EUH Hunt Conference: Review of Meigs’ Syndrome

Bottom Line: Meigs’ syndrome is also known as Meigs syndrome or Demons-Meigs syndrome. It is characterized by a triad of ascites, pleural effusion, and benign ovarian fibroma, which is a rare triad. “Meigs syndrome…is a diagnosis of exclusion only after ovarian carcinoma is ruled out. The presentation of symptoms and radiographic findings mimics that of metastatic ovarian cancer, creating a significant clinical challenge….The treatment is exploratory laparotomy that includes biopsy of the ovarian mass, lymph node biopsies, biopsy of omentum, and pelvic washings. Unilateral salpingo-oophorectomy is performed in women of reproductive age, whereas total hysterectomy is preferred in postmenopausal women. The prognosis of Meigs syndrome is good and <1% of fibromas progress to fibrosarcoma. The pleural effusion and ascites resolve within a few weeks after tumor resection. We favor the use of chest ultrasound to follow pleural effusion progression, as it is superior to chest x-rays in identifying residual pleural effusion and can detect amounts as small as 3 to 5 mL.” The article reports a case of a patient with recurrent pleural effusions and an ovarian mass. It describes the case in detail and reviews the literature on Meigs syndrome.

Reference:
Riker D, Goba D. Ovarian mass, pleural effusion, and ascites: revisiting Meigs syndrome. J Bronchology Interv Pulmonol. 2013 Jan;20(1):48-51.

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EUH Hunt Conference: What is the sensitivity of cytology tests of pleural effusion and ascites?

Bottom Line: Sensitivity of ascitic cytology is approximately 60%, and the sensitivity of pleural effusion cytology is approximately 50%.

References:

Karoo RO, Lloyd TD, Garcea G, Redway HD, Robertson GS. How valuable is ascitic cytology in the detection and managent of malignancyPostgrad Med. 2003 May;79(931):292-294. Study included 276 samples.

Motherby H, Nadjari B, Friegel P, Kohaus J, Ramp U, Bocking A. Diagnostic accuracy of effusion cytology. Diagn Cytopathol. 1999 Jun;20(6):350-357. Study included 300 pleural effusions and 300 ascitic effusions and provides sensitivity for both types of effusions.

 

VA Resident Report: What is the management strategy of Kaposi Sarcoma and pneumocystis pneumonia in a HIV positive patient?

The Bottom Line:

The management of pulmonary KS is challenging. There is a risk of precipitating IRIS upon initiating cART. Chemotherapy can also cause further immunosuppression and increase the risk of further infections. In many of these patients, initiation of cART with careful monitoring for IRIS and empiric treatment of suspected infections may be the best therapeutic option. In some patients, there was a hesitancy to start cART if there was a history of poor medication adherence. Many of these patients required prolonged hospitalization, where their adherence could have been carefully monitored and encouraged.

Kasturia, S., Gunthel, C., Zeng, C., & Nguyen, M. (n.d.). Severe Kaposi Sarcoma in an Urban Public Hospital. AIDS Research and Human Retroviruses, 33(6), 583-589.

The majority of patients were highly immunosuppressed when KS was diagnosed (median CD4 count: 11), and 68% had multiple organ involvement with KS. Comorbidities at diagnosis included hepatitis B (26%) and pneumocystis pneumonia (33%). Frequent reasons for admission included skin and soft tissue complaints (28.4%) and respiratory complaints (27.2%). The estimated median survival after KS diagnosis was 3.0 years. Lung involvement, liver involvement, poor performance status, and low CD4 T cell count (<50) were associated with lower survival.

VA Resident Report: Can depleted uranium rounds cause cancer?

The risk of fatal cancer for the maximally exposed Level I veteran is 1.4% (upper bound of 3.5%). Almost all of the DU-induced cancer risk is associated with the risk incurred for lung cancer. DU fragments are predicted to increase non-respiratory system cancer risks. However, even for the maximum case with fragments included, the risks for all other cancer types are very small.

Table 6. Predicted incremental fatal cancer risks for veterans from internalized DU radiation exposure compared to percentage of all US civilian fatalities from cancer.

Marshall, A. (n.d.). Gulf war depleted uranium risks. Journal of Exposure Science and Environmental Epidemiology., 18(1), 95-108.

US and British forces used depleted uranium (DU) in armor-piercing rounds to disable enemy tanks during the Gulf and Balkan Wars. Uranium
particulate is generated by DU shell impact and particulate entrained in air may be inhaled or ingested by troops and nearby civilian populations. As
uranium is slightly radioactive and chemically toxic, a number of critics have asserted that DU exposure has resulted in a variety of adverse health effects
for exposed veterans and nearby civilian populations.

VA Resident Report: What is the association between squamous cell carcinoma and acquired factor VIII?

Following surgery for the patient in this case study, the tumor nor the coagulation inhibitor has recurred after 6 months’ follow-up. While it is possible that the inhibitor may have remitted spontaneously or remained in remission because of the therapy given before surgery, the inhibitor’s appearance as the tumor grew and the remission of the tumor as well as of the inhibitor after surgery suggest a causal relationship. As with other factor VIII inhibitors seen with other types of malignancy, it is very unlikely that the tumor was producing the antibody but rather that the tumor induced an autoimmune reaction in the patient.

Shastri, K., Logue, G., Zeid, M., Behrens, A., Lenahan, E., & Haar, J. (n.d.). Acquired factor VIII inhibitor with squamous cell cancer of the epiglottis. Archives of Otolaryngology–head & Neck Surgery., 116(3), 350-353.

A variety of malignancies have been associated with acquired factor VIII inhibitors, including lymphoproliferative diseases6-7 and solid tumors such as those of lung,8 prostate,9 colon,5 and kidney.5 The patient described here developed the acquired inhibitor in conjunction with head and neck carcinoma, specifically squamous cell carcinoma of the epiglottis. This specific association has not been previously reported, to our knowledge. Approximately 12 weeks before the discovery of the head and neck malignancy, the patient had a normal coagulation profile. When the malignancy was discovered, her APTT had risen to approximately twice the normal. Further in vitro testing, described above, documented an IgG antibody that inhibited factor VIII function.

VA Resident Report: What is the etiology and therapy options for Postobstructive community-acquired pneumonia?

The Bottom Line: This study encourages more limited antibiotic use in patients with PO-CAP. Our experience has been that when patients fail to respond to a first course of antibiotics, physicians repeat sputum cultures, which now are contaminated with newly acquired gram-negative colonizing organisms, and then give additional antibiotics to cover these newly recognized bacteria

Abers, M., Sandvall, B., Sampath, R., Zuno, C., Uy, N., Yu, V., . . . Musher, D. (n.d.). Postobstructive Pneumonia: An Underdescribed Syndrome. Clinical Infectious Diseases, 62(8), 957-961.

Postobstructive pneumonia, a pulmonary infiltrate distal to a bronchial obstruction that, in adults, is generally due to malignancy, has been reported in about 2% of patients hospitalized for community-acquired pneumonia (CAP). Opinion varies as to whether infection is responsible for POCAP. Some believe that infection is generally not involved, whereas others regard bacterial infection as the usual cause. Because conventional practice is to treat all POCAP with antibiotics, we performed a prospective study to characterize the clinical and laboratory findings in patients with this disease, with particular attention to the role of bacterial infection.

Review of advancements in treating Multiple Myeloma (MM)

The Bottom Line: New diagnostic criteria, a Revised International Staging System, and the approval of three drugs (four others pending approval) have greatly advanced the treatment, diagnosis, staging, risk-stratification and management of MM. These changes, as well as others detailed in this article, have altered how MM and smoldering multiple myeloma (SMM) are defined.

Reference: Rajkumar, S. Vincent. Myeloma today: Disease definitions and treatment advances. Am J Hematology. 2015 Nov 13; (Accepted article). doi: 10.1002/ajh.24236.

Summary: This review article takes you through the advancements in great detail, including an explanation of the old regimen and how the advances came to be. New diagnostic criteria involve three biomarkers: bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain ratio ≥100, and >1 focal lesion on magnetic resonance imaging.

The Revised International Staging System “combines markers of tumor burden (albumin, beta-2 microglobulin) with markers of aggressive disease biology (high risk cytogenetics and elevated serum lactate dehydrogenase).”

The approval of  carfilzomib, pomalidomide, and panobinostat (elotuzumab, daratumumab, and ixazomib are pending approval) combined with the older agents (cyclophosphamide, dexamethasone, thalidomide, bortezomib, and lenalidomide)  “dramatically increases the repertoire of regimens” available for treatment at each stage.

Weight gain and oxygen failure in ATRA differentiation syndrome

Supportive measures are also crucial in the correct management of differentiation syndrome. In the PETHEMA protocols, furosemide is usually administered to treat signs or symptoms of fluid overload. Some cases with refractory acute renal failure and/or fluid overload may need renal replacement therapy and in patients at risk for fluid overload and high requirements of blood products to control the coagulopathy, the use of cryoprecipitate, fibrinogen, and other coagulation factor concentrates instead of fresh-frozen plasma may be considered. Invasive, but also noninvasive, mechanical ventilation is indicated in some patients with severe acute respiratory failure who do not respond to high-flow oxygen therapy. In our experience,6 diuretics, dialysis, and mechanical ventilation were needed in 87%, 12%, and 26% of patients with DS,

Sanz MA, Montesinos P. How we prevent and treat differentiation syndrome in patients with acute promyelocytic leukemia. Blood. 2014 May 1;123(18):2777-82. doi: 10.1182/blood-2013-10-512640. Epub 2014 Mar 13.

Differentiation syndrome, formerly known as retinoic acid syndrome, is a relatively common and potentially severe complication seen in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and/or arsenic trioxide. The full-blown syndrome consists of unexplained fever, weight gain, dyspnea with pulmonary infiltrates, pleuropericardial effusion, hypotension, and renal failure. Most measures currently used for management of Differentiation syndrome have very little evidence-based support, and therefore, many remain controversial

jkn 2/16

How to distinguish multiple myeloma and amyloidosis

Multiple myeloma is a malignant plasma cell tumor, which ranks second in terms of prevalence among the hematologic malignancies. Diagnostic criteria includes occurrence of a monoclonal component detectable on serum and/or urine electrophoresis, light chain restricted bone marrow plasmacytosis, and the demonstration of related organ or tissue impairment shown by increased calcium, renal failure, anemia, and bone lesions. The staging procedure, whereby demonstration of skeletal sparing or at most a solitary osteolytic lesion allowed a multiple myeloma patient to be defined as stage I and, conversely, the occurrence of multiple osteolytic lesions was sufficient by itself to assign a patient to stage III. This staging system has been extensively used for approximately 30 years for its prognostic implications and as a reliable tool of patient stratification in clinical trial research. Recently, in step with the introduction of more accurate and advanced imaging techniques, an updated anatomic and functional Durie and Salmon ‘‘plus’’ staging system has been established, which allows a better classification of patients with early stage multiple myeloma, who can more easily be differentiated from those with monoclonal gammopathy of undetermined significance or smoldering myeloma; a better discrimination among patients with stage II or stage III multiple myeloma, based on the occurrence of more than 20 focal lesions and/or extra-medullary disease

At least twenty-three different unrelated proteins exhibit amyloidogenic properties, in that their low molecular weight subunits may become amyloid fibers and undergo extra-cellular deposition in localized or systemic fashion, eventually resulting in functional impairment of the affected organ(s) . Localized amyloidosis involves more frequently single districts, for example, larynx, ureter, skin, eyelid, and cardiac atria, and is characterized by the occurrence of foci of monoclonal plasma cells that synthesize amyloidogenic light chains. It is conceivable that giant cells are able to misfold these chains to AL amyloid fibrils. Systemic amyloidosis, on the other hand, is structurally heterogeneous and includes three main types: 1. AL amyloidosis, formed by lambda and less often kappa light chains, produced in the course of a usually indolent monoclonal B cell expansion; 2. AA amyloidosis, whose precursor is the acute phase protein SAA, synthesized in excess by the liver following chronic inflammatory and infectious conditions; 3. ATTR amyloidosis that results from a point mutation of the precursor protein transthyretin secreted by the liver, a carrier of retinol-binding protein and thyroxine in the blood and a ‘‘negative’’ acute phase protein. By definition, systemic amyloidosis can virtually affect many organs and tissues, and most frequently kidneys, liver, heart, lungs, nerves, and spleen.

Dammacco, Franco, et al. Clinical and Experimental Medicine 15.1 (2015):1-18.

Review of peripheral t cell lymphomas; clinical staging for common types of non-Hodgkin’s lymphoma (NHL); staging of NHL

Longo, DL. Chapter 110. Malingnancies of Lymphoid Cells. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012.

Peripheral T Cell Lymphoma

The peripheral T cell lymphomas make up a heterogeneous morphologic group of aggressive neoplasms that share a mature T cell immunophenotype. They represent ∼7% of all cases of non-Hodgkin’s lymphoma. A number of distinct clinical syndromes are included in this group of disorders. Table 110–10 shows the clinical characteristics of patients with peripheral T cell lymphoma.

The diagnosis of peripheral T cell lymphoma, or any of its specific subtypes, requires an expert hematopathologist, an adequate biopsy, and immunophenotyping. Most peripheral T cell lymphomas are CD4+, but a few will be CD8+, both CD4+ and CD8+, or have an NK cell immunophenotype. No characteristic genetic abnormalities have yet been identified, but translocations involving the T cell antigen receptor genes on chromosomes 7 or 14 may be detected. The differential diagnosis of patients suspected of having peripheral T cell lymphoma includes reactive T cell infiltrative processes. In some cases, demonstration of a monoclonal T cell population using T cell receptor gene rearrangement studies will be required to make a diagnosis.

The initial evaluation of a patient with a peripheral T cell lymphoma should include the studies in Table 110–11 for staging patients with non-Hodgkin’s lymphoma. Unfortunately, patients with peripheral T cell lymphoma usually present with adverse prognostic factors, with >80% of patients having an IPI score ≥2 and >30% having an IPI score ≥4. As this would predict, peripheral T cell lymphomas are associated with a poor outcome, and only 25% of the patients survive 5 years after diagnosis. Treatment regimens are the same as those used for diffuse large B cell lymphoma (omitting rituximab), but patients with peripheral T cell lymphoma have a poorer response to treatment. Because of this poor treatment outcome, hematopoietic stem cell transplantation is often considered early in the care of young patients.

A number of specific clinical syndromes are seen in the peripheral T cell lymphomas. Angioimmunoblastic T cell lymphoma is one of the more common subtypes, making up ∼20% of T cell lymphomas. These patients typically present with generalized lymphadenopathy, fever, weight loss, skin rash, and polyclonal hypergammaglobulinemia. In some cases, it is difficult to separate patients with a reactive disorder from those with true lymphoma.

Extranodal T/NK cell lymphoma of nasal type has also been called angiocentric lymphoma and was previously termed lethal midline granuloma. This disorder is more frequent in Asia and South America than in the United States and Europe. EBV is thought to play an etiologic role. Although most frequent in the upper airway, it can involve other organs. The course is aggressive, and patients frequently have the hemophagocytic syndrome. When marrow and blood involvement occur, distinction between this disease and leukemia might be difficult. Some patients will respond to aggressive combination chemotherapy regimens, but the overall outlook is poor.

Enteropathy-type intestinal T cell lymphoma is a rare disorder that occurs in patients with untreated gluten-sensitive enteropathy. Patients are frequently wasted and sometimes present with intestinal perforation. The prognosis is poor. Hepatosplenic γδ T cell lymphoma is a systemic illness that presents with sinusoidal infiltration of the liver, spleen, and bone marrow by malignant T cells. Tumor masses generally do not occur. The disease is associated with systemic symptoms and is often difficult to diagnose. Treatment outcome is poor. Subcutaneous panniculitis-like T cell lymphoma is a rare disorder that is often confused with panniculitis. Patients present with multiple subcutaneous nodules, which progress and can ulcerate. Hemophagocytic syndrome is common. Response to therapy is poor. The development of the hemophagocytic syndrome (profound anemia, ingestion of erythrocytes by monocytes and macrophages) in the course of any peripheral T cell lymphoma is generally associated with a fatal outcome.

Harrison’s Principles of Internal Medicine, 18e > Chapter 110. Malignancies of Lymphoid Cells

Table 110–10 Clinical Characteristics of Patients with Common Types of Non-Hodgkin’s Lymphomas (NHL) Disease Median Age, years Frequency in Children % Male Stage I/II vs III/IV, % B Symptoms, % Bone Marrow Involvement, % Gastrointestinal Tract Involvement, % % Surviving 5 years
B cell chronic lymphocyticleukemia/small lymphocytic lymphoma 65 Rare 53 9 vs 91 33 72 3 51
Mantle cell lymphoma 63 Rare 74 20 vs 80 28 64 9 27
Extranodal marginal zone B cell lymphoma of MALT type 60 Rare 48 67 vs 33 19 14 50 74
Follicular lymphoma 59 Rare 42 33 vs 67 28 42 4 72
Diffuse large B cell lymphoma 64 ~25% of childhood NHL 55 54 vs 46 33 16 18 46
Burkitt’s lymphoma 31 ~30% of childhood NHL 89 62 vs 38 22 33 11 45
Precursor T cell lymphoblastic lymphoma 28 ~40% of childhood NHL 64 11 vs 89 21 50 4 26
Anaplastic large T/null cell lymphoma 34 Common 69 51 vs 49 53 13 9 77
Peripheral T cell non-Hodgkin’s lymphoma 61 ~5% of childhood NHL 55 20 vs 80 50 36 15 25

Abbreviation: MALT, mucosa-associated lymphoid tissue.

Table 110-11 Staging Evaluation for Non-Hodgkin’s Lymphoma

Physical examination
Documentation of B symptoms
Laboratory evaluation
Complete blood counts
Liver function tests
Uric acid
Calcium
Serum protein electrophoresis
Serum β2-microglobulin
Chest radiograph
CT scan of abdomen, pelvis, and usually chest
Bone marrow biopsy
Lumbar puncture in lymphoblastic, Burkitt’s, and diffuse large B cell lymphoma with positive marrow biopsy
Gallium scan (SPECT) or PET scan in large cell lymphoma

Abbreviations: PET, positron emission tomography; SPECT, single photon emission CT.