Hem n Onc 8-9 (13)

Question 1

Common presenting symptoms for lymphoma include low-grade fevers, weight loss, night sweats, malaise, and cervical lymphadenopathy in an otherwise healthy young patient. The image provided with the vignette shows lymphoid cells, including Reed-Sternberg cells, which are B cells with bi- or multilobed nuclei and prominent nucleoli (commonly called “owl’s eye cells”). The proliferation of Reed-Sternberg cells is unique to ?

Answer 1

Hodgkin lymphoma and confirms the diagnosis for this patient. Reed-Sternberg cells are classically positive for CD15 and CD30. Risk factors include male gender, history of Epstein-Barr virus infection, immunodeficiency/AIDS, and prolonged use of human growth hormone.

Question 2

A t(14;18) translocation describes follicular lymphoma, which presents with a “waxing and waning” lymphadenopathy and would not show the typical Reed-Sternberg cells seen in the image.
Cytomegalovirus (CMV) can present with lymphadenopathy and a rash, and chronic Epstein-Barr virus infection appears to play a role in virtually all cases of endemic (African)
 Burkitt lymphoma and a minority of sporadic and immunodeficiency-associated cases of Burkitt lymphoma. Reed-Sternberg cells would not be found in?

Answer 2

a biopsy specimen from a patient with CMV or Burkitt lymphoma.
Lytic lesions on a skeletal survey are associated with multiple myeloma, which is another B-cell lymphoma presenting with skeletal damage and anemia, symptoms not seen in this patient.

Question 3

This patient presents with back pain, normocytic anemia, an elevated creatinine level, hypercalcemia, and lytic bone lesions detected on imaging. These findings, coupled with the proliferation of plasma cells (seen in the bone marrow biopsy specimen), are consistent with multiple myeloma.

Multiple myeloma is a malignant proliferation of plasma cells in the bone marrow that often leads to lytic bone lesions and pathologic fractures. Plasma cells are differentiated B cells that can produce and secrete?

Answer 3

large amounts of antibody specific to a particular antigen. The rough endoplasmic reticulum (RER) is the site of synthesis of secretory proteins; thus antibody-secreting plasma cells are rich in RER. Normally, there is a polyclonal distribution of immunoglobulins of different isotypes and antigen specificities in the serum. In patients with multiple myeloma, however, the majority of plasma cells are producing immunoglobulin of one isotype and antigen specifically, which can be detected as an M spike by serum protein electrophoresis.

Question 4

The free light chains (either kappa or lambda) can often be detected in the urine; this is referred to as Bence-Jones proteinuria. Patients with multiple myeloma might also have anemia, increased susceptibility to infection, or clotting abnormalities secondary to the reduced production of normal blood components. Additional possible clinical findings, as observed in this patient, include hypercalcemia and renal insufficiency (elevated creatinine), which can arise from ?

Answer 4

deposition of monoclonal protein in renal tubules.

Question 5

No other answer choice describes a feature of the malignant plasma cells in patients with multiple myeloma.
Abundant mitochondria are seen in cells with high adenosine triphosphate requirements, such as myocytes.
Abundant secondary lysosomes are seen in macrophages, which require significant amounts of hydrolytic enzymes for digestion of phagocytosed cell debris.
Abundant smooth endoplasmic reticulum is seen in hepatocytes and steroid-producing cells because ?

Answer 5

steroid hormones are produced in the smooth endoplasmic reticulum.
Abundant peroxisomes are not observed in any particular cell type but may be increased in cells that perform a significant amount of fatty acid metabolism.

Question 6

This patient’s clinical symptoms—dysphagia, fatigue, and a 15-pound weight loss—put esophageal carcinoma high on the differential diagnosis.
Her CBC shows a microcytic (low MCV), hypochromic (low MCHC) anemia. The two most common causes of microcytic anemia are iron-deficiency anemia and thalassemia. The decreased RBC and elevated RDW (which reveals how much the red cells differ in size), suggest iron-deficiency anemia, rather than mild thalassemia, in which the RBC is increased and the RDW is normal or decreased.

The upper endoscopy shows an esophageal web (the thin clear membrane at the superior aspect of the esophageal opening).

The combination of esophageal webs and iron-deficiency anemia are two parts of the triad of major findings in?

Answer 6

Plummer-Vinson syndrome. The third is atrophic glossitis, a smooth tongue caused by atrophy of filiform papillae, which occurs in long-standing iron-deficiency anemia.

Question 7

The pathogenesis of PVS remains unknown. Nutritional deficiencies and autoimmune associations have been suggested but remain unproven. Treatment includes esophageal dilation to improve the dysphagia, correction of the nutritional iron deficiency with iron supplementation, and routine surveillance with upper endoscopy, as patients with PVS are at a higher risk of developing esophageal squamous cell carcinoma.

Esophageal adenocarcinoma is usually caused by chronic acidic gastric reflux leading to the cancerous precursor Barrett esophagus, which then turns to adenocarcinoma.
Nocturnal cough and dyspnea are findings in?

Answer 7

congestive heart failure. As patients lie down, fluid which would normally settle by gravity into the lung bases are spread throughout the lung resulting in difficulty breathing.

Mallory-Weiss syndrome results from increased esophageal pressure such as in vomiting by alcoholics or bulimics, causing painful mucosal lacerations in the esophagus. These patients can also develop esophageal varices, which present as painless esophageal bleeding due to venous tearing from increased pressure in the hepatic portal system.

Question 8

This patient presents with acute projectile vomiting, severe headache, trouble walking, truncal ataxia, and papilledema. MRI of the head reveals a mass. The image demonstrates a contrast-enhanced mass arising from the midline of the cerebellum and obstructing the fourth ventricle. Gait disturbances and ataxia are results of the tumor impinging on the cerebellar vermis. Some of this patient’s other symptoms, such as headache and papilledema, arise from obstructive hydrocephalus.

Medulloblastomas, ependymomas, and hemangioblastomas are childhood primary brain tumors that can result in ?

Answer 8

hydrocephalus by obstruction of the fourth ventricle. Although both medulloblastomas and hemangioblastomas are found in the cerebellum, medulloblastomas are more common. They are also often found in the cerebellar midline in children. Medulloblastomas are a form of primitive neuroectodermal tumor and appear as small blue cells called Homer-Wright rosettes (see arrows in image). These rosettes have a high nucleus-to-cytoplasm ratio and typically surround a neuropil.

Question 9

Hemangiomas are characterized by extensive vasculature and foamy cells and may be found in the cerebellum in children, but they are usually not found in the cerebellar midline. Ependymomas demonstrate rod-shaped perinuclear inclusions that typically involve the?

Answer 9

Lining of the ventricles, without involvement of the cerebellum. Oligodendrogliomas appear histologically as cells with round centrally located nuclei surrounded by a perinuclear halo. Meningiomas show round calcifications. Both oligodendrogliomas and meningiomas are much more common in adults.

Question 10

A 47-year-old woman from the Middle East presents to the clinic with fever, general malaise, and weight loss. Physical examination reveals hepatomegaly and massive splenomegaly, along with edema. Laboratory tests show moderate anemia and a peripheral WBC count <4000/mm3. A bone marrow aspirate is drawn and sent to pathology for analysis. The results are shown in the image.

From which of the following hosts did this woman most likely acquire the parasite that she now harbors?

Answer 10

Sandfly

This patient is infected with Leishmania donovani, which is transmitted by the sandfly. Infection presents with hepatosplenomegaly, malaise, anemia, leukopenia, and weight loss. Microscopically, macrophages containing amastigotes are observed, as shown in the image. Sodium stibogluconate is used to treat L. donovani infection.

Question 11

The Anopheles mosquito transmits the Plasmodium species of protozoa that are responsible for malaria. Malaria presents with fevers accompanied by headaches, sweats, malaise, and anemia (due to lysed RBCs), but not leukopenia. Diagnosis is made by ?

Answer 11

examining the patient’s RBCs on blood films. Treatment is tailored to the geographic area of infection and the Plasmodium species involved; agents include chloroquine, hydroxychloroquine, and atovaquone-proguanil.

Question 12

The Aedes mosquito spreads the flaviviruses responsible for dengue fever and yellow fever. Dengue fever is characterized by headache, myalgais, arthralgias, and a petechial rash; laboratory tests show thrombocytompenia and a relative leukopenia. Treatment is supportive. Yellow fever presents with fever, headache, back pain, and jaundice; the best treatment is prevention via vaccination.

The Ixodes tick transmits the pathogens that cause babesiosis (Babesia microti, a protozoan), Lyme disease (Borrelia burgdorferi, a spirochete bacterium) and erlichiosis (Ehrlichia chaffeensis, a rickettsial bacterium). Infection with Babesia species presents with a malaria-like syndrome. On microscopic examination one observes the Maltese cross-appearing parasite but no RBC pigment. Quinine is used to treat babesiosis. Lyme disease classically presents with a circular, expanding rash that takes on the appearance of a bull’s eye; it can proceed to involve many organs, notably the?

Answer 12

central and peripheral nervous systems, the joints, the eyes, and the heart. Lyme disease is diagnosed by exam findings and exposure history, with corroboration from serological testing. Treatment in adults is usually with doxycycline. Erlichiosis presents with a high fever, fatigue, and myalgias, and can cause leukopenia, thryombocytopenia and renal insufficiency. Diagnosis is again by exam and exposure history, with corroboration by serological testing. Treatment is with doxycycline.

The reduviid bug spreads the protozoan Trypanosoma cruzi. Chronic infection with T. cruzi causes Chagas’ disease, a condition characterized by cardiomegaly and, often, dilation of the intestinal tract. Microscopic examination reveals flagellated trypomastigotes in the blood and nonmotile amastigotes in tissue culture. Nifurtimox is used to treat T. cruzi.

Question 13

This elderly patient presents with chronic cough, rib pain, fatigue, and unintentional weight loss. A chest X-ray reveals a rib fracture. Multiple myeloma (MM) must be on the differential diagnosis in any elderly patient with pathologic fractures. Multiple myeloma starts in the bone marrow’s plasma cells, leading to an overproduction of monoclonal IgG. The bone marrow biopsy findings are consistent with multiple myeloma, and confirm this diagnosis.
Plasma cells can be recognized by their off-center nuclei and clock-face chromatin distribution (the clock-face chromatin is not seen in the above image but is apparent at higher magnifications). Also commonly seen on a blood smear in?

Answer 13

multiple myeloma patients are stacked RBCs in what is known as a rouleaux formation. Because MM is a tumor arising from bone marrow, it causes destructive osteolytic bone lesions resulting in hypercalcemia. Hypercalcemia may manifest with symptoms of fatigue and weakness, as in this patient. Other common manifestations of multiple myeloma include anemia and renal insufficiency.

Question 14

Elevated prostate-specific antigen level (PSA) is caused by prostate cancer, benign prostatic hyperplasia, or prostatitis. Hyperkalemia could be found in patients with ?

Answer 14

significant renal insufficiency or tumor lysis syndrome. An IgM spike on serum electrophoresis could be found in hyperviscosity syndrome, caused by Waldenström macroglobulinemia. Aplastic anemia is a deficiency in all types of blood cells, caused by damage to the bone marrow’s stem cells.

Question 15

This Honduran boy has had significant weight loss and heavy night sweats. His abdomen is distended, and cervical lymph nodes are firm and enlarged. These clues, in conjunction with the soft tissue mass in the jaw and the spleen biopsy specimen showing a sheet of uniform, darkly staining lymphoma cells interspersed with pale, tingible-body macrophages, indicate Burkitt lymphoma.
Burkitt lymphoma is a rapidly growing form of B-cell, non-Hodgkin lymphoma that appears most frequently in children and young adults. Although three chromosomal translocations can be found in Burkitt lymphoma, the most common is?

Answer 15

t(8;14), which appears in about 80% of cases. That is the translocation found in this patient, who presents with the African or endemic form, which shows up most often with a rapidly growing mass in the jaw or facial bones; it also is linked to infection with Epstein-Barr virus.

Question 16

The sporadic form accounts for only 15% of cases, but is the most common form in the US. It usually manifests with abdominal involvement. Immunodeficiency-associated Burkitt lymphoma accounts for about 5% of cases and more frequently involves lymph nodes and bone marrow.

Translocation t(8;14) is diagnostic of Burkitt lymphoma and results in overexpression of c-myc. This overexpression causes rapid cellular division, giving Burkitt lymphoma the fastest rate of division of any human tumor. Histology of Burkitt lymphoma demonstrates the characteristic “starry sky” pattern created by benign, pale macrophages dispersed between the darker tumor cells.

Treatment should begin within 48 hours of diagnosis. Despite its fast-growing tumors, Burkitt lymphoma responds well to?

Answer 16

treatment with high-dose combination chemotherapy.

The other translocations are not involved in Burkitt lymphoma. The t(9;22) translocation results in the Philadelphia chromosome, which is characteristic of chronic myelogenous leukemia. Translocation t(11;14) characterizes mantle cell lymphoma. Translocation t(14;18) is commonly present in follicular lymphoma. Finally, translocation t(15;17) is commonly associated with acute promyelocytic leukemia.

Question 17

This is a 69-year-old man with a 3-month history of dizziness, tinnitus, and poor balance. CT scan reveals a mass at the cerebellopontine angle which on pathology shows compact areas of spindle cells with pink cytoplasm that form whorls and palisades. The location of the mass, its pathology and the patient’s symptoms suggest acoustic schwannoma.
Histologically, two patterns are found: (1) Antoni A, or spindle cells palisading and forming a whorl appearance (black arrow in this image); and (2) Antoni B (blue arrow), or loosely arranged tissue after degeneration in the tumor. The histopathologic description of this patient’s tumor is consistent with Antoni A.

Schwann cell tumors are the third most common primary intracranial tumor, are often localized to cranial nerve VIII (acoustic neuroma), and are commonly seen at ?

Answer 17

the cerebellopontine angle.

The most common signs and symptoms of schwannomas include hearing loss, tinnitus, vertigo, hydrocephalus, and increased intracranial pressure. Most are benign, slow-growing tumors that can be resected.

Question 18

Medulloblastoma is the most common malignant tumor in children, making it a less likely diagnosis an adult. Medulloblastoma would be found in the posterior fossa and present with headaches, nausea, vomiting, altered mental status, and sometimes cerebellar signs.

Meningiomas rarely appear in the cerebellopontine angle. They are more commonly found in the hemispheric convexities and parasagittal regions and have psammoma bodies on histopathology. Meningiomas can be asymptomatic or cause seizures or focal neurologic deficits. Symptoms are determined by the location of the mass and by the time it takes for the tumor to develop.

The patient’s acoustic schwannoma is intra-axial, while neurofibromas are of of peripheral origin. Histologically, these cells appear as loosely arranged spindle cells with intervening collagen. Neurofibromas are typically seen in?

Answer 18

a syndrome such as neurofibromatosis, which is associated with multiple café-au-lait macules and cutaneous neurofibromas.

Oligodendrogliomas are relatively uncommon tumors. They are slow growing and occur most often in the frontal lobes and present with focal signs. Oligodendrogliomas are composed of homogeneous sheets of cells with uniformly rounded nuclei and an associated network of finely branching blood vessels.

Question 19

This patient’s presentation of unintentional weight loss, fatigue, hepatosplenomegaly, as well as laboratory findings of left-shifted neutrophilia with prominent myelocytes and low alkaline phosphatase activity, are indicative of chronic myelogenous leukemia (CML). Nearly 90% of CMLs involve the creation of the Philadelphia chromosome and the fusion protein bcr-abl. BCR-ABL is a 9;22 chromosomal fusion resulting in constitutively active tyrosine kinase.

Imatinib is one of the first effective therapies to function by preventing bcr-abl activity. As a cellular oncogene, BCR-ABL codes for the combination of the breakpoint cluster region (bcr) of ?

Answer 19

chromosome 22 with the abl tyrosine kinase region of chromosome 9. The oncogene codes for abl kinase activity that is independent of cytokine regulation, which acts to promote growth, inhibit apoptosis, and increase cell turnover rate. It also regulates transcription factors that can increase the production of cell cycle proteins.

Abnormal regulation of tumor suppressor genes, DNA repair, free radical repair, and activation of transcription factors do not serve as mechanisms by which bcr-abl fusion protein produces CML.

Question 20

The patient presented with left upper quadrant pain and fatigue, while her blood work revealed high WBC, neutrophils, and basophils, suggesting a malignancy. The blood smear and lab results show a marked neutrophilic leukocytosis, consisting mostly of mature and maturing neutrophils (segmented neutrophils, metamyelocytes, myelocytes, and promyelocytes) and scattered myeloblasts. This suggests that the patient has ?

Answer 20

chronic myeloid leukemia (CML). Imatinib mesylate is a tyrosine kinase inhibitor that acts on the Philadelphia chromosome fusion protein product BCR-ABL, which is a constitutive tyrosine kinase that enables the unchecked proliferation of myeloid cells in CML.

Question 21

Many drugs act through the G protein-coupled receptor pathway, such as agents that act on autonomic a or ß receptors.
•Denosumab is an antibody used in the treatment of ?

Answer 21

osteoporosis which indirectly acts through the NF-?B pathway.
•Corticosteroids and mineralocorticosteroids act along the steroid pathway
•No medication utilizes the TGF-ß signaling pathway to exert an effect.

Question 22

The patient is presenting with pallor and mild jaundice caused by increased breakdown of red blood cells (RBCs) from ineffective erythropoiesis. The glazed appearance of the tongue represents glossitis (a shiny, “beefy” tongue, as shown in the image), while the neurologic findings suggest both motor and sensory loss in the lower limbs. The upward progression of these deficits is due to abnormal myelin from subacute combined degeneration of the spine. Lastly, her peripheral blood smear shows macrocytosis and hypersegmented neutrophils. The entirety of this clinical presentation is strongly indicative of vitamin B12, or cobalamin, deficiency. Folate (vitamin B9) deficiency can result in megaloblastic anemia with hypersegmented neutrophils, but neurologic signs and symptoms are not present. Another physical finding of B12 deficiency is angular cheilitis (fissuring at the corners of the mouth).

In patients without a clear travel history or dietary deficiency (eg, veganism), the most common cause of cobalamin deficiency is ?

Answer 22

pernicious anemia, a disorder in which dietary cobalamin is not absorbed as a result of gastric parietal cell atrophy and the subsequent absence of intrinsic factor. It is reversible in its early stages by administration of vitamin B12, but without B12 replacement, the neurologic changes will eventually become permanent.

Question 23

The other listed options are less likely causes of the patient’s B12 deficiency:

Bacterial overgrowth can lead to competition for dietary cobalamin, with signs and symptoms including bloating, flatulence, abdominal pain, and diarrhea.
Gastrectomy can result in insufficient intrinsic factor secretion and subsequent cobalamin deficiency.

Infection with the fish tapeworm Diphyllobothrium latum can also result in ?

Answer 23

competition for dietary cobalamin.
Dietary deficiency is a rare cause of cobalamin deficiency and is seen in patients who have adhered to strict vegan diets over several years.

Pancreatic insufficiency results in decreased or absent levels of pancreatic proteases, which free cobalamin from carrier proteins and allow it to bind intrinsic factor.

Question 24

This patient’s blood smear shows schistocytes, erythrocyte fragments that are found in many blood diseases. They are smaller than normal red cells and of varying shape, often having sharp angles or spines (spurs), though they are sometimes round in contour. They occur in certain genetically determined disorders (eg, thalassaemias, congenital dyserythropoietic anemia), acquired disorders of red cell formation when erythropoiesis is megaloblastic or dyserythropoietic, and in patients with cardiac valve prostheses. They also indicate?

Answer 24

mechanical trauma to the RBCs, as in this patient’s case.

Trauma to RBCs occurs in microangiopathic hemolytic anemia (MAHA), in which RBCs are forced through a microvasculature that is narrowed and obstructed. In this patient, infection with a toxic Escherichia coli strain causing bloody diarrhea resulted in hemolytic uremic syndrome (HUS), which typically causes MAHA. HUS and thrombotic thrombocytopenic purpura (TTP) are part of a larger category known as thrombotic microangiopathies.

Question 25

Antibody-mediated destruction of altered RBCs can occur with antibiotic use. Histology would show spherical RBCs, not fragmented schistocytes as depicted in MAHA.
Heinz bodies are precipitations of denatured hemoglobin, which result from decreased activity of glucose-6-phosphate dehydrogenase. Heinz bodies are plucked out by splenic macrophages, leaving RBCs looking like they have been bitten, which is why they are termed “bite cells.”
Lead toxicity can inhibit ?

Answer 25

heme synthesis, resulting in microcytic anemia rather than a normocytic anemia described by a normal mean corpuscular volume result.
Instability of RBC membranes due to an intrinsic defect, such as in hereditary spherocytosis, results in the loss of the membrane to a point where the cell becomes spherical to optimize its surface area:volume ratio.
Sickling of RBCs due to abnormal hemoglobin is classically seen in sickle cell anemia.

Question 26

The patient presents with the lesion characterized by an asymmetrical shape, irregular borders, and varied colors. It is recognizable as melanoma. She also has a history of similar skin lesions that have been removed, and she currently is demonstrating an unsteady gait and signs of numbness in her extremities.
This patient likely has?

Answer 26

xeroderma pigmentosum (XP), a condition caused by defective nucleotide excision repair proteins. People with XP suffer from numerous basal cell carcinomas, squamous cell carcinomas, and melanomas beginning at an early age. They have 2000 times the normal risk of skin cancer by age 20 years because they lack the ability to repair DNA damaged by UV light. UV radiation cross-links pyrimidine residues, and nucleotide excision is required for DNA repair of these mutations. Normal nucleotide excision repair is illustrated in the image. Up to 20% of patients with XP also have neurologic manifestations, such as unsteady gait and peripheral neuropathy mentioned in the vignette.

Question 27

BRCA1 mutations are associated with breast, ovarian, prostate, and colon cancer, whereas BRCA2 mutations are associated with breast cancer and pancreatic cancer. Nonhomologous end joining is associated with ataxia telangiectasia. DNA mismatch repair increases risk of hereditary nonpolyposis colorectal cancer, and p53 mutation increases risk of ?

Answer 27

soft tissue, breast, brain, and adrenal gland cancers. None of these mutations are associated with melanoma.

Question 28

The patient presents with a malignancy in the left eye characterized by diminished visual acuity and white pupillary reflex, often a common early sign of retinoblastoma. He is treated with radiation, but develops a similar malignancy in the right eye 2 years later. This image shows retinoblastoma (three discrete tumors, marked by arrows). Bilateral retinoblastoma is usually a sign of heritable cancer, caused by a loss-of-function mutation in the tumor suppressor gene Rb. Tumors arise when both Rb alleles are nonfunctional (two hits are needed to prevent tumor suppression).

The gene product Rb binds and inactivates E2F, a transcription factor involved in?

Answer 28

the progression of the cell cycle. Phosphorylation of Rb releases it, allowing E2F to become active. In retinoblastoma, the nonfunctional Rb results in unregulated E2F activity and, therefore, accelerated cell cycle progression. Osteosarcomas and bladder carcinomas have been to be associated with Rb mutations.

Question 29

Acute promyelocytic leukemia is associated with t(15;17) translocation, which leads to constitutively-activated retinoic acid receptors. Medulloblastoma is the most common type of pediatric brain cancer, and is associated with mutations in multiple pathways. The majority of gastric cancers involve?

Answer 29

environmental factors including H. pylori infection, smoking and diet. Pancreatic cancer is a potential manifestation of mutations of the p16 gene.