Morning report

Supervisor: Dr. Nader Haddad

Resident: Basheer Alakhras
13-10-2024
Clinical data
• a 30 year old male PT admitted to general surgery ward as a case of
abdominal wall mass (for elective surgery). Pt have old hx of small
mass years ago that started to increase in size a year earlier.
• Exam: Stable vital signs, no thrill and no visible pulsation pt have
suprapubic fixed hard mass extending from infraumbilical region to
symphysis pubis, without skin alteration.
MRI
• There is a large anterior lower abdominal wall soft tissue mass
measuring about 100 × 130 x 130 mm, the lesion is heterogenous
mildly hyperintense at both Il and 12 images. The lesion is associated
with marked diffusion restriction and shows heterogenous
enhancement postcontrast. It is seen extending into the cavity of the
lower abdomen. The urinary bladder and other intra-abdominal
organs are intact. There are multiple peri and intra-lesion signal voids.
There is a large malignant appearing left-sided external iliac lymph
node measures about 33 x 42 mm. Overall picture is suspicious for
malignancy and correlation with tissue biopsy is advised
Grossly
• - Received three containers:
• No.1 The specimen is fixed in formalin and received in a properly labeled container with the
patient's name and identity number, designated as "Appendix", and consists of an appendix
measuring 4x1x1cm. Grossly looks unremarkable. Resection margin is inked purple.
• No.2 The specimen is fixed in formalin and received in a properly labeled container with the
patient's name and identity number, designated as "abdominal wall mass/soft tissue mass"
and consists of a single lesion measuring 15x14x11cm. Step sectioning revealed
heterogenous hemorrhagic, solid cut surface with areas of necrosis. 2 lymph nodes were
harvested.
• No.3 The specimen is fixed in formalin and received in a properly labeled container with the
patient's name and identity number, designated as "lymph node", and consists of a single
fragment of grey tissue measuring 4x4x3cm. Step sectioning revealed heterogenous
hemorrhagic cut surface.
DDX
• Alveolar soft part sarcoma
• Metastatic renal cell carcinoma
• Metastatic adrenal cortical carcinoma
• Metastatic hepatocellular carcinoma
• Malignant peripheral nerve sheath tumor, epithelioid variant
• Melanoma
• Alveolar rhabdomyosarcoma
Metastatic RCC
• ninth most common cancer in men and fourteenth most common in
women
• M:F = approximately 2:1
• Risk factors: obesity, smoking, hypertension, acquired cystic kidney
disease due to end stage renal disease, occupational exposure to
trichloroethylene, treated neuroblastoma
• Genetic susceptibilities estimated to account for 2 - 4%
• Usually > 50 years old
Most common metastatic sites
• Lung, bone, lymph nodes and liver.
Microscopy
• Tumor cells have abundant cytoplasm that is vacuolated, fluffy or
granular, usually with indistinct cell borders (chromophobe renal cell
carcinoma has distinct borders)
• Tumor nuclei have variable atypia, irregular contours, haphazard
orientation with abnormal chromatin, variably prominent nucleoli
• Important features: heterogeneous cell population, small cytoplasmic
vacuoles and hemosiderin deposits
Positive stains
• RCC
• PAX8
• CAIX (75-100%) in clear cell rcc
• CD10
• Vimentin
• PanCK
• CAM5.2
• EMA
Metastatic Adrenal cortical
carcinoma
• Median age 55 - 56 but can occur at any age
• More common in females and whites; M:F = 1:1.5 - 2.5
• 90% are sporadic
• Genetic susceptibility in 5 - 10%
multiple endocrine neoplasia type 1 (MEN1), Lynch, Li-Fraumeni,
Beckwith-Wiedemann, adenomatous polyposis coli (APC) and
neurofibromatosis type 1 (NF1) syndromes, Carney complex and
congenital adrenal hyperplasia
• ~50% are functional and ~50% are nonfunctional
Most common metastatic sites
• local periadrenal tissue, lymph nodes, lungs, liver, and bone
Microscopy
• Encapsulated tumor composed of variably sized nests, large sheets
and trabeculae
• Invasion of thick fibrous capsule
• Lymphovascular invasion (venous or sinusoidal)
• Areas of necrosis, hemorrhage, degeneration are common
• Large cells with granular clear to eosinophilic cytoplasm, often
pleomorphic
• Frequent intranuclear inclusions, mitoses, atypical mitoses
Positive stains

• Steroidogenic factor 1 (SF1)

• Calretinin
• inhibin,
• MelanA / MART1
• synaptophysin
• neuron specific enolase (NSE)
• IGF2
• Vimentin
• p53
• INSM1,
• CAM 5.2
Metastatic hepatocellular carcinoma
• Most common (> 80%) primary liver malignancy worldwide
• ~ 80% of hepatocellular carcinoma cases arise in cirrhosis
• Incidence and age of onset vary geographically: Asia (72.5%) has the
highest incidence worldwide
• Median age of onset in Asia and Africa is between third and sixth
decades
• M:F = 3:1
• Risk factors:Chronic liver disease leading to cirrhosis; most common
etiologies leading to this include chronic viral hepatitides (HBV and
HCV), heavy alcohol consumption, nonalcoholic fatty liver disease
Most common metastatic sites
• Lung, portal vein, portal lymph node, intra-abdominal lymph node,
bone
Microscopy
• Architectural patterns:4 principal growth patterns, including
trabecular, pseudoglandular, solid and macrotrabecular
• Cytologic features: Polygonal cells with nuclear atypia, including high
N/C ratio, irregular nuclear membrane, multinucleation and
prominent nuclei. Cytoplasm varies from clear to eosinophilic,
depending on the fat and glycogen content. Cytoplasmic alterations
include Mallory-Denk bodies, hyaline bodies, pale bodies. Bile
production (usually extracellular) may be seen
Positive stains
• Arginase1: cytoplasmic or nuclear; highly sensitive and specific
• HepPar1: cytoplasmic and granular; overall highly sensitive but 50%
of poorly differentiated hepatocellular carcinoma lose expression
• Glypican 3: cytoplasmic; high sensitivity in poorly differentiated and
scirrhous hepatocellular carcinoma but low sensitivity in well
differentiated hepatocellular carcinoma (nonneoplastic liver is
negative)
• AFP: cytoplasmic; highly specific but low sensitivity; frequently
negative in well differentiated hepatocellular carcinoma
• Reticulin: highlights the thickened hepatocyte plates (> 3 cell thick
Malignant peripheral nerve sheath
tumor
• Sarcoma with peripheral nerve sheath differentiation with typically
aggressive behavior
• Can occur in the following settings:
• Sporadic (~ 50%)
• In neurofibromatosis type 1 (40 - 50%)
• In the setting of prior radiation therapy (10%)
• Plexiform neurofibromas are seen in approximately 50% of patients
• 10 - 15% of plexiform neurofibromas transform to MPNST
• No gender predilection
• Marbled appearance due to alternating hypocellular and hypercellular
areas with perivascular accentuation
• Epithelioid MPNST Rare subtype, usually not associated with NF1
• Rare cases may arise in epithelioid Schwannoma
• Distinct molecular features from conventional MPNSTs and
harbor SMARCB1 gene inactivation and INI1 loss in up to 40 - 67% of
cases
Positive stains
• Typically have diffuse and strong expression of S100 and SOX10 in
epithelioid variant
• Desmin, myogenin and MyoD1 in rhabdomyosarcomatous elements
Melanoma
• Incidence: 3 - 7% (Europe), 2.6% (U.S.)
• 1% of skin cancer
• Higher incidence in periequatorial zone
• M:F = 1.5:1
• Risk factors
• Fair skinned populations
• Family and personal history of melanoma
• Intense intermittent sun exposure (or artificial UV radiation sources)
• Increased mole count (> 50)
• Dysplastic nevus phenotype
• Germline mutation in CDKN2A, CDK4, MITF, TERT, ACD, TERF2IP, POT1, MC1R or BAP1 genes
• Immunosuppression
Sites
• Cutaneous melanoma: anywhere on the skin's surface, including
subungual location
• Frequent sites
• Lower extremities (female)
• Trunk (male)
• Extracutaneous
• Uvea
• Anorectal region
• Upper aerodigestive tract
• Sinonasal tract
• Leptomeninges
Microscopy
• Cytologic features
• Epithelioid / spindle shaped cell
• Nuclear pleomorphism
• Nuclear enlargement
• Nuclear hyperchromasia
• Coarse irregular chromatin pattern with peripheral condensation ("peppered moth"
nuclei) Prominent eosinophilic nucleoli
• Dusty pigmented cytoplasm
Positive stains
• S100 (nuclear and cytoplasmic)
• SOX10 (nuclear)
• MelanA / MART1 (cytoplasmic)
• HMB45 (cytoplasmic)
• Tyrosinase (cytoplasmic)
• MiTF (nuclear)
• Masson Fontana histochemical stain to highlight cytoplasmic melanin
pigment
Alveolar rhabdomyosarcoma
• High grade, cellular, round cell sarcoma with evidence of skeletal
muscle differentiation
• Predilection for deep soft tissue of lower extremities
• High stage at presentation with overall worse prognosis
• Other sites include head and neck, trunk, paraspinal, pelvic,
genitourinary regions and retroperitoneum
• Can present with widespread involvement, such as bone marrow
infiltration (leukemia-like presentation) and lymphadenopathy
• 25 - 30% of patients present with metastatic disease
Most common metastatic sites
• lung and lymph nodes
• Can metastasize to other sites such as the bone; however, rare
visceral metastases to brain, breast, kidney and pancreas have also
been reported
Microscopy
• Cellular round cell tumor
• Large clusters, nests, cords and trabeculae of primitive round cells, separated by variably thick
fibrovascular septa
• Loss of cellular cohesion in the center forms alveolar-like, cystic and vague papillary appearance
• Layer of cells adheres to the periphery of the spaces and fibrous septa
• Small to intermediate sized monomorphic cells with scant cytoplasm
• Hyperchromatic nuclei with variable conspicuous small nucleoli
• Cells in the center have poor preservation and are necrotic; may appear floating
• Multinucleated tumor giant cells with wreath-like lineup of nuclei are common
• Round to oval rhabdomyoblasts with abundant acidophilic cytoplasm may be present
• Brisk mitosis and variable tumor necrosis
• Occasional cases may show clear cell morphology with pale, glycogenated cytoplasm
Positive stains
• Stains for myogenic differentiation:
• Desmin
• Myogenin (strong and diffuse)
• MyoD1 (variable)
• Muscle specific actin (variable)
• PAX3::FOXO1 / PAX7::FOXO1 fusion specific antibodies
Alveolar soft part sarcoma
• Rare sarcoma of uncertain histogenesis
• specific translocation, der(17)t(X;17)(p11.2;q25), resulting
in ASPSCR1-TFE3 gene fusion
• Predominantly affects the deep soft tissues of the extremities (thigh
and buttock) in young adults and head and neck region (tongue and
orbit) in children
• Accounts for < 1% of all soft tissue sarcomas
• age range is 1 - 78 years (median: 25 years)
• Female predominance (less pronounced in older >30 and children)
• Commonly involves deep soft tissues of the extremities
(61%; predominantly the lower extremity [51%]), trunk (20%), internal
organs (8%) and head and neck (9%)
• In adults thigh and buttock
• In children head and neck
• No association with radiation or a cancer predisposition syndrome has
been reported
Clinically
• Slow growing, painless mass
• At presentation, the tumor can be localized (38%), regional (11%) and
metastatic (43%)
• MRI shows characteristic vascular pattern and moderate to intense
postcontrast enhancement, may mimic AV malformation on
angiography.
• Metastases often occur > 10 years after diagnosis and involve the
lungs, liver, bone, brain and (rarely) lymph nodes
• Metastatic involvement of the brain is more common in ASPS than
any other sarcoma
Grossly
• Solid, partially circumscribed mass with fleshy nodules and fibrotic
bands
• Usually yellow to gray to white-tan
• Tumor size varies from 1.2 to 24 cm (median: 6.5 cm)
• Frequently has large vessels at the periphery
Microscopic description
• Large, round to polygonal cells with well defined cell borders
• Usually little variation in individual tumor cell size
• Abundant eosinophilic granular cytoplasm
• Round, vesicular nucleus with a prominent nucleolus
• Organoid and nest-like growth pattern
• Central discohesion results in characteristic pseudoalveolar-like structures
• Lobules of tumor are divided by thick fibrous septa and rich capillary vascular network
• Dilated veins usually present at the periphery of the mass
• Vascular invasion is common
• Cytoplasmic clearing, rhabdoid cells, pseudoglandular pattern and cystic / myxoid change may be seen
• Uncommon features: nuclear pleomorphism, hyperchromasia, giant cells, mitotic figures, necrosis,
calcification, lymphocytic infiltrate and xanthomatous features
• Tumor frequently show intracytoplasmic rod-like or rhomboid crystalline structures, focally or diffusely
Positive stains
• TFE3
• Cathepsin K is typically positive
• PAS highlights intracytoplasmic crystals and granules (PAS positive /
diastase resistant)
TFE3
SMA
Negative stains
• PAX8 • EMA • Caldesmon
• RCC • Synaptophysin • Desmin may be
• CAM5.2 • Chromogranin focally positive
• HebPar1 • HMB45 • Vimentin and NSE ma
y be positive in 30 -
• Inhibin • MelanA 50%
• Galactin3 • Calretinin (46%) may • Myogenin
• MSA be positive
• MyoD1
• Pancytokeratin • SMA may show
nonspecific staining
Treatment
• Radical surgical resection is the treatment of choice
• Adjuvant chemotherapy does not seem to be effective
• Radiation may reduce the risk of local recurrence
• overall prognosis is poor
• Positive prognostic factors: small tumor size (< 5 cm), absence of
metastases at presentation, younger age at diagnosis (< 10 years),
early detection at a completely resectable stage
• Negative prognostic factors: older age, tumor size > 10 cm, distant
metastasis at diagnosis, primary site in the trunk