**5. Hematologic disorders**

The common hematologic disorders that need IHC stains are;


### **5.1. Hodgkins lymphoma**

**4.8. Granular cell tumor**

polypoid, and measure from1 to 2 cm.

324 A Textbook of Advanced Oral and Maxillofacial Surgery Volume 2

*4.8.2. Immunohistochemical stains*

This is an uncommon tumor composed of poorly demarcated granular cells, thought to be Schwann-cell derived, that frequently arise below a mucosa, the latter often showing pseu‐ doepitheliomatous hyperplasia. Granular cell tumor tends to affect the oral cavity (tongue most commonly). Tumors are usually smooth surfaced, poorly demarcated, and are often

The neoplastic cells yield a strong and diffuse nuclear and cytoplasmic S-100 protein reaction

a) b)

**•** Extranodal NK/T-Cell lymphoma, (angiocentric T-cell lymphoma) Midline lethal granulo‐

**Figure 22.** a) Polygonal granular cells H&E b) neoplastic ells with s-100

The common hematologic disorders that need IHC stains are;

**5. Hematologic disorders**

**•** Non – Hodgkin's lymphoma

**•** Hodgkin's lymphoma

**•** Burkitt's lymphoma

ma

and are also positive for CD68, NSE, α-1–antitrypsin [17-19, 62] (Figure 22).

*4.8.1. Definition*

This almost always begins in the lymph nodes, and any lymph node group is susceptible.

The most common sites of initial presentation are the cervical and supraclavicular nodes (70% to 75%). Hodgkin's lymphoma is currently classified in the following manner:


The antibodies most commonly used for diagnosing HL are Ber-H2 (CD30), LeuM1 (CD15), LCA (CD45), L26 (CD20), CD75 (LN1), CD74 (LN2), PAX5, CD3, UCHL1 (CD45RO), ALK, fascin, and EBV-LMP1. EMA and CD57 can be used to recognize NLPHL.

Monoclonal antibody LN1 reacts with H/RSCs in approximately one third of HL cases, most frequently in cases of NLPHL (>75% of cases)(Figure 23). [17-19]

**Figure 23.** a) Hodgkin/Reed-Sternberg cells b) antigenic Reed-Sternberg cells for CD15

### **5.2. Non- Hodgkins lymphoma**

#### *5.2.1. Definition*

Non-Hodgkin's lymphoma most commonly develops in the lymph nodes, In the oral cavity. Lymphoma usually appears as extranodal disease. The malignancy may develop in the oral soft tissues or centrally within the jaws; they most commonly affect the buccal vestibule, posterior hard palate, or gingiva.

## *5.2.2. Immunohistochemical stains*

#### **Small Cell Lymphoid Neoplasms**

The lymphoma cells express pan–B-cell antigens (CD19, CD20, CD22, PAX-5). Mantle cell lymphoma (MCL) expresses pan–B-cell antigens (CD19, CD20, CD22), CD5, CD43, Bcl-2, and cyclin D1.

Nodal marginal zone lymphoma (NMZL) will typically express pan–B-cell antigens that include CD19, CD20, PAX5, and CD79a;

Co-expression with Bcl-2 and CD43 is common and occurs in 50%. The vast majority of lowgrade follicular lymphoma (FL) are positive for Bcl-2 small lymphocytic lymphoma (CLL/SLL) includes expression of CD5, CD23, CD19, CD43, and Bcl-2 and has a proliferation rate of less than 10%. [17-19] (Figure 24).

### **Large B-Cell Lymphoid Neoplasms**

CD15 expression +

CD30 +

CD45 expression +

PAX5 strong, uniform + CD20 strong, uniform +.

CD79a expression +.

p63 +

**Figure 24.** a) B-cell lymphoma (H&E) b) CD 20 is positive

### **T-Cell Lymphoid Neoplasms**

Almost all peripheral T-cell lymphomas express pan–T-cell antigens CD3, CD2, and CD43. Anaplastic large-cell lymphoma (ALCL) is positive for CD30, and the expression should be strong and in at least 75% of the cells.

The neoplastic cells of angioimmunoblastic T-cell lymphoma)AITL) are positive for pan–T-cell antigens CD3, CD2, CD5, [17-19]

### **5.3. Extranodal NK/T-cell lymphoma, (angiocentric T-cell lymphoma) midline lethal granuloma**

### *5.3.1. Definition*

*5.2.2. Immunohistochemical stains*

cyclin D1.

**Small Cell Lymphoid Neoplasms**

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include CD19, CD20, PAX5, and CD79a;

than 10%. [17-19] (Figure 24).

CD15 expression +

CD45 expression +

CD79a expression +.

CD30 +

p63 +

**Large B-Cell Lymphoid Neoplasms**

PAX5 strong, uniform + CD20 strong, uniform +.

**Figure 24.** a) B-cell lymphoma (H&E) b) CD 20 is positive

**T-Cell Lymphoid Neoplasms**

strong and in at least 75% of the cells.

antigens CD3, CD2, CD5, [17-19]

The lymphoma cells express pan–B-cell antigens (CD19, CD20, CD22, PAX-5). Mantle cell lymphoma (MCL) expresses pan–B-cell antigens (CD19, CD20, CD22), CD5, CD43, Bcl-2, and

Nodal marginal zone lymphoma (NMZL) will typically express pan–B-cell antigens that

Co-expression with Bcl-2 and CD43 is common and occurs in 50%. The vast majority of lowgrade follicular lymphoma (FL) are positive for Bcl-2 small lymphocytic lymphoma (CLL/SLL) includes expression of CD5, CD23, CD19, CD43, and Bcl-2 and has a proliferation rate of less

a) b)

Almost all peripheral T-cell lymphomas express pan–T-cell antigens CD3, CD2, and CD43. Anaplastic large-cell lymphoma (ALCL) is positive for CD30, and the expression should be

The neoplastic cells of angioimmunoblastic T-cell lymphoma)AITL) are positive for pan–T-cell

**NK/T-cell lymphoma** is the most common malignant nonepithelial neoplasm found in the upper respiratory tract and most commonly involves the nasal cavity, the maxillary sinus, nasopharynx, and salivary gland. This discussion will be limited to extranodal NK/T-cell lymphoma, nasal type (NK/T LNT), which is more common in the sinonasal region.

### *5.3.2. Immunohistochemical stains*

NK cells express CD2, CD7, CD8, CD56, and CD57. They are positive for cytoplasmic CD3, but not surface CD3, and do not typically express CD5. The neoplastic counterpart, extranodal NK/T-cell lymphomas, express CD2, cytoplasmic CD3, CD56, and, in most cases, EBV. [17-19] (Figure 25, 26).

**Figure 25.** a) Extranodal natural killer/T-cell lymphoma b) CD3 staining is positive

**Figure 26.** a) Atypical lymphoid cells(NK/T-CELL LYMPHOMA) b) Diffusely immunoreactive with CD3C

### **5.4. Burkitts lymphoma**

#### *5.4.1. Definition*

Burkitt's lymphoma is a malignancy of B-lvmphocyte origin that represents an undifferenti‐ ated lymphoma. The tendency for jaw involvement seems to be age related: nearly 90% of 3 year-old patients have jaw lesions.

#### *5.4.2. Immunohistochemical stains*

There were statistically significant differences in the expression of CD10 (28/28 vs. 1/16), bcl-2 (3/28 vs. 11/16), MUM1 (5/28 vs. 15/16), a PI of 95. 0% or more (27/28 vs. 2/16), and combined CD10+/bcl-2-/bcl-6+ (24/28 vs. 1/16) between BLs and DLBCL-HPSSs. Of the BLs, 7 (25%) of 28 and 26 (96%) of 27 were positive for EBER and c-myc rearrangement as compared with 0 of 16 and 1 (7%) of 15 DLBCL-HPSSs, respectively as compared with 0 of 16 and 1 (7%) of 15 DLBCL-HPSSs, respectively. [17-19, 63]

c)

**Figure 27.** a) Burkitt's lymphoma. "starry-sky" appearance b) CD10 staining

## **6. Bone tumors**

The common bone tumors needing IHC are:


#### **6.1. Osteosarcoma**

#### *6.1.1. Definition*

**5.4. Burkitts lymphoma**

year-old patients have jaw lesions.

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*5.4.2. Immunohistochemical stains*

HPSSs, respectively. [17-19, 63]

**6. Bone tumors**

**•** Osteosarcoma

**•** Chondrosarcoma

**•** Ewing sarcoma

Burkitt's lymphoma is a malignancy of B-lvmphocyte origin that represents an undifferenti‐ ated lymphoma. The tendency for jaw involvement seems to be age related: nearly 90% of 3-

There were statistically significant differences in the expression of CD10 (28/28 vs. 1/16), bcl-2 (3/28 vs. 11/16), MUM1 (5/28 vs. 15/16), a PI of 95. 0% or more (27/28 vs. 2/16), and combined CD10+/bcl-2-/bcl-6+ (24/28 vs. 1/16) between BLs and DLBCL-HPSSs. Of the BLs, 7 (25%) of 28 and 26 (96%) of 27 were positive for EBER and c-myc rearrangement as compared with 0 of 16 and 1 (7%) of 15 DLBCL-HPSSs, respectively as compared with 0 of 16 and 1 (7%) of 15 DLBCL-

a) b)

**Figure 27.** a) Burkitt's lymphoma. "starry-sky" appearance b) CD10 staining

The common bone tumors needing IHC are:

*5.4.1. Definition*

Osteosarcoma is the most common nonhematopoietic primary malignant bone tumor ; it is a malignant mesenchymal tumor producing osteoid from the tumor cells (Figure 28).

#### *6.1.2. Immunohistochemical stains*

CD99 positive; rare cytokeratin and smooth muscle actin reaction. Overall, the reported specificity of immunoreactivity for osteonectin and osteocalcin is approximately 40% and 95%, respectively, for the diagnosis of a bone forming tumor. A recent promising marker for identification of osteoblastic differentiation is SATB2, a nuclear matrix protein that plays a role in osteoblast lineage commitment. α-SMA and desmin, which can lead to misdiagnosis. [63-69]

**Figure 28.** a) Osteosarcoma demonstrates irregular trabeculae of tumor osteoid arising from sarcomatous stroma. b) CD99 is positive

#### **6.2. Chondrosarcoma**

#### *6.2.1. Definition*

c)

Chondrosarcoma is a malignant tumor of bone that shows pure cartilaginous differentiation. Secondary changes that include myxoid features, ossification, and calcification may be present. (Figure 29).

#### *6.2.2. Immunohistochemical stains*

Cartilage stains S100 protein positive Mesenchymal chondrosarcoma: Sox9, CD99, and Leu7 positive Although the cartilaginous component of mesenchymal chondrosarcoma is S-100 protein positive, the small-cell component expresses CD99, CD57, and NSE therefore immu‐ nohistochemically, there may also be overlap with Ewing sarcoma. However, unlike Ewing sarcoma, MCS is nonreactive for synaptophysin and also typically does not express desmin, actin, cytokeratin, or EMA. In addition, MCS lacks *EWSR1* gene rearrangements. However, a recent study has identified a novel *HEY1-NCOA2* fusion in MCS which appears to be a consistent finding. [70, 71]

c)

**Figure 29.** a) High-grade chondrosarcoma b) with marked S100 PROTEN increase in cellularity and myxoid matrix

#### **6.3. Ewing sarcoma**

#### *6.3.1. Definition*

High-grade, primitive neuroectodermal neoplasm (Figure 30)

#### *6.3.2. Immunohistochemical stains*

Positive: FLI1 (nuclear), CD99, vimentin; rarely keratin. May react with other neural markers (NSE, synaptophysin, S100 protein, NFP, GFAP, chromogranin). [72-79]

**Figure 30.** a) Small nucleoli scant cytoplasm with mitosis b) diffuse strong membranous expression of CD99
