Hematological diseases Dr. T Flashcards

Question

What is this clinical presentation?

Answer 1

**Secondary Polycythemia** Oral manifestation ▪ Oral mucosa appears deep red ▪ Glossitis ▪ Gingiva appears edematous and bleeds easily ▪ Consequent “crowding out” of WBCs and platelets may result in other manifestations

Answer 2

▪ Genetic disorder of hemoglobin synthesis (one of the hemoglobinopathies) **▪ Autosomal recessive pattern** ▪ **Mutation in DNA of *thymine* for adenine causes alteration of codon resulting in the substitution of the amino acid valine for glutamic acid in the beta‐globin chain of hemoglobin** ▪ This transformed hemoglobin is prone to molecular aggregation and polymerization to form a rigid and curved shape (sickle shape)

Answer 3

* sickling of the RBCs becomes severe * precipitated by such things as **hypoxia, infection, hypothermia, or dehydration** * Symptoms include **pain (**which may be severe) due to ischemia and infarction of affected tissues ▪ Long bones, lungs and abdomen are common sites of occurrence for “crises” ▪ Episodes last from 3‐10 days, some patients have monthly crises, some may go a year or more between ▪ May need **pre‐medication prior to dental treatment** * **infections** are the most common cause of death in sickle cell patients (in the US) ▪ Patients also have impaired kidney function and CNS involvement (strokes in 5‐8%, often prior to age of 10)

Answer 4

* ▪ Transcranial Doppler scan used to evaluate blood flow in brain ▪ **Hydroxyurea** may be used as a therapy o Induces Hb F formation (doesn’t sickle) o But can be carcinogenic and teratogenic

Answer 5

* Sickle cell trait ‐ one allele is affected, only 40‐50% of hemoglobin will be abnormal, no significant clinical manifestations * **Sickle cell disease** ‐ both alleles affected, close to 100% of hemoglobin is abnormal**, significant clinical problems** ▪ **Abnormal gene** confers **resistance to malaria,** therefore**, sickle cell trait is seen most frequently in populations from areas endemic for malaria (Africa, the Mediterranean, and Asia)**

Answer 6

**Sickle Cell Anemia** Radiographic findings include: o decreased trabecular pattern in the mandible (due to increased extramedullary hematopoiesis) o laddering of inter‐radicular trabeculae o “hair‐on‐end” appearance of skull films (less prominent than with thalassemia) Can see spontaneous pulpal necrosis in the absence of trauma or caries

Answer 7

**Sickle Cell Anemia** Can see prominent trabeculae left, looks like steps on a ladder

Answer 8

▪ **Failure** of the **hematopoietic precursor cells to produce adequate numbers of all types of blood components** ▪ Rare, but life threatening ▪ **_Associated with_** **environmental toxins (benzene), certain drugs (antibiotic chloramphenicol), or infection with certain viruses (non‐A, non‐B, non‐C, non‐G hepatitis)** ▪ **Fanconi’s anemia and dyskeratosis congenita patients** _have an increased risk of developing this_

Answer 9

**Aplastic Anemia** ## Footnote ▪ Failure of the **hematopoietic precursor cells to produce adequate numbers of all types of blood components** ▪ Rare, but life threatening ▪ **_Associated with_** **environmental toxins (benzene), certain drugs (antibiotic chloramphenicol), or infection with certain viruses (non‐A, non‐B, non‐C, non‐G hepatitis)** ▪ **Fanconi’s anemia and dyskeratosis congenita patients** _have an increased risk of developing this_ **Oral signs:** are associated with the **thrombocytopenia** and include **spontaneous gingival hemorrhage, mucosal petechiae, purpura,** *and* **ecchymoses** ▪ **Nonspecific oral ulcerations** **(neutropenic ulceration)** may also be seen on any mucosal surface, but especially in areas of trauma (even minor trauma, ex. gingiva) **o Neutropenic = low neutrophils**

Answer 10

``` supportive care initially, attempts to stimulate bone marrow (androgenic steroids), and bone marrow transplants for severe cases (prognosis is guarded at best) ```

Answer 11

**Aplastic Anemia** * One of the main differences between and neutropenic ulcer and an empthis ulcer? Is the red halo, the mucosa surroundingneutropenic ulcer Is pale and not red. * The center of a neutropenic ulcer has granulation tissue with a little bit of white

Answer 12

Bleeding disorders associated with a genetic deficiency of any one of the clotting factors **o Hemophilia A (classic type, most common type )** ▪ Factor VIII deficiency ▪ X‐linked recessive ▪ Abnormal PTT **o Hemophilia B (Christmas disease)** ▪ Factor IX deficiency, ▪ X‐linked recessive, Abnormal PTT **o Von Willebrand’s disease** ▪ Abnormal von Willebrand’s factor, abnormal platelets ▪ Autosomal dominant ▪ Abnormal BT, abnormal PTT

Answer 13

**o Hemophilia A** ▪ **A patient with only 25% of normal clotting factor VIII levels may function normally, but less than 5% will likely manifest as bruising and bleeding problems** ▪ Deep hemorrhage in joints is a major complication resulting in **arthritis, ankylosis and deformity** **▪ Oral findings include bleeding** (often uncontrolled) upon scaling and root planing, tooth extractions and any oral lacerations **▪ Pesudotumor of hemophilia** o Tissue hemorrhage can result in a submucosal tumor‐like mass **o Bone hemorrhage can result in intraosseous radiolucency**

Answer 14

▪ Partial thromboplastin time (PTT), prothrombin time (PT), bleeding time (BT) and platelet counts, as well as consultation with physician, should be done prior to any dental treatment ▪ (PT is like INR, Normal INR between 0.8 and 1.2) ▪ Clotting factor replacement therapy (synthetic) given as indicated ▪ Avoid aspirin

Answer 15

Markedly decreased numbers of circulating blood platelets (severe cases \< 10,000/mm³) Etiology: Can be from: o Decreased production (malignancy, drugs) o Increased destruction (immunologic, drugs) o Sequestration in the spleen (splenomegaly)

Answer 16

▪ Clinically see spontaneous gingival bleeding, petechiae, ecchymosis and hematomas o Clinically see some type of bleeding

Answer 17

▪ Treatment is usually **platelet transfusion**

Answer 18

o hematoma because of THROMBOCYTOPENIA or Trauma

Answer 19

o hematoma because of THROMBOCYTOPENIA orTrauma

Answer 20

Hematoma ## Footnote because of THROMBOCYTOPENIA or Trauma

Answer 21

**Hematoma** because of THROMBOCYTOPENIA or Trauma

Answer 22

**Cyclic Neutropenia** ## Footnote ▪ A rare idiopathic disorder characterized by regular periodic reductions in the neutrophil population **_Etiology:_** Underlying cause is a defect in hematopoietic stem cells in the marrow _▪ Symptoms_ usually _begin in childhood_ ▪ Most symptoms when neutrophil count is at its lowest point (nadir), usually lasts 3‐6 days (even when neutrophil counts are at their highest, it’s often lower than normal) **▪ Patients have repeated problems with infections** Oral ulcerations on any mucosal surface exposed to minor trauma & can mimic recurrent aphthous ulcerations without the erythematous halo that is so typical of aphthous ▪ Gingiva is most severely affected with periodontal bone loss and tooth mobility

Answer 23

**▪ Usually a 21 day cycle** **o Dx –** when count falls below 500/ul for 4‐5 days every 21 days **▪ Patients experience recurrent fever, mallaise, anorexia, cervical lymphadenopathy, oral ulcerations, etc.** ▪ Treatment can be just supportive in mild cases, granulocyte colony‐stimulating factor for more severe cases

Answer 24

**Cyclic Neutropenia** ## Footnote Oral ulcerations on any mucosal surface exposed to minor trauma & can mimic recurrent aphthous ulcerations without the erythematous halo that is so typical of aphthous ▪ Gingiva is most severely affected with periodontal bone loss and tooth mobility

Answer 25

**Cyclic Neutropenia** ## Footnote **▪ Oral ulcerations on any mucosal surface exposed to minor trauma (L,T, BM and oropharynx) last 5‐7 days** ▪ Depending on surface involved, **can mimic recurrent aphthous ulcerations** o Usually do not see erythematous halo that is so typical of aphthous ▪ **Gingiva is most severely affected with periodontal bone loss and tooth mobility**

Answer 26

**Cyclic Neutropenia** ▪ Depending on surface involved, can mimic recurrent aphthous ulcerations o Usually do not see erythematous halo that is so typical of aphthous

Answer 27

**Cyclic Neutropenia** ▪ Gingiva is most severely affected with periodontal bone loss and tooth mobility

Answer 28

**Cyclic Neutropenia** **_o Teeth floating in air_**

Answer 29

* **Cyclic** **neutropenia** * **aggressive periodontitist** * **pamiona fav** * **burkitts lymphoma** * **langerhan cell histocytosis** **o All these things can occur in children and lead bone destructions and look like teeth are floating**

Answer 30

**Agranulocytosis** ## Footnote Decrease in the number of cells from the granular cell lineage (neutrophils, eosinophils, basophils, etc.) o Decreased production or increased destruction ▪ Some cases are idiopathic, most are drug induced ▪ Anticancer chemotherapeutics ‐ inhibit mitotic division and maturation of hematopoietic stem cells. ▪ In rare cases, agranulocytosis is a congenital syndrome. ▪ Increase risk of **infections**

Answer 31

**Agranulocytosis** **Oral findings:** * include multiple ragged ulcerations of the oral mucosa * o can mimic recurrent aphthous depending on sites involved * (but often no erythematous halo) – more like neutropenic ulcer * **Gingiva is a common site** due to the minor trauma caused bymastication (can resemble NUG)

Answer 32

**Agranulocytosis** Oral findings: * include multiple ragged ulcerations of the oral mucosa * can mimic recurrent aphthous (but often no erythematous halo) * Gingiva is a common site due -can resemble NUG)

Answer 33

**Symptoms** * ▪ Initial symptoms include non‐specific symptoms of infection **malaise, sore throat, swelling, fever, chills, etc.** * Oral findings include multiple ragged ulcerations of the oral mucosa, o can mimic recurrent aphthous but no erythematous halo, Gingiva is a common site & can resemble NUG **Treatment** * Remove offending drug, numbers should replenish in 10‐14 days * Agranulocytosis secondary to cancer therapy ‐ meticulous oral hygiene, chlorhexidine rinse (non alcohol type) , etc.

Answer 34

**▪ Represents several types of malignancies derived from hematopoietic stem cells** **▪ ~ 2.5% of all cancers in US**e

Answer 35

▪ related to crowding out of normal hematopoietic stem cells in the bone marrow o ↓ in normal WBC, RBC, and platelets ▪ See **fatigue, bleeding, bruising, fevers and infections, etc.**

Answer 36

**Divided into acute and chronic, myeloid and lymphoid** o Acute myeloid, chronic myeloid, acute lymphoid, and chronic lymphoid **▪ Acute leukemia** o Typical course under 6 mos o Untreated, runs an aggressive course often causing death **▪ Chronic leukemia** o 2‐6 or more years o More indolent course, although, they too often result in death **▪ Leukemia, like lymphoma, can cause bone destruction and the radiographic appearance of “teeth floating in air” in children**

Answer 37

Acute lymphoblastic leukemia (ALL) Success in treatment of a previously fatal disease Children age 1‐10 years have higher success with treatments than teenager do (10‐20yrs) o And infants (under 1yr) do the worst Chemotherapy that are given for curing ALL actaully causes problems when they are older.

Answer 38

**Chronic lymphocytic leukemia** o Elderly o Most common type o Considered incurable at this time o unchecked proliferation of B‐cells o no good treatment

Answer 39

``` **▪ Acute myeloid leukemia** o Adult (and children) ``` **▪ Chronic myeloid leukemia** o Peak 3rd ‐ 5th decade

Answer 40

* Probably caused by **a combination of environmental and genetic factors** * Some leukemias have specific genetic alterations (ex. **CML –** * **Philadelphia chromosome)** * **Translocation of 9 and 22 and fusion gene BCRABL1** * **Environmental factors include**: * ionizing radiation * pesticides * benzene * viruses (ex. HTLV‐1)

Answer 41

**Leukemia** Acute and chronic myelo‐monocytic leukemia are the most likely types of leukemia to exhibit oral manifestations o Generalized gingival hypertrophy May create a tumor‐like mass in soft tissue o granulocytic sarcoma/chloroma (clinically looks green) ▪ mass infiltrate into soft tissue

Answer 42

**Leukemia** ## Footnote ▪ Oral findings include **gingival hyperplasia, spontaneous bleeding of gingiva, mucosal ulcerations, candidiasis, recurrent herpetic lesions, etc**. ▪ Leukemic infiltrate in soft tissues (ex. gingiva) produces a diffuse, boggy, nontender swelling that may or may not ulcerate **o most common with myelo‐monocytic types** ▪ May create a tumor‐like mass in soft tissue o granulocytic sarcoma/chloroma (clinically looks green) ▪ mass infiltrate into soft tissue If you see children and notice they have prominent areas of redness or red/purple and know the child has decent oral hygiene, leukemia should be in your differential. Need to be aware of that cause patients need to be treated in a fairly quick fashion.

Answer 43

**Leukomia** ## Footnote o Leukemic infiltrate – have areas of erthema o Looks like gingival hyperplasia, but in gingivail hyperplasia you don’t have the same amount of redness. Leukemia has significant hyprotophy of gingivial papilla and areas that look like they have ptechia in them. With gingival hyperplasia drug induced they are very fibrotic

Answer 44

**Leukemia** o Dilantin hyperplasia (drug induced gingival hyperplasia) – fibrotic looking o Has to an addition of thromocytopenia

Answer 45

**Leukemia** This is **Chloroma**, inflitrate gets so dense they look green. On buccal or lingual mucosa chloroma are more of a solitary mass, gingival it more diffuses

Answer 46

leukomia Cause of infiltrate they has bone loss

Answer 47

leukomia o Multifocal bony destruction o Widened PDL with leukemic infiltrate ▪ Symmetric widening of PDL space in a patient that doesn’t have that normal vertical bone loss that you associate with periodontal disease. ▪ If see symmetrical bone loss in PDL space think malignancy, neoplastic **● Lymphomas, leukemias, osteocarcoma, chondro scaroma can do this**

Answer 48

Adult acute myeloid leukemia (AML) is a type of cancer in which the bone marrow makes a large number of abnormal blood cells. We see in these images: o Hemorrhagic ulcer right vestibule o Ulcers are deep and can go down to bone o Ulcers resolved after treatment

Answer 49

* **Treatment** depends on specific type of leukemia, but includes multi‐agent chemotherapy (often an initial high dose induction and then a lower maintenance dose) * And for lymphoma * **Bone marrow transplant** has been used with limited success

Answer 50

**Non‐Hodgkins Lymphoma (NHL)** ## Footnote o The most common of the lymphoproliferative diseases o Uncontrolled proliferation of B or T cell origin derived from a single cell (or clone) o Typically presents with painless lymphadenopathy (often unilateral) ▪ up to 40% are extranodal ▪ 5‐10% arise in Waldeyer’s ring

Answer 51

Non‐Hodgkins Lymphoma (NHL) o The most common of the lymphoproliferative diseases o Uncontrolled proliferation of B or T cell origin derived from a single cell (or clone) o Typically presents with painless lymphadenopathy (often unilateral) ▪ up to 40% are extranodal ▪ 5‐10% arise in Waldeyer’s ring

Answer 52

Non‐Hodgkins Lymphoma (NHL) o Typically presents with painless lymphadenopathy (often unilateral) ▪ up to 40% are extranodal ▪ 5‐10% arise in Waldeyer’s ring ▪ _Inflamatory or reactive enlarged lymph nodes_ tend to be * *soft, tender, and movable** * *▪** _Lymph nodes associated with malignancy_ tend to be * *hard/firm, fixed, and non‐tender**

Answer 53

* **Low grade B cell** (disseminated but slow growing) * Small lymphocytic, Mantle cell, Marginal zone * Follicular center (35‐40 % of all B cell lymphomas) * **Moderate** (aggressive) * Diffuse B‐cell, Peripheral T‐cell * **High Grade B cell** (disseminated and rapidly progressive) * Anaplastic large cell, lymphoblastic * Large cell (25‐30 % of all B cell lymphomas) * Burkitt’s * Immunoblastic (increasingly seen in AIDS) * As AIDS patients live longer we see this more * **T cell lymphoma** (less common than B cell, associated with **palatal perforation** [midline lethal granuloma]) (in differntial with deep fungal infections/candidiasis, TB, use of cocaine * Precursor T‐lymphoblastic, T cell chronic lymphocytic, * **Hodgkin’s** (bimodal ‐ late twenties and after 50 years old)

Answer 54

**Burkitt’s Lymphoma** **African type (endemic**) * More common * Peak incidence 3‐8 years of age * _Twice as common in males_ * **~95% associated with the Epstein‐Barr virus** * North american or non edemic type is not associated * with EBV * ~88% under 3 yrs of age have jaw lesions * Only 25% of those older than 15 do * Typically involves: * MD, MX, (often affects all 4 quadrants) * Mandible or maxilla * Abdomen * grow quickly

Answer 55

Burkitt’s Lymphoma * **North American type (sporadic)** * Typically older children (mean of 11 years) * Involves abdomen as a mass * uncommon in the jaws * No association with EBV * More localized disease * **HIV type** * Adults * 25% associated with EBV * GI, marrow and CNS **Teeth floating** as shown in the image

Answer 56

**Burkitt’s Lymphoma** Scattered throughout the lymphocytes are macrophages containing nuclear debris (tingible body macrophages) o Creates **a “starry sky”** appearance

Answer 57

**T cell Lymphoma** _Less common than B cell lymphomas_ ▪ One variant associated with **palatal perforation** o Old name **midline lethal granuloma**

Answer 58

* Midline lethal granuloma (T cell Lymphoma) * deep fungal * malignancy * TB * tertiary syphilis gumma, * cocaine abuse (necrotizing sialometaplasia‐ soft * tissue)

Answer 59

**Hodgkin Lymphoma** ## Footnote **▪ Cell of origin is unknown** ▪ Often begins as a unifocal disease above diaphragm and then spreads to other sites ▪ Present with painless cervical lymphadenopathy in 60‐80% of cases ▪ **Bimodal ‐ late twenties and after 50 years old** ▪ In North America and Europe, **EBV positivity has been noted in over 50 percent of mixed cellularity cases and 10 to 50 percent of nodular sclerosis cases**

Answer 60

**Hodgkin Lymphoma** **o Begins in lymph nodes o 70‐75% cervical/supraclavicular o Painless but unresolving,** **o Night fevers/sweats**

Answer 61

**Hodgkins lymphoma**

Answer 62

▪ Stage I and II – localized disease curable with RT ▪ Stage III and IV – more widespread and treated with chemo and RT, worse prognosis ▪ Stage determined by sites involved o Above diaphragm – stage 1 and 2 o Above and Below diaphragm – stage 3 and 4 having it above diaphragm is bette than having it below so stage 1 and 2 are better than stage 3 and 4

Answer 63

**Plasma Cell Disorders** Clock face nucleaus

Answer 64

**Plasma cell gingivitis** ▪ Allergen causes mass infiltrate into gingival ▪ Benign ▪ Diet log to identify allergen, allergy testing

Answer 65

**Plasma cell gingivitis** ▪ Allergen causes mass infiltrate into gingival ▪ Benign

Answer 66

**▪ Diet log** to **identify allergen,** allergy testing ▪ Ideally **eliminate offending substance** ▪ **Can manage with topical steroids**

Answer 67

**Multiple Myeloma** Monoclonal expansion of malignant plasma cell ▪ Most common in 40‐70 year old (mean 63 yo.) ▪ Present with bone pain (\> 70%) and pathologic fractures Punched out radilucency

Answer 68

▪ **Bones** most commonly involved include **ribs, vertebrae and skull** **o 70‐90% will have jaw involvement at some point** ▪ **Anemia, thrombocytopenia and neutropenia** due to crowding out of normal cells within bone marrow by proliferating malignant cells ▪ **50‐60% have Bence‐Jones proteins in urine** (light chains, usually kappa) **o Due increased plasma cells ⇒ plasma cells make antibodies ⇒ antibodies/proteins gets excreted** **Solitary plasmacytoma can be the first sign of multiple myeloma** ▪ Radiographically, see **punched out radiolucencies** (no sclerotic margin) often with an irregular outline

Answer 69

Multiple Myloma ## Footnote **Punched out translucency in crest**

Answer 70

Multiple myeloma

Answer 71

Multiple Myeloma

Answer 72

Multiple Myeloma **Pathological fracture**

Answer 73

Multiple Myeloma Elevated M spike in serum ‐ abnormal increase in immunoglobulin (**hyperglobulinemi**a), most commonly IgG ▪ Reversal of normal albumin/globulin ratio

Answer 74

* **Chemotherapy** with or without RT * **Bone marrow transplant,** interferon, antibodies made * against tumor cells, thalidomide, bisphosphonates, * corticosteroids, melphalan, etc. * Even with treatment, most patients do not survive more than * 18‐24 months * older patients – better prognosis * younger patients – more aggressive and worse prognosis * IV bisphosphonate therapy puts patients at increase risk for MRONJ

Answer 75

**Multiple Myeloma** Deposition of amyloid in soft tissues o Can cause macroglossia if tongue is involved

Answer 76

**Plasmacytoma** **▪ Unifocal, monoclonal neoplastic ▪ proliferation of plasma cells** **▪ 30% develop into MM over 10 yrs ▪ 50% disseminate w/in 2‐3 yrs ▪ Central Bone lesion o Unilocular radiolucency o Swelling or bone pain o Non‐tender soft tissue mass** **▪ 90% occur in Head and neck**

Answer 77

▪ Tx: **radiation**, better prognosis than MM ▪ Solitary better prognosis than disseminated MM

Answer 78

* Immune cell tumors primarily involving bone marrow and peripheral blood are classified as leukemias * while those of lymph nodes are classified as lymphomas, * however there is often overlap of these entities