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Connective tissue neoplasms

Today we will talk about tumors of connective tissue that include benign and malignant *Connective tissue neoplasm will appear clinically as over growth * Connective tissue in our body are : bone , cartilages , fibrous tissue , , neurons , adipose tissue

tumors of the fibrous tissue

* it`s rare * cell of origin is fibroblast * benign tumor for the fibrous tissue is true fibroma We have 4 types of the benign tumors of the fibrous tissue ( ONLY you must know the name of it without knowing the histology of it ) (1) the peripheral odontogenic fibroma (2) fibrous histiofibroma (3) nodular fasciitis ( neoplastic like lesion ) (4) fibromatosis remember : the most common lesion of the reactive hyperplasia of connective tissue is fibroepithelial polyp ( irritation fibroma ) and it`s hypocellular and contains collagens

look to the gingival fibromatosis it is not neoplastic and the patient need incisions to allow the teeth to erupt ( THIS IS NOT the fibromatosis that we are talking about )

the fibromatosis we talked about will look like a mass which is big and aggressive and it may lucent the teeth but microscopically it is not malignant ( idon`t see hyerchromatism , mitotic figures , pleomorphism and other malignant features ) only I will see hypercellularity and to distinguish this lesion from irritation fibroma we must know that irritation fibroma is hypocellular

** so this picture is showing hypercellularity but it doesn`t show malignant features so it`s called fibromatosis ( benign tumor )

Fibrosarcoma I may give you the same clinical picture for the benign tumor but in histology I will see pleomorphism , elongated nucleus , rounded nucleus mitotic figures , hyperchromatism so I will consider it malignant tumor

** You should distinguish the irritation fibroma , the aggressive fibromatosis and the fibrosarcoma clinically and histologically

Tumors of adipose tissue

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* lipoma : benign tumor of the adipose tissue * it is usually circumscribed ( the borders are obvious ) Clinically (1) it look yellowish (2) we can also see blood vessels on the surface (3) if you cut it will floats in formalin >> depending on the density of fat Some infants and young children are presented to the clinic with ulcerated tumor-like masses of fat in the buccal mucosa which aren't actually tumors but traumatic herniation of the buccal pad of fat So if there is trauma in cheek the buccal pad of fat will herniate into the oral cavity in between muscles as a mass so this will cause herniation due to trauma WHAT is herniation ?? For the intestine to be herniated , it will protrude into the abdomen muscles in weak areas ** according to histology we can say that the lipoma is (1) Fibrolipoma: which I have a lot of collagen in association with fat (2) angiolipoma: if I have a lot of blood vessels (3) myxolipoma : if the lipoma is with loose tissue which is the myxoid tissue that have fibrils NOW how do you feel lipoma ? it is soft or compressible , if there is a lot of fibrous tissue it may be firm ,, but commonly it is soft so according to the texture of the mass I can distinguish the type of lesion that I have

**To distinguish the benign from the malignant tumor we must know that (1) in BENIGN the the cell is mature and the nucleus of the adipose cells is in the peripheral of the cell . (2) in MALIGNANT tumor the cell is immature , the nucleus is in the central and we have the malignant features .

Lipoma liposarcoma

Tumors of the vascular tissue

Hemangioma : some books consider it as true benign tumor and some said that it`s hematoma (hamartoma : is a normal tissue in it`s normal location but with abnormal excessive Amount ) So in hemangioma we have increase of the blood vessels , collection of blood vessels increase in number but in normal location Hemangioma may be present in (1) mucosa in the oral cavity (2) deep inside the muscles (3) inside the bone

(4) any where . because we have blood vessels anywhere Maybe occur in (1) children (2) young adults (3) some lesions will appear later in life * parotid gland may have hemangioma because we have blood vessels there * if we have multiple hemangiomas we should think about sturge weber syndrome Clinical presentation Blue to purple in color ( it`s not red because blood vessels are deep in the tissue or surfaced by tissue ) - Soft or comprisable ( it mean that i`m having a fluid inside this lesion , the fluid is blood ) - they blanch on pressure (get white when pressurized with a glass plate) and the color in the pressing area will become pale , however some lesions have thrombosis or calcifications and get hard and so they don't blanch - hemangioma may increase in size if bleeding , thrombosis , calcification and secondary inflammation occur inside the lesion - it can be one lobule or it can be multi lobulated
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Multilobulated hemangioma hemangioma in the in the lower lip mass and it histological picture

multilobulated tongue as a purple maybe of many years duration

- According to the size of vascular spaces we may have dilated blood spaces (you should keep in mind that the blood spaces are lined by endothelial cells unlike the aneurysmal bone cyst which is also collection of red blood cells in spaces but the spaces are not lined by endothelial cells ) - the hemangioma maybe capillary , cavernous and mixed - cavernous hemangioma : when the blood vessels are dilated - The location of the blood vessels are not superficial , they are deep in the tissue , below the epithelium , it goes down - In lymphangioma the lymphatic vessel or channels are superficial - Capillary with cavernous are called mixed

**this picture shows cellular hemangioma because I see a lot of endothelial cells , they are forming tube capillary size vessels but they are sheets of endothelial cells so we consider it cellular hemangioma not capillary hemangioma ** we use a stain called CD 34 to be sure that these cells are endothelial cells >>>> so this test is positive in endothelial cells In this picture some people will say that it is capillary hemangioma because the endothelial cells will form like capillary tube vessels so it`s cellular and in worst possibilities it chould be capillary but not cavernous or mixed **Cellular hemangioma occur commonly in young age children WE HAVE other malformation other than hemangioma like : (1) arteriovenous malformation : when the there is artery next to the vein NORMALLY : we have the artery then arteriole then capillary then veniole then vein . *but here you have thick muscular artery ( with smooth muscle wall ) next to thin walled vein whithout passing through capillary stage * in this lesion you will feel pulsation (2) malignant vascular lesion Malignant tumors of endothelial cells : (1) angiosarcoma :

**it will metastasize **the malignant cells are endothelial cells ** we will see the malignant features ( pleomorphism , hyperchromatism , hyper mitotic figure , variation in size and shape ) (2) Kaposi sarcoma : ** intraorally or in the skin ( permented patch , in sun exposed or non exposed areas ) ** it will not metastasize
We will talk about it when we talk about AIDS later on ..

Angiomatous syndromes
(1) sturge weber syndrome Here in this syndrome we will see multiple hemangiomas following the branches of the trigeminal nerve extraorally and intraorally We can see : (1) enlargement of the gingival (2) redness (3) macroglossia ( increasing the size of the tongue )

** also hemangiomas in the meninges can occur over the cerebral cortex in the same side and convulsion occur in the opposite side of the body

(2)Hereditary hemorrhagic telangiectasia:

- An autosomal disorder characterized by multiple knots of dilated malformed and fragile capillaries in skin, mucous membranes and may be the internal organs

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- Frequent nose bleeding (epistaxis) is the commonest presenting symptom

(3)Lymphangioma
** dilated lymphated channels located superficially in mucosa so you can see small bubbles in mucosa ** increase in size may occur due to inflammation or calcification

Here you can see the tongue with small lobules because of the dilated lymphatic channel underneath the epithelium .

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* here we can see empty spaces and some spaces contain lymph ** Some times in lymphangioma there will be apical location and also containing RBC >> it maybe secondary hemorrhage or bleeding at the time of operation In the presence of the RBC the location of the channel will the indication that will help us distinguishing between lymphangioma and hemangioma ** we have special stains to the endothelial lining of the lymphatic channels

Cystic hygroma:
*It is a Lymphangiomatous malformation that occur early in development of lymphatic system * Lesions are detected at birth and present as large swelling often up to 10 cm in diameter

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*They most frequently affect the head & neck region, but may extend to involve the base of the tongue, the floor of the mouth, and less commonly buccal mucosa

Tumors of the peripheral nerves

1. Nerve sheath tumors: 1. Neurofibroma - Solitary - Multiple (neurofibromatosis) 2. Shwannoma 2. Traumatic neuroma 3. Multiple mucosal neuroma NEUROFIBROMA

clinically :
I have a mass, this mass is soft (compressible) or firm??? It will be FIRM because it contain cells (Schwann cells & fibroblast). ** neurofibroma may be well defined or it may be diffuse (both clinically & microscopically) ,so sometime clinically it will be well defined ,thats mean I can determine the borders of the mass but most of the time it will be diffuse . HISTOLOGICALLY: we have 2 components , look here >> I have amass containing spindle cells as I see, I may think these are fibroblast , but if we look carefully , we will see cells with wavy nuclei (coma shape nuclei \ or dote cell like nuclei ) these cells are considered as Schwann cells mixed with other spindle cells .

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Immediately I should ask for a stain called s100 stain , which is positive for Schwann cells , and in this case the lesion will not be 100% positive coz we have a fibroblast ( not all of the cells are Schwann cells ,so we will have some positive & some negative ) . sometimes we can point a few nerve axons (u should know that the Schwann cells are not as the same as nerve axon, Schwann cells are nerve sheathe cells at periphery of the nerve, but the axon are the axon of the nerve itself!! and contain myelin inside it) so, if I ask for stain for myelin, will see occasional nerve fibers among these cells. Look at these cells (in slide 81) >> they are wavy cells and bind with coma shape nuclei. NEUROFIBROMATOSIS I In this syndrome we have a mutation in NF1 gene (tumor suppressor gene) what is the characteristic of this syndrome??? 1- multiple neurofibromas of cutanous nerves ( nerve that spreads all over the skin) if this neurofibromas are removed surgically , they show that they will carry higher tendency for malignancy transformation . 2-there will be also freckeling , and this freckeling is in the area that are not sun exposed(axillary freckeling). 3-caf-au lait spots, they have brown pigmented spot on their skin & these spots are big & have smooth borders. ((The DR asks: give me another syndrome include caf-au
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lait spot???McCeune Albright syndrome)) 4- malignant transformation 5-15% of all cases , but it will increase with recurrent surgical removal of these masses. Kind of neurofibroma that is most commonly associated is called PLEXIFORM NEUROFIBROMA so it is the most common with this syndrome, so if I have diagnosed microscopically that the pt have plexiform neurofibroma, I should write note for the clinician to examine the pt for neurofibromatosis. SCHWANNOMA Here we have a mass, its a benign the lesion mass in schwannoma mainly or almost all of tumor, its keep enlarging, and its next to the mental composed of Schwann cells . nerve. In this case the tumor arises adjacent to the nerve (for It has acharctarstic appearance example: we have the mental nerve & adjacent be parallel to it we have that there will mass that attached to the nerve itself). arrangement of the nuclei of the Usually the nerve fibers dont pass through the lesion,mean Schwann cells, thats they pass over it or they attached to it (this feature are arranged in these cells is important). parallel bundles with so its like this
palisaded nuclei. so, u will see cellular area & acellular area (I dont see this in fibroma ). if I do stain for this lesion (S100 stain) , what do u think that u will see?? 100% positivity or 50%??? Almost 100% positivity

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TRUMATIC NEUROMA we dont have a defiant pattern of traumatic neuromas for example, if the pt have an extraction & there was a cut in the mental nerve after extraction, then this nerve will give an attempt to regenerate and try to make healing, but healing will not occur, and we will see small nerves haphazardly scattered throughout the mass in addition to Schwann cells at the periphery &maybe fibroblast (scar tissue). So we have a mixture of nerves +Schwann cells+ fibroblast in haphazard organization. Clinical features: 1- painful to palpation coz it contain nerves inside it. 2-firm coz it contain cells & it may be fixed to the surrounding str 3-it is occur usually at big or large nerves such as mental nerve *** u should keep in mind that this is not neoplastic it is reactive so , neurofibroma + schwannoma >>>neoplastic traumatic neoromas >>>reactive (to cutting in the nerve)

NOW, if I saw this appearance in multiple region inside the oral cavity (this neuromas ,this histological appearance ) y3ne the pt have multiple lesion with similar diagnosis (multiple mucosal neuromas ) , I should think about syndrome called MULTIPLE ENDOCRINE NEOPLASIA TYPE IIb(MEN) . -in this type , we will have multiple mucosal neoromas , and in this case mucosal neoroumas are NOT due to cut in the nerve , coz they are appear as a component of the syndrome ( but in the traumatic neoroumas they found there duo to cutting in the nerve). -mutation in RET oncogene lead to this syndrome .

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-in this syndrome the pt has medullary thyroid carcinoma (this is the dangerous part of the syndrome). **medullary thyroid carcinoma is dangerous & fatal & diagnosed late in life. **so if u diagnosed your pt as having multiple neoromas ,u maybe the one to save the life of the pt coz he may have the thyroid gland to be removed completely (prophylactic thyroidectomy) before medullary thyroid carcinoma occur . SO, WE HAVE >> 1-multiple mucosal neoronas 2-phaecromocytoma(tumor of adrenal medulla) 3-medullary thyroid carcinoma -RET oncogene screening can be used for prophylactic detection of this pt ,if u are thinking that your pt have MEN ,then RET oncogene screening is important. GRANULAR CELL TUMOR - the cytoplasm of the cells in this lesion contain granules -it is originate from Schwann cells ,previously they thought that it is originate from skeletal muscle (they thought that it is a muscular tumor) but later on they found that this tumor originate from Schwann cells(thats mean the granular cells will stain with S100 stain). -it is a benign tumor, probably of Schwann cells. -previously , it was called myoblastoma (coz they thought that its originate from skeletal muscle ) -the best location for granular cell tumor is the TONGUE (coz it contains skeletal muscle) but it also may occurs at buccle mucosa or anywhere inside the oral cavity . -it is firm to palpation & it is attached to the overlying mucosa and the underlying tissue so that it is not well demarcated . The Histology picture:

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-in the histological picture u can see skeletal muscle fibers, and we have a sheet of cells contain granular cytoplasm, these granules are lysosome. -we have abundant or plenty cytoblast (granular cells) ,these cells are not small,they are big cells with granules ,and they interpreting with skeletal muscle fibers, for this reason , they used to be called myoblastoma (coz they thought it arise from skeletal muscle due to this appearance). PSUEDO-EPITHELIOMATOUS HYPERPLASIA -the surface epithelium is hyperplasic but it will give u an indication that it is as a malignant since it is invading the underlying tissue(this feature seen in some lesion like capillary(sorry I cant hear) hyperplasia ,granular cell tumor ,& later on we will talk about deep fungal infection ( when we talk about the candidosis & deep fungal inf) SO, -it is actually hyperplasia, but it will give u an indication that it is a malignant. _there is an intimate contact with the surface & the underlying structure for this reason the granular cell tumor is not movable (fixed to the surrounding structure, but it is a benign). NOW, based on these features, does u think that we need an aggressive treatment???Wide surgical excision (for granule
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cell tumor)??? Actually NO despite the fact that it is intermingling the skeletal muscle & it is ill-defined but it doesnt need an aggressive treatment, they found that it will not recur after conservative surgical treatment.

TUMORS OF the MUSCLE

you should know the terminology: *benign tumors of smooth muscle are called >>leiomyoma *malignant tumors of smoothe muscle are called >>leiomyosarcoma *benign tumor of skeletal muscle is called >>rhabdomyoma *malignant tumors of skeletal muscle are called >>rabdomyosarcoma -leiomyoma sometimes, it is vascular, it is appearing like hemangiomawhy??? Coz the smooth muscle occurs in association of blood vessel so some times leiomyoma maybe vascular. LYMPHOMA types of lymphoma: 1-hodgkins lymphoma 2-non-hogdkins lymphoma what is the lymphoma that start in the lymph node?? Hodgkins lymphoma also Hodgkins lymphoma prefer to occur in the cervical lymph node **non-Hodgkins lymphoma usually start in extra nodal location and then it is metastasis later on or spread and reach the lymph node.
(EBV may be linked to the most of the types of lymphomas , coz the latency period of EBvirus is inside the lymphocyte especially B cells, so they found that it is correlated with lymphoma ) 19

1-HODGKINS LYMPHOMA -30% of all lymphoma

-it is prefer young age group -it is prefer cervical lymph node -they found that EBV may be linked to Hodgkins lymphoma . -genetic favor may play role, coz they found that in twins ,if one child have Hodgkins lymphoma there will be a high chance that the another childe to get lymphoma. -prognosis depends on staging & grading WHAT IS THE DEFFERANCE?? Staging >>depend on clinical feature grading >>depend on histological feature.

Look to the cervical chain ,look how the lymph node show diffuse enlargement ,and they are linked ( ) u cant move them , and the texture is rubbery and firm ,it is not soft like in reactive lymph node ( when u have tonsillitis ,u have a lymph node enlargement but the texture is soft and the lymph node usually tender (painful )) but in this case NO, they are rubbery ,firm ,& attached to each others like one chain .

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These cells are called REED- STERNBERG cells; it is the malignant components in the Hodgkins lymphoma. These cells are: 1-big cells 2-with 2 nuclei 3-or one big cell with one nucleus in pop-corn appearance. The cells that surrounding these reed-Sternberg cells are lymphocytes and they are not malignant. SO, what does u think is better for the pt, to have high number of reed-Sternberg cells??Y3ne to have lymphocytes predominant or reed-Sternberg predominant??? Lymphocytes predominate.
SO, as the numbers of lymphocytes decrease, then the prognosis will be bad for the pt

For this reason in the histopathological type the lymphocytes predominate has the best prognosis then mixed cellularity then nodular sclerosis then lymphocyte depletion? 2-NON-HODGKINS LYMPHOMA
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-it starts extra nodally . **may occur in the mucosa then it will be called MALT lymphoma (mucosa associated lymphoid tissue lymphoma). **it may occur in the stomach in association with H-pylori (u know that H pylori infection associated with lymphoma, so anyone have H pylori infection in the stomach, he should get a treatment, since it may coz lymphoma). **it may occur inside the salivary gland itself especially in sjogren syndrome . **it may occur inside the bone **in may occur in association with AIDS pt -cell types: mainly they are B-cell types, but T-cell or NK cells also may present.

here we have inside the oral cavity an aggressive mass with bleeding , it is destroying the teeth ,there is also ulceration , it is ugly , rapidly growing , we should think about malignant process ,if we are not sure , we take abiopsy ,send it to the lab,and then in the lab the histopathlogist will see a sheet of small cells ( lymphocyte ) but there will be hyperchromatisim & mitosis in some of them , and we will order especial stain then we will tell the clinician that we are having here B-cell type lymphoma ( if we have, for example, CD20 positive cells ).

BURKITS LYMPHOMA
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it is endemic & sporadic (endemic means it is occur in certain georafephic location, sporadic .) - in certain geographic location like Africa ,when there is EBV and malaria together then the immune system will altered ,then the pt will have burkits lymphoma . -the clinical presentation for endemic burkits lymphoma is differ from sporadic **in the endemic >> it will start in the jaws **in the sporadic >>it will start in the abdomen SO in the endemic burkits lymphoma the pt will have jaw lesion then spread will occur . -there is a specific chromosomal translocation that it is 8,14 which will lead to c-myc activation . -the cells in burkits lymphoma >> B-cells histologically we will see something called starry sky appearance ,u will see a blue areas and stars, the stars are non-neoplastic component which are the macrophages (u know that the macrophages are big cells & have abundant cytoplasm and the color of the cytoplasm is pale compared to the nucleus , so it appears pale , and look to the cytoplasm it is containing lymphocyte coz the macrophages trying to engulf the malignant cells in order to kill the malignant cells). NK\T CELLS LYMPHOMA -it is called angiocentric T-cell lymphoma. -it is occurring around the blood vessel. -it is occurring in the mid line. -it used to be called lethal midline granoloma (coz it coz death if it occurs in the palate) -if it occur in the palate, it will coz perforation of the palate, it will reach the nasal cavity. -the cells either T-cell or NK. -they found that EB virus in these cells, and it is also present in most of other types of lymphoma.

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Done by : sondos harbieh and haya al momani

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