type AB thymoma, composed mainly of type A components; widespread spindle cell components showed slight to moderate infiltration of immature T-cells. In addition, CMV inclusion bodies were scattered throughout this tumor. The CMV-infected cells were tumor cells, because they were positive for pancytokeratin and negative for CD34. Several cases of Good syndrome with widespread CMV infection have been reported, but it is extremely rare for CMV-inclusion bodies to be found in tumor cells. No thymoma cases involving CMV infection of tumor cells have been reported.     

Myocardial infarction in sickle cell disease.

Gross and microscopic findings consistent with acute (three patients) and healed (four patients) myocardial infarction were found in seven (9.7%) of 72 consecutive hearts from patients with sickle cell disease studied after autopsy between 1950 and 1982. Gross obstructive and atherosclerotic lesions were absent in all seven patients, while microthrombi were present in the arterioles of infarcted tissue in two patients. Pathophysiological mechanisms responsible for the infarction are unclear, but anemia, platelet thrombi, coronary vasospasm, and abnormal rheology related to sickle cells may all be important. Chest pain occurred clinically in six of the seven patients and ECG findings typical of infarction were found in two patients. One patient died suddenly. These findings suggest that ischemic heart disease may be present in a significant number of patients with sickle cell disease and should be considered in all patients who complain of chest pain, whether or not the patient is in crisis.     

Transfusion support for haemoglobinopathies

The indications and management of blood transfusion in the haemoglobinopathies have been reviewed. The sickle cell diseases that require transfusion support are sickle cell anaemia, sickle haemoglobin-C and -D diseases and sickle beta-thalassaemia. Homozygous beta-thalassaemia (Cooley's anaemia) is the major problem among the thalassaemias. The pathophysiology of the sickle cell disorders is largely based on the secondary effects of increased blood viscosity, whereas in the thalassaemias the defect is ineffective haematopoiesis. In the former the major problems occur as manifestations of vaso-occlusive crises with disseminated bone and abdominal pain, priapism, stroke and leg ulcers. Bone infarction and aseptic necrosis occur but the widespread bone changes, underdevelopment and haemochromatosis that complicate the thalassaemia are not prominent. Transfusion therapy in the sickle cell diseases is mainly episodic and is guided by the frequency of crises and the severity of vaso-occlusive complications. Partial exchange transfusion and the maintenance of haemoglobin A concentrations at 40 to 50 per cent is frequently indicated. In the thalassaemias, maintenance of haemoglobin levels is essential for normal growth and development. The problem of haemochromatosis is very serious. With hypertransfusion regimens the haemoglobin and haemotocrit are maintained above 12-13 g/dl and 35 per cent. The resulting benefit appears to be reduced blood volume, less iron turnover, and less intestinal iron absorption. The splenomegaly in these disorders is frequently associated with hypersplenism requiring well-timed splenectomy. Chronic and intensive chelation is necessary to prevent the ravages of iron overload. The availability of automated equipment for in vivo and ex vivo blood cell separation has brought new possibilities for improving the management of these haemoglobinopathies. It is feasible, but not as yet practical, to offer transfusions of neocytes (red cells with a mean age of 30 days) which have a 50 per cent longer survival than routine red cell preparations (mean age of 60 days). Neocytes can be prepared ex vivo from fresh routine blood donations using blood cell separator devices. The result is reduced transfusion requirements. A more recent suggestion for using the new technology is to remove the patient's oldest and most abnormal corpuscles on the basis of buoyant density and replacing them with neocytes . Thus the short-lived abnormal red cells would be removed before they could unload their iron. With automation it is possible to perform these procedures on an outpatient basis.     

Lung volumes and diffusion capacity in sickle cell trait

Patients with sickle cell anemia have a restrictive ventilatory pattern, with reduction in diffusion capacity of the lung (DLco) and lung volumes. Diffusion capacity and lung volumes are reported as either normal or reduced in subjects with sickle cell trait. Thirteen subjects with sickle cell trait, age range 25 to 79 years, were compared with 13 normal subjects matched for age, sex, height, and smoking patterns. There was no significant difference in mean values of DLco or lung volume for the two groups. Neither was there a consistent difference for age-matched individuals. Normal lung function in sickle cell trait as opposed to sickle cell disease is probably related to the fact that the former have fewer, if any, pulmonary infectious and infarctive episodes.