Soft Tissue and Bone 2022

Soft Tissue Lesions Dr Rachel Carey

Exam Tips • Lots of different entities – don’t try to learn them all • Can you work out the type of differentiation? (from morphology/immuno) • Any buzz words?

• Learn genetic mutations

Spindle Cell Tumours • OTHER • Carcinoma • Melanoma

• • • • • • • •

Adipocytic tumours Fibroblastic/Myofibroblastic tumours Fibrohistiocytic Tumors Adipocytic tumours Vascular/Perivascular tumours Muscle tumours Nerve/Nerve sheath tumours Tumours of uncertain differentiation

MCQ 2 A 40 year old man with a plaque like lesion on the chest. Histology shows a dermal cellular spindle cell lesion with a storiform pattern and stains positively for CD34 and negative for CD31, EMA, SMA, Desmin and S100. No epidermal attachment is seen.

The most likely diagnosis is: a. Spindle cell carcinoma b. Kaposi’s sarcoma c. Dermatofibrosarcoma Protuberans d. Malignant melanoma e. Angiosarcoma

MCQ 2 A 40 year old man with a plaque like lesion on the chest. Histology shows a dermal cellular spindle cell lesion with a storiform pattern and stains positively for CD34 and negative for CD31, EMA, SMA, Desmin and S100. No epidermal attachment is seen.

The most likely diagnosis is: a. Spindle cell carcinoma b. Kaposi’s sarcoma c. Dermatofibrosarcoma Protuberans d. Malignant melanoma e. Angiosarcoma

FIBROBLASTIC/MYOFIBROBLASTIC TUMOURS

Fibroblastic/Myofibroblastic Spindle Cell Tumors • • • • • • • • • • • •

Nodular Fasciitis Fibromatosis Elastofibroma Dermatofibrosarcoma Protuberans Pallisaded myofibroblastoma Low grade myofibroblastic tumour Solitary fibrous tumour Myxoinflammatory myofibroblastic sarcoma Inflammatory myofibroblastic tumour Fibrosarcoma Myxofibrosarcoma Sclerosing epithelioid fibrosarcoma

DFSP (Dermatofibrosarcoma Protuberans)

• • • •

Slow growing locally aggressive tumour 3rd and 4th decade Local recurrence 20 – 50 % Metastasis exceedingly rare – less than 0.3%

• Over 95% of DFSP tumors have the chromosomal translocation t(17;22). The translocation fuses the collagen gene (COL1A1) with the platelet-derived growth factor gene.

Macro • Trunk and proximal extremities • Multinodular cutaneous mass several cm in diameter

Micro • • • • •

In dermis and subcutis High cellularity Spindle cells in storiform arrangement May see mild pleomorphism and a few mitoses May infiltrate the subcutis in a “honeycomb” pattern

CD34

D2-40 and Factor XIIIa negative

DFSP Variants • Bednar tumour - pigmented; • Fibrosarcomatous – recurrence 70%; metastasis 20%, loss of CD34; • Myoid; Myxoid; Granular Cell; Atrophic; Sclerosing; Palisaded; GCF;

MCQ 3 • 23 year old man presents with a rapidly growing soft tissue mass on the arm. Histology shows a cellular lesion with plump fibroblast and myofibroblast-like cells with oedema and red cell extravasation. Mitoses are seen but no atypical forms or nuclear pleomorphism. What is the most likely diagnosis?

• • • • •

A. DFSP B. MPNST C. Sarcomatoid carcinoma D. Nodular fasciitis E. Angiosarcoma

MCQ 3 • 23 year old man presents with a rapidly growing soft tissue mass on the arm. Histology shows a cellular lesion with plump fibroblast and myofibroblast-like cells with oedema and red cell extravasation. Mitoses are seen but no atypical forms or nuclear pleomorphism. What is the most likely diagnosis?

• • • • •

A. DFSP B. MPNST C. Sarcomatoid carcinoma D. Nodular fasciitis E. Angiosarcoma

Nodular fasciitis • Used to be classed as a reactive process, but now thought to be a benign neoplastic lesion • Self-limiting, proper diagnosis is essential to avoid unnecessary aggressive treatment • A really good sarcoma mimic • USP6 gene rearrangement

Macro • Solitary painless, rapidly growing nodule over several weeks duration • Extremities and trunk , but 10 – 20% of cases arise in the head and neck region

Micro • Cellular, spindle cell lesion (fibroblasts and myofibroblasts) • Cells dispersed in myxoid matrix with feathery/tissue culture apperance • Variable numbers of lymphocytes and hemorrhage • Variable collagenization, older lesions sometimes showing keloidal change • SMA positive, CD34 negative

Solitary fibrous tumour (SFT) • • • • • • •

Usually benign but some show malignant behaviour Can occur ANYWHERE but likes pleura/pericardium Differential for spindle mesothelioma Patternless growth pattern Thick collagen Staghorn vessels Stat6+

Fibrosarcoma • True/ pure adult fibrosarcomas exceptionally rare outside the setting of transformed dermatofibrosarcoma protuberans • Classic herringbone pattern - parallel sheets of cells arranged in intertwining whorls • Well-differentiated forms have multiple plump fibroblasts with deeply staining nuclei in a rich collagen background

(SO CALLED) FIBROHISTIOCYTIC TUMOURS

Fibrohistiocytic Spindle Cell Tumors • Fibrous Histiocytoma/Dermatofibroma • Tenosynovial Giant Cell Tumour • Giant Cell Tumour of Soft Tissue

Benign Fibrous Histiocytoma • Also called dermatofibroma, cutaneous fibrous histiocytoma • Very common (3% population) • Middle aged females, extremities • Significant association with previous trauma • Eruptive lesions in the context of immunosuppression, HIV infection and HAART • ?reactive or neoplastic – significant association with previous trauma

Macro • Button-like, firm, raised nodule • Often dark brown (due to haemosiderin) – may be mistaken for a melanocytic lesion

Micro • Lens shaped with Grenz zone • Well defined but not encapsulated • 3 components • Spindle cells • Bland • Often storiform or patternless arrangement

• Hyalinized collagen • Can look trapped at peripheries

• Macrophages • Foamy or haemosiderin-laden • Can form touton giant cells

• Can induce changes in overlying epidermis • • • •

Atrophy Acanthosis Basaloid proliferation Sebaceous induction

Immunohistochemistry Factor XIIIa expression

CD34 expression

Discussion- DF variants • Numerous variants including: Cellular; Atypical; Aneurysmal; Clear Cell; Halo; Granular; Muxoid; Keloidal; ‘Monster cell’; Lipidised; Angiomatous • Uncertain significance

Cellular variant • • • • • • •

Young or middle-aged adults Wide anatomic distribution 26% recurred locally Commonly fascicular growth pattern Moderate mitotic rate Extension into subcutis (33%) Foci of central necrosis (12%)

Atypical 'pseudosarcomatous' variant Kaddu S, McMenamin ME, Fletcher CD Am J Surg Pathol. 2002 Jan;26(1):35-46

        

59 cases Mainly extremities, age range 5-79 years Proliferation of pleomorphic, plump, spindle cells Background classic DF Mitotic figures 1 -15 / 10 hpf Atypical mitoses (n=20) Geographic necrosis (n=7) Local recurrences (n=3) Distant metastases (n=2)

Giant cell tumor of tendon sheath • Female predominance • 30-50 years • CSF1 mutation (a chemoattractant, meaning macrophages infiltrate the tumour in large numbers)

Macro • Hand most commonly affected • Feet, ankles and knees less often involved • Firm nodule with lobulated surface

Micro • • • • • •

Sharply circumscribed with mature collagenous pseudocapsule Dense fibrous stroma generally present Polygonal cells with eosinophilic cytoplasm and vesicular nuclei Multinucleate giant cells Haemosiderin-laden histiocytes, xanthoma cells and inflammatory cells Foci of hemorrhage commonly seen

ADIPOCYTIC TUMOURS

Adipocytic Tumours • • • • •

Lipoma Angiolipoma Spindle Cell Lipoma Hibernoma Atypical lipomatous tumour/well differentiated liposarcoma • Liposarcoma

Spindle cell lipoma • Mainly middle aged males (45 – 60 years old) • Subcutaneous tissue of the posterior neck, shoulder, back • Also can present in dermis • Mature fat cells, bland spindled cells set in a myxoid matrix • Characteristic thick bands of birefringent collagen – “ropey collagen” • Spindle cells CD34 positive.

Spindle cell lipoma

Liposarcoma • Atypical lipomatous tumour/Welldifferentiated liposarcoma • Myxoid • Round cell • De-Differentiated • Lipoblasts!

MCQ 1 An 85 year old man undergoes a skin and soft tissue excision biopsy for an illdefined nodule on the posterior neck measuring 4cm in diameter: Histologically the epidermis is atrophic but otherwise normal. The sun-damaged dermis shows a pleomorphic epithelioid cells with many mitotic figures which extends into the subcutaneous tissue. Focal vascoformative pattern is seen.

Immunohistochemically, the tumour cells are positive for CD31, CD34 and focally for MNF116. It is negative for S100, HHV8, smooth muscle actin and desmin.

•

The most likely diagnosis is: a. Spindle cell carcinoma b. Kaposi’s sarcoma c. Atypical fibroxanthoma d. Malignant melanoma e. Angiosarcoma

MCQ 1 An 85 year old man undergoes a skin and soft tissue excision biopsy for an illdefined nodule on the posterior neck measuring 4cm in diameter: Histologically the epidermis is atrophic but otherwise normal. The sun-damaged dermis shows a pleomorphic epithelioid cells with many mitotic figures which extends into the subcutaneous tissue. Focal vascoformative pattern is seen.

Immunohistochemically, the tumour cells are positive for CD31, CD34 and focally for MNF116. It is negative for S100, HHV8, smooth muscle actin and desmin.

•

The most likely diagnosis is: a. Spindle cell carcinoma b. Kaposi’s sarcoma c. Atypical fibroxanthoma d. Malignant melanoma e. Angiosarcoma

VASCULAR TUMOURS

Vascular Tumours • • • • • • • •

Pyogenic granuloma Haemangiomas Angiokeratoma Haemangioendotheliomas Kaposi’s Sarcoma Atypical vascular lesion Epithelioid haemangioendothelioma Angiosarcoma

Kaposi’s Sarcoma Four epidemiological varieties described: Classic KS: • Indolent disease; Affects elderly men • Mediterranean region, or of Eastern European descent, Jews Endemic KS • Middle-aged males, mainly from sub-Saharan Africa; Generally indolent • Infiltrates the skin extensively, especially lower limbs; Visceral or nodal disease in children, aggressive behavior Transplant Related KS • Especially when associated with cyclosporine Epidemic KS • An aggressive disease in HIV/AIDS patients

Kaposi’s Sarcoma • • • • • • •

3 Clinical stages: patch, plaque and nodular Dermal but may extend into subcutis (usually plaque and nodular lesions) Proliferation of numerous irregular vascular spaces Vascular channels parallel to the epidermis May show ‘Promontory’ sign Extravasated red blood cells and hemosiderin Histiocytes, lymphocytes and plasma cells

• • •

Patch stage: features may be subtle showing plasma cells associated with increase in slit-like vascular spaces in the upper dermis.

Plaque stage: eosinophilic spindle cells more prominent Nodular stage: multi-nodular; eosinophilic spindle cells in a fascicular pattern

• •

CD34 (diffuse) and CD31 (focal) positivity Human Herpes-virus 8 positive (99% cases)

Cutaneous angiosarcoma • Different clinical setting (head and neck of the elderly (sun); post-irradiation, background of lymphoedema) • Post RT = MYC positive • Anastomosing vascular channels with plumo endothelial cells • May form intracytoplasmic lumina • Cytologic atypia, Mitoses • Can mimic KS and in difficult cases immunohistochemistry will help make the distinction (Angiosarcoma: CD31 diffuse staining, HHV8 negative)

MUSCLE TUMOURS

Tumors of Muscle • Leiomyoma • Leiomyosarcoma • Rhabdomyosarcoma – Embryonal – Alveolar – Spindle – Pleomorphic

Leiomyoma  Can occur in various places:      

Fibroid = leiomyoma from uterine smooth muscle Cutaneous leiomyoma = from erector pili muscles in skin Genital Leiomyoma = arising in scrotum or vulva Subcutaneous leiomyoma = arising from BV SM in subcutis GI leiomyoma = in bowel wall Deep leiomyoma = in pelvis or retroperitoneum. Usually of vascular origin

• Uniform interlacing bundles of cells with elongated cells with brightly eosinophilic cytoplasm and blunt ended nuclei.

• Immuno’ – SMA, Desmin, h-caldesmon

Leiomyosarcoma • Account for 10-20% of soft tissue sarcomas • Can be superficial (skin) = better prognosis • Or Deep (retroperitoneum, GI tract etc) = worse prognosis • Same as above but atypia, mitoses, necrosis

Rhabdomyosarcoma • Most common sarcoma of childhood/adolescence • Small, round, blue cell tumour! Containing rhabdomyoblasts • Embryonal = head and neck or genitourinary.

(Botyroid subtype = classically in wall of vagina) • Alveolar = Extremities and head and neck, more primitive, alveolar pattern. Worse prognosis

Rhabdomyosarcoma

Schwannian/Neural Tumors • • • •

Traumatic neuroma Neurofibromas Schwannoma (Neurilemmoma) MPNST

Traumatic Neuroma • Peripheral hyperplastic response to peripheral nerve injury • Any age, any site • Histopathology: • Variably defined but unencapsulated mass of axons and Schwann cells embedded in scar tissue

Neurofibroma • Tumours of peripheral nerves composed of a mixture of cell types: o o o o

Schwann cells Fibroblasts Perineural cells Axons

• 90% sporadic, 10% NF1 associated • If multiple – think NF1

Micro • Well defined but unencapsulated dermal or subcutaneous nodule • Loosely arranged spindle cells with wavy nuclei, fibroblasts and mast cells in collagenous stroma • Often called “shredded carrot” collagen • Delicate fascicles • Minimal nuclear pleomorphism  Positive for… o S100 (schwann cells) o CD34 (endoneural cells) o Neurofilament (axons) o EMA (perineural cells)

Schwannoma • Pure tumour of Schwann cells • Can arise around any nerve • This tumour consists of plump spindle cells showing a marked tendency to palisade.

• Antoni A = more cellular, palisades, verocay bodies • Antoni B = looser, more myxoid, hyalinized blood vessels

Schwannoma

Neurofibromatosis • • • • •

Neurocutaneous syndromes: NF1 NF2 Tuberous sclerosis Von Hippel Lindau Syndrome

Malignant Peripheral Nerve Sheath Tumor (MPNST) • Rare tumor; often occur in patients with neurofibromatosis 1 • A sarcoma is defined as a MPNST when at least one of the following criteria is met: • Lesion arises from a peripheral nerve • Lesion arises from a preexisting benign nerve sheath tumor (usually neurofibroma, rarely schwannoma) • It demonstrates Schwann cell differentiation on histologic examination

• Most often in adults

Malignant Peripheral Nerve Sheath Tumor (MPNST) • Anatomical distribution wide • Spindled-cells with very irregular contours to rounded or fusiform cells • Marbled appearance, may see tactoid bodies resembling Meissner’s corpuscles • Nuclear palisading seen in less than 10% of cases & even then, only focally • Features suggestive of malignancy include invasion of surrounding tissues, invasion of vascular structures, nuclear pleomorphism, necrosis, & mitotic activity.

• Characteristic perivascular condensation of tumor cells is a useful diagnostic feature • 80-85% of MPNSTs are spindle cell tumors with a fascicular growth pattern similar to a fibrosarcoma

Malignant Peripheral Nerve Sheath Tumor (MPNST)

TUMOURS OF UNCERTAIN DIFFERENTIATION

Tumours of Uncertain Differentiation • • • • • • • •

Intramuscular myxoma Atypical fibroxanthoma (AFX) Undifferentiated pleomorphic sarcoma Synovial sarcoma Epithelioid sarcoma Alveolar soft part sarcoma Clear cell sarcoma Desmoplastic small round cell tumour

AFX • Coined by Helwig for a cutaneous tumour with marked cellular pleomorphism, yet with a course that is benign.

• View modified in view of rare reports of metastases • Solitary, head and neck of elderly • Classify as undifferentiated sarcoma if… o Size >20mm o Substantial invasion of the subcutis or beyond (so can’t give definitive diagnosis on shallow biopsies) o Perineural/lymphovascular invasion o Necrosis

Immunohistochemistry Negative ? CD10 not specific

Synovial Sarcoma • Previously thought to recapitulate synovium – but actually cell of origin unclear • Most common 20s-40s • Majority have t(X,18) SS18-SSX1 translocation • Mostly seen in deep soft tissues of lower extremities (around joints)

Micro • Can be monophasic or biphasic • Epithelial and mesenchymal areas • High NC ratio and little stroma (look very dark) • Immuno • Cytokeratin/EMA+ • TLE1+ (new marker) • BCL2, CD56, CD99+

Micro

Others • Alveolar soft part sarcoma • Alveolar, nested appearance • ASPSCR1-TFE3 fusion gene • Eosinophilic/clear cells • Epithelioid Sarcoma • Partial or complete epithelioid morphology • INI-1 loss • CK AND CD34+ • Clear cell sarcoma • The soft tissue melanoma • Contains iron and melanin • EWSR1-CREB translocation

EMQ A Question 1 A. B. C. D. E. F. G. H. I. J. K. L. M. N.

Pyogenic granuloma Synovial sarcoma Epithelioid sarcoma Ewing’s Sarcoma Giant cell tumour of tendon sheath Xanthoma Epithelioid haemangioma Schwannoma Neurofibroma Angiolipoma Spindle cell lipoma Elastofibroma Solitary fibrous tumour Nodular fasciitis

A 35 year old man with nodule on the arm. Dermal lesion which is encapsulated and has S100 spindle cells in loose myxoid stroma and more hypercellular areas.

Palisading of nuclei is seen.

EMQ A Question 1 A. B. C. D. E. F. G. H. I. J. K. L. M. N.

Pyogenic granuloma Synovial sarcoma Epithelioid sarcoma Ewing’s Sarcoma Giant cell tumour of tendon sheath Xanthoma Epithelioid haemangioma Schwannoma Neurofibroma Angiolipoma Spindle cell lipoma Elastofibroma Solitary fibrous tumour Nodular fasciitis

A 35 year old man with nodule on the arm. Dermal lesion which is encapsulated and has S100 spindle cells in loose myxoid stroma and more hypercellular areas.

Palisading of nuclei is seen.

EMQ A Question 2 A. B. C. D. E. F. G. H. I. J. K. L. M. N.

Pyogenic granuloma Synovial sarcoma Epithelioid sarcoma Ewing’s Sarcoma Giant cell tumour of tendon sheath Xanthoma Epithelioid haemangioma Schwannoma Neurofibroma Angiolipoma Spindle cell lipoma Elastofibroma Solitary fibrous tumour Nodular fasciitis

A 44 year old builder with a nodule on the back of the neck. The nodule has spindle cell areas, ropey collagen and fat. There is no atypia and the tumour is CD34 positive.

EMQ A Question 2 A. B. C. D. E. F. G. H. I. J. K. L. M. N.

Pyogenic granuloma Synovial sarcoma Epithelioid sarcoma Ewing’s Sarcoma Giant cell tumour of tendon sheath Xanthoma Epithelioid haemangioma Schwannoma Neurofibroma Angiolipoma Spindle cell lipoma Elastofibroma Solitary fibrous tumour Nodular fasciitis

A 44 year old builder with a nodule on the back of the neck. The nodule has spindle cell areas, ropey collagen and fat. There is no atypia and the tumour is CD34 positive.

EMQ A Question 3 A. B. C. D. E. F. G. H. I. J. K. L. M. N.

Pyogenic granuloma Synovial sarcoma Epithelioid sarcoma Ewing’s Sarcoma Giant cell tumour of tendon sheath Xanthoma Epithelioid haemangioma Schwannoma Neurofibroma Angiolipoma Spindle cell lipoma Elastofibroma Solitary fibrous tumour Nodular fasciitis

A 27 year old man presents with a nodule on the foot. The tumour is epithelioid, malignant with central areas of necrosis and is EMA +, CD34 + and AE1/AE3. S100 negative.

EMQ A Question 3 A. B. C. D. E. F. G. H. I. J. K. L. M. N.

Pyogenic granuloma Synovial sarcoma Epithelioid sarcoma Ewing’s Sarcoma Giant cell tumour of tendon sheath Xanthoma Epithelioid haemangioma Schwannoma Neurofibroma Angiolipoma Spindle cell lipoma Elastofibroma Solitary fibrous tumour Nodular fasciitis

A 27 year old man presents with a nodule on the foot. The tumour is epithelioid, malignant with central areas of necrosis and is EMA +, CD34 + and AE1/AE3. S100 negative.

EMQ A Question 4 A. B. C. D. E. F. G. H. I. J. K. L. M. N.

Pyogenic granuloma Synovial sarcoma Epithelioid sarcoma Ewing’s Sarcoma Giant cell tumour of tendon sheath Xanthoma Epithelioid haemangioma Schwannoma Neurofibroma Angiolipoma Spindle cell lipoma Elastofibroma Solitary fibrous tumour Nodular fasciitis

32 year old female with papules around the eye.

Histology shows bland foamy cells in the dermis.

EMQ A Question 4 A. B. C. D. E. F. G. H. I. J. K. L. M. N.

Pyogenic granuloma Synovial sarcoma Epithelioid sarcoma Ewing’s Sarcoma Giant cell tumour of tendon sheath Xanthoma Epithelioid haemangioma Schwannoma Neurofibroma Angiolipoma Spindle cell lipoma Elastofibroma Solitary fibrous tumour Nodular fasciitis

32 year old female with papules around the eye.

Histology shows bland foamy cells in the dermis.

EMQ A Question 5 A. B. C. D. E. F. G. H. I. J. K. L. M. N.

Pyogenic granuloma Synovial sarcoma Epithelioid sarcoma Ewing’s Sarcoma Giant cell tumour of tendon sheath Xanthoma Epithelioid haemangioma Schwannoma Neurofibroma Angiolipoma Spindle cell lipoma Elastofibroma Solitary fibrous tumour Nodular fasciitis

31 year old male with a mass around the knee. Histology shows a biphasic tumour with spindle cells and epithelioid cells. Cytogenetics shows t(x:18) translocation and radiology confirms pulmonary deposits.

EMQ A Question 5 A. B. C. D. E. F. G. H. I. J. K. L. M. N.

Pyogenic granuloma Synovial sarcoma Epithelioid sarcoma Ewing’s Sarcoma Giant cell tumour of tendon sheath Xanthoma Epithelioid haemangioma Schwannoma Neurofibroma Angiolipoma Spindle cell lipoma Elastofibroma Solitary fibrous tumour Nodular fasciitis

31 year old male with a mass around the knee. Histology shows a biphasic tumour with spindle cells and epithelioid cells. Cytogenetics shows t(x:18) translocation and radiology confirms pulmonary deposits.

Differential diagnosis – Spindle cell tumours of skin • • • • • • •

Spindle cell SCC – CK + Desmoplastic Melanoma – HMB 45, S100 Dermatofibroma - D2-40+ (podoplanin), factor XIIIa+, CD34DFSP - CD 34 +, D240 and factor XIIIa Leiomyosarcoma – SMA, DESMIN, CK +/AFX – CD10 maybe +, everything MPNST (peripheral nerve sheath tumour) – S100 +/-, CD34 +/• Kaposi Sarcoma – CD34 +, HHSV8 +, CD31• Angiosarcoma - CD31+, CD31 +, CK +/-

Differential diagnosis – Small round blue • • • • • • •

Desmoplastic small round blue cell tumour Ewing’s sarcoma/PNETs Acute leukaaemia Neuroblastoma Rhabdomyosarcoma Wilm’s tumour Melanoma

Cytogenetics- Learn!

Ewing’s/PNET Desmoplastic small round cell tumour

Mutation T(11,22) – and others T(11,22)

Gene EWSR1-FLI1 – and others EWSR1-WT1

Clear Cell Sarcoma Myxoid/Round cell liposarcoma Epithelioid Haemangioendothelioma

T(12,22) T(12,16) T(1,3)

EWSR1-ATF1/EWSR1-CREB1 EWSR1-DDIT3 (MDM2) EWSR1-WT1

Dermatofibrosarcoma Protuberans

T(17,22)

COL1A1-PDGFB (Alpha collagen and PDGF fusion)

Alveolar soft part sarcoma Synovial Sarcoma Epithelioid Sarcoma Malignant rhabdoid tumour Inflammatory myofibroblastic tumour

T(x,17) T(x,18) 22q abnormalities 22q deletion 2p23 rearrangement

ASPL-TFE3 SS18-SSX1 INI1 inactivation INI1 inactivation ALK fusion with various genes

Alveolar rhabdomyosarcoma Endometrial stromal sarcoma Chondrosarcoma Spindle cell haemangioma Giant cell tumour of tendon sheath Nodular Faciitis Deep seated fibromatosis Comgential/infantile fibrosarcoma (also secretory breast cancer, mesoblastic nephroma)

T(1,13) T(7,17) IDH1/IDH2 IDH1/IDH2 CSF1 USP6 CTNNB1

PAX7-FKHR/PAX3-FOXO1 JAZF1-JJAZ1

Intramuscular Myxoma CIC-DUX4 Sarcoma

GNAS T(4,19)

B-catenin ETV6-NTRK3

Buzz words- Learn!

• • • • • • • • • • • • • • • •

DFSP = storiform, honeycombing SFT = patternless pattern, staghorn vessels Palisaded myofibroblastoma = amianthoid fibres Fibrosarcoma = herringbone Spindle cell lipoma = ropey collagen Pleomorphic lipoma = floret cells Dermatofibroma = grenz zone, touton giant cells Liposarcoma/ALT = lipoblasts Schwannoma = Antoni A+B, Verocay bodies Neurofibroma = shredded carrot collagen MPNST = tactoid bodies, perivascular aggregates Leiomyoma = elongated “cigar” nuclei Botyroid rhabdomyosarcoma = cambium layer Pyogenic granuloma = collarette, lobules Kaposis = promontory sign Alveolar soft part sarcoma = needle-like inclusions

DISEASES OF BONES AND JOINTS

Diseases of bone Metabolic bone diseases Osteoporosis Osteomalacia Trauma Fracture Infection Osteomyelitis Tumours Metastases Haematological Primary

Osteoporosis

• Reduced number and size of bone trabeculae • Eventually see large holes in trabecular bone • Thinning of cortical bone

• Trabeculae appear normal in size and shape • But only central core is actually mineralized (outer portions are just collagen)

Osteomalacia

Vitamin D deficiency Kidney failure Liver failure Skin = Vit D precursors Active Vit D = Liver

Kidney

absorption of Ca2+ from bowel

Fracture healing Rapid repair; Starts immediately;

Haemorrhage New lamellar Bone

Fibroblast ingrowth (wound healing) Endochondral ossification

Cartilage

De novo woven bone

Bone tumours Most common Metastasis Breast Kidney Bronchus Next most common Haematological Myeloma Leukaemia Rare Primary bone tumours Named after type of matrix e.g. Osteoblastoma Malignant ones metastasise to lungs

TUMOURS OF BONE

TUMOURS OF BONE • Osteoid Osteoma • Osteoblastoma • Osteochondroma • Osteosarcoma (periosteal and parosteal)

BENIGN

• Osteoid Osteoma • Painful!

• Young people • Radiology = central osteolytic nidus with surrounding sclerotic rim of bone • Mass of partially mineralised osteoid • Osteoblastoma • Very similar to above, more osteoclasts • Osteochondroma • Most common bone tumour • Stalk growing away from growth plate • Cap of cartilage, underlying bone

•

MALIGNANT Periosteal Osteosarcoma • • • •

Children/adolescents Very aggressive Typically metaphysis of long bones Radiology = motheaten, onion skin, sunray appearance, destroys normal bone • Pleomorphic cells, irregular osteoid • Parosteal Osteosarcoma • Rare subtype • Slightly older age group • Less aggressive • MDM2 • Arises on cortical surface • Well formed trabecular bone with interweaving spindle cells

TUMOURS OF CARTILAGE

TUMOURS OF CARTILAGE • Chondroma • Chondroblastoma • Chondromyxoid Fibroma • Chondrosarcoma

CHONDROSARCOMA • Tumour of middle aged/elderly • IDH1 and IDH2 mutations • Subtypes • Conventional • Mesenchymal (younger, small cell component) • Clear cell • Periosteal • De-differentiated • Radiology = poorly defined, expanding bone

OTHERS

OTHER TUMOURS • Round Cell • Eosinophilic granuloma • Ewing’s • Giant Cell • Aneurysmal bone cysts • Giant cell tumour of bone • Brown’s Tumour • Other • Chordoma • Mets • Haem tumours

EWING’S • • • •

A type of PNET Young people, bad prognosis A small, round blue cell tumour 85% have EWSR1-FLI1 mutation

• “Ewing’s like sarcoma” – until molecular testing done • CIC-DUX 4 sarcoma • BCOR sarcoma

• Differential = other SRBCTs

GIANT CELL TUMOUR OF BONE • Benign tumour but can be locally aggressive (1% malignant) • Younger age group • Imaging = lytic lesion with soap bubble appearance.

• Neoplastic mononuclear cells with admixed giant cells • Differential = Brown’s tumour of bone (associated with hyperparathyroidism)

Options a. Telangiectatic osteosarcoma b. Osteoblastoma c. Giant cell tumour d. Chondrosarcoma e. Osteochondroma f. Periosteal osteosarcoma g. Adamantinoma of the bone h. Aneurismal cyst i. Simple cyst j. Fibrous dysplasia k. Parosteal osteosarcoma l. Conventional osteosarcoma m. Mesenchymal chondrosarcoma n. Ewing’s sarcoma o. Chordoma p. Osteoid osteoma •

EMQ B Question 1 A 19-year-old male presents with a jaw tumour, the microscopy of which, shows differentiated cartilage and a distinctive small cell component. In areas, the tumour is reminiscent of haemangiopericytoma.

Options a. Telangiectatic osteosarcoma b. Osteoblastoma c. Giant cell tumour d. Chondrosarcoma e. Osteochondroma f. Periosteal osteosarcoma g. Adamantinoma of the bone h. Aneurismal cyst i. Simple cyst j. Fibrous dysplasia k. Parosteal osteosarcoma l. Conventional osteosarcoma m. Mesenchymal chondrosarcoma n. Ewing’s sarcoma o. Chordoma p. Osteoid osteoma •

EMQ B Question 1 A 19-year-old male presents with a jaw tumour, the microscopy of which, shows differentiated cartilage and a distinctive small cell component. In areas, the tumour is reminiscent of haemangiopericytoma.

Options a. Telangiectatic osteosarcoma b. Osteoblastoma c. Giant cell tumour d. Chondrosarcoma e. Osteochondroma f. Periosteal osteosarcoma g. Adamantinoma of the bone h. Aneurismal cyst i. Simple cyst j. Fibrous dysplasia k. Parosteal osteosarcoma l. Conventional osteosarcoma m. Mesenchymal chondrosarcoma n. Ewing’s sarcoma o. Chordoma p. Osteoid osteoma

EMQ B Question 2 A child presents with cranial nerve deficits and a lobulated soft tumour is excised from the cervical vertebrae. The tumour is S100 and EMA positive.

Options a. Telangiectatic osteosarcoma b. Osteoblastoma c. Giant cell tumour d. Chondrosarcoma e. Osteochondroma f. Periosteal osteosarcoma g. Adamantinoma of the bone h. Aneurismal cyst i. Simple cyst j. Fibrous dysplasia k. Parosteal osteosarcoma l. Conventional osteosarcoma m. Mesenchymal chondrosarcoma n. Ewing’s sarcoma o. Chordoma p. Osteoid osteoma

EMQ B Question 2 A child presents with cranial nerve deficits and a lobulated soft tumour is excised from the cervical vertebrae. The tumour is S100 and EMA positive.

Options a. Telangiectatic osteosarcoma b. Osteoblastoma c. Giant cell tumour d. Chondrosarcoma e. Osteochondroma f. Periosteal osteosarcoma g. Adamantinoma of the bone h. Aneurismal cyst i. Simple cyst j. Fibrous dysplasia k. Parosteal osteosarcoma l. Conventional osteosarcoma m. Mesenchymal chondrosarcoma n. Ewing’s sarcoma o. Chordoma p. Osteoid osteoma

EMQ B Question 3 A 19- year-old female has a superficial diaphyseal tumour with sunburst mineral arrays and it does not involve the medulla. In microscopy malignant chondroid matrix mixes with osteoid.

Options a. Telangiectatic osteosarcoma b. Osteoblastoma c. Giant cell tumour d. Chondrosarcoma e. Osteochondroma f. Periosteal osteosarcoma g. Adamantinoma of the bone h. Aneurismal cyst i. Simple cyst j. Fibrous dysplasia k. Parosteal osteosarcoma l. Conventional osteosarcoma m. Mesenchymal chondrosarcoma n. Ewing’s sarcoma o. Chordoma p. Osteoid osteoma

EMQ B Question 3 A 19- year-old female has a superficial diaphyseal tumour with sunburst mineral arrays and it does not involve the medulla. In microscopy malignant chondroid matrix mixes with osteoid.

Options a. Telangiectatic osteosarcoma b. Osteoblastoma c. Giant cell tumour d. Chondrosarcoma e. Osteochondroma f. Periosteal osteosarcoma g. Adamantinoma of the bone h. Aneurismal cyst i. Simple cyst j. Fibrous dysplasia k. Parosteal osteosarcoma l. Conventional osteosarcoma m. Mesenchymal chondrosarcoma n. Ewing’s sarcoma o. Chordoma p. Osteoid osteoma •

EMQ B Question 4 A 35-year-old female presents with inability to flex the knee. A metaphyseal tumour is seen on the posterior aspect of distal femur, which encircles the bone.

Options a. Telangiectatic osteosarcoma b. Osteoblastoma c. Giant cell tumour d. Chondrosarcoma e. Osteochondroma f. Periosteal osteosarcoma g. Adamantinoma of the bone h. Aneurismal cyst i. Simple cyst j. Fibrous dysplasia k. Parosteal osteosarcoma l. Conventional osteosarcoma m. Mesenchymal chondrosarcoma n. Ewing’s sarcoma o. Chordoma p. Osteoid osteoma •

EMQ B Question 4 A 35-year-old female presents with inability to flex the knee. A metaphyseal tumour is seen on the posterior aspect of distal femur, which encircles the bone.

Options A. Telangiectatic osteosarcoma B. Osteoblastoma C. Giant cell tumour D. Chondrosarcoma E. Osteochondroma F. Periosteal osteosarcoma G. Adamantinoma of the bone H. Aneurismal cyst I. Simple cyst J. Fibrous dysplasia K. Parosteal osteosarcoma L. Conventional osteosarcoma M. Mesenchymal chondrosarcoma N. Ewing’s sarcoma O. Chordoma P. Osteoid osteoma

EMQ B Question 5 A lytic cystic red brown epiphyseal tumour is excised from the distal femur of a 25-year-old woman. You are told that in order to differentiate this tumour from the mimics, you have to check the calcium levels on this patient.

Options A. Telangiectatic osteosarcoma B. Osteoblastoma C. Giant cell tumour D. Chondrosarcoma E. Osteochondroma F. Periosteal osteosarcoma G. Adamantinoma of the bone H. Aneurismal cyst I. Simple cyst J. Fibrous dysplasia K. Parosteal osteosarcoma L. Conventional osteosarcoma M. Mesenchymal chondrosarcoma N. Ewing’s sarcoma O. Chordoma P. Osteoid osteoma

EMQ B Question 5 A lytic cystic red brown epiphyseal tumour is excised from the distal femur of a 25-year-old woman. You are told that in order to differentiate this tumour from the mimics, you have to check the calcium levels on this patient.

Diseases of Synovial Joints Trauma Haemarthrosis Inflammatory Infection Crystal induced Primary inflammatory Rheumatoid disease Non-inflammatory Osteoarthritis NO TUMOURS

MCQ 4 • A 44 year old man complains of swollen, tender and warm, knee joint. A biopsy of synovium shows villous hypertrophy, chronically inflamed tissue with lymphoid follicles and plasma cells. He most likely diagnosis is: a. b. c. d. e.

Septic arthritis Osteoarthritis Rheumatoid arthritis Psoriatic arthritis None of the above

MCQ 4 • A 44 year old man complains of swollen, tender and warm, knee joint. A biopsy of synovium shows villous hypertrophy, chronically inflamed tissue with lymphoid follicles and plasma cells. He most likely diagnosis is: a. b. c. d. e.

Septic arthritis Osteoarthritis Rheumatoid arthritis Psoriatic arthritis None of the above

Rheumatoid disease

Inflamed synovium (pannus) grows over and destroys articular cartilage

Villous synovium

Subluxation

Autoimmune inflammation

Osteoarthritis Focal

Cartilage loss Osteophyte Subarticular bone sclerosis

Cyst formation

Starts at surface

Process extends to deep layers By cleft formation

Eburnation

Septic arthritis

Crystal arthritis

Gout Pseudogout

•Any Questions?