This document discusses the histopathological features of various peripheral nerve tumors and vascular lesions. It provides microscopic details of traumatic neuromas, Morton neuroma, schwannomas, neurofibromas, perineuriomas, and malignant peripheral nerve sheath tumors. For vascular lesions, it describes capillary hemangiomas, cavernous hemangiomas, epithelioid hemangiomas, and glomus tumors. Immunohistochemistry markers are also mentioned. The document contains in-depth microscopic and immunohistochemical details useful for the diagnosis of various peripheral nerve and vascular tumors.
5. TRAUMATIC NEUROMAS.
Peripheral nerve severed or crushed
distal end - wallerian degeneration=proximal end-
regenerates.
Failure to meet-tangled mass of nerve fibers
Microscopy-All the elements of a nerve recognized: axons,
Schwann cells, perineurial cells, and fibroblasts
6. Morton neuroma (Morton metatarsalgia)
Repeated mild trauma -b/w 3rd and 4th toes. F>M
Microscopy-affected nerve markedly distorted.
Extensive perineurial fibrosis, -In a concentric
fashion.
Arterioles thickened and sometimes occluded by
thrombi
Palisaded encapsulated neuroma
proliferation of Schwann cells & numerous axons
within a capsule derived from perineurium
IHC- Schwann cells -S-100 protein, axons –
neurofilaments
capsule for EMA, the latter indicates perineurial
cells
7. Few truly encapsulated neoplasms
Any age; typically in adulthood
Common sites -intracranial sites (cerebellopontine
angle), posterior mediastinum, retroperitoneum, flexor
surface of extremities, and head & neck
Slow-growing, usually painless tumors
Often sporadic; <5% occur in patients with NF-2
8. Ovoid or fusiform mass, usually <5 cm
Well-defined
Typically encapsulated
Pink to tan, firm C/S
Focal areas of cystic degeneration
9. Hypercellular Antoni A areas
Hypocellular, myxoid Antoni B
Hyalinized vessels
Focal areas of hemorrhage,
hemosiderin deposition, and
xanthomatous change
Rarely -glandular structures or pure
epithelioid morphology-
benign epithelioid
10. Ancient schwannoma
◦ cytologic atypia/hyalinization
Cellular schwannoma
◦ Antoni A areas
◦ nuclear atypia, mitotic activity & focal
necrosis
psammomatous melanotic schwannoma
◦ from the spinal nerve roots
◦ low grade malignancy = local recurrence
16. Well-defined fusiform lesion -in a/w nerve trunk
Dermal or S/C tissues throughout the body
Any age -most commonly in young adults
Lesions-localized, diffuse, or plexiform, the
latter two having a strong association with NF1
NF1, von Recklinghausen disease
◦ Autosomal dominant
◦ chromosome 17
◦ Positive family history
◦ Multiple neurofibromas
◦ Café-au-lait spots
(hyperpigmented skin lesions)
◦ Lisch nodules
(pigmented iris hamartomas)
17. Not encapsulated, softer than schwannoma
Firm, gray-white cut surface
Diffuse lesions -ill-defined, plaque like
thickening of S/C tissues
Plexiform lesions-Multinodular conglomerate of
lesions -“bag of worms”
18. Combined proliferation of all the
elements of a peripheral nerve: axons,
Schwann cells, fibroblasts, and (in the
plexiform type) perineurial cells
Stroma -mucoid material- occasionally
hyalinized- Wisps of collagen
Mild nuclear atypia- common
stroma -numerous mast cells
Distorted organoid structures
resembling Wagner–Meissner or Pacini
corpuscles sometimes
May contain melanin pigment -
pigmented neurofibroma
Epithelioid morphology- Epithelioid
neurofibroma
20. Plexiform neurofibroma
◦ Almost exclusively a/w NF1
◦ Irregularly expanded nerve bundles giving a multinodular
appearance
◦ hypocellular with a prominent myxoid matrix
◦ Variable degree nuclear pleomorphism
◦ Infrequent mitotic activity
22. Schwannoma
Myxoma
Malignant peripheral nerve sheath tumor
Special Stains and IHC
● S-100 protein positive
23. Exclusively of perineurial cells
Microscopy
Extremely elongated cells arranged in parallel bundles
Some hv storiform pattern-storiform perineurial
Fibroma
Diagnosis- Myxoid lesions of soft ts in which a
storiform or fascicular pattern of growth evident
24. Variants - sclerosing perineurioma
-reticular (retiform) perineurioma
-plexiform perineurioma
-rare granular cell perineurioma
Hybrid forms of schwannoma & perineurioma
malignant forms–Representing subtype of MPNST
IHC- positive for EMA, Glut-1
& CD34
negative for S-100 protein
25. SITE- skin, soft tissues, intraspinal location
Gross & microscopy-reminiscent of myxoma, except
for prominent multinodularity with a fibrous border
& presence of plumper, epithelial-like cells &
distinct fascicular or plexiform arrangement-
plexiform myxoma
D/D
◦ Perineurioma show prominent myxoid features and a
fascicular or storiform pattern of growth
◦ Myxoid neurofibroma
*IHC some of the cells stain for
S-100 protein,
very few for EMA,
and still others for CD34.
26. An enlarging mass arising in a/w a major
nerve trunk
Proximal extremities
3% -10% of patients with NF1 develop MPNST
50% are found in patients with NF1;
often develops after 10 to 20 years
Sporadic cases typically in adults M=F
Cases A/W NF at a younger age and show
4:1 male-to-female
Origin- ? Schwann cells
27. fusiform, deep-seated mass
often within a major nerve
Typically poorly defined
Frequently infiltrate along
adjacent nerve or into
adjacent soft tissue
Tan-white, fleshy C/S
focal areas of hemorrhage &
necrosis
28. Cellular spindle cell tumor
Fascicular growth pattern
Alternating Hyper/Hypocellular
Areas of myxoid stroma
Nuclear palisading
whorled nodules of spindle cells
Perivascular tumor cell condensation
and growth along nerve twigs
hyperchromatic wavy or buckled
nuclei-Punched out nuclei
Minimal to marked pleomorphism
High mitotic activity
29. Geographic
necrosis
Benign or
malignant
heterologous
elements such as
bone, cartilage,
and skeletal
muscle may be
seen
Glands or
squamous islands
Epithelioid
malignant MPNST
35. High likelihood of local recurrence & distant
metastasis
Metastases -lungs, liver,
Bone; lymph node involvement is rare
Propensity to spread for considerable
distances along the nerve sheath
the plexiform variant of MPNST occurring in a
superficial location in children-A/W a better
prognosis
37. flat polygonal cells
connected to each other by junctional complexes
numerous pinocytotic vesicles
membrane-bound organelles-Weibel-Palade
bodies -store Von Willebrand factor.
Many metabolic functions
Concerned with the fine control of blood
coagulation, thrombosis & local control of b/v
constriction/dilatation & vessel wall permeability
38. Capillary hemangioma
(infantile & juvenile hemangioma)
Cavernous hemangioma
Most common vascular
tumor of infancy,
first few weeks of life
Site- head and neck; may
involve the S/C tissue or
occasionally the viscera
diffuse soft tissue growth
-hemangiomatosis
Typically -crimson skin
lesion -becomes raised
over time (strawberry
hemangioma)
grows thru 1st year of life
and regresses over time
Commonly in children
Site- skin of the head and
neck (port-wine nevus)
Typically involves deeper
tissue than capillary
hemangiomas do
May occur in abdominal
viscera-liver and spleen
Less likely to regress over
time
Occasionally a/w Maffucci
syndrome (multiple
enchondromas and vascular
proliferations)
a spongy, dark-red cut
surface
40. Capillary hemangioma
Lobular architecture -
arborizing, small vascular
channels
lined by plump to flattened
endothelial cells,
separated by scant connective
tissue stroma
Cellular lesions show
inconspicuous capillary lumina;
solid growth pattern and
variable mitotic activity-
(cellular hemangioma)
Involutional changes- vascular
ectasia and replacement by fat
or fibrous tissue
Mast cells may be numerous
41. Cavernous hemangioma
Typically in subcutaneous tissue
Dilated, blood-filled, medium- to large-caliber vascular spaces,
lined by flat endothelial cells
Large, deep cavernous hemangiomas may undergo thrombosis,
ulceration, and infection .
Thrombi seen in various stages of organization and
recanalization, the latter including papillary endothelial
hyperplasia (Masson lesion).
42. Epithelioid hemangioma
Angiolymphoid hyperplasia with eosinophilia
head and neck - pruritic red lesion
may be multifocal -May recur
Well-circumscribed dermal lesion - small-medium-sized b/v
Vascular channels lined by plump endothelial cells with abundant
eosinophilic cytoplasm and vesicular oval nuclei
B/g typically- a lymphocytic infiltrate, with germinal centers;
variable numbers -mast cells, eosinophils, & plasma cells
Pyogenic granuloma (lobular capillary hemangioma ) [LCH])
Typically a polypoid growth in the skin or oral mucosa
Commonly a/w pregnancy or 0CP use
Well circumscribed - lobular architecture
small, arborizing vascular channels & bland endothelium
Intramuscular angioma
Capillary or cavernous channels admixed with mature skeletal
muscle and a variable amount of fat- MAY RECUR
43. Spindle cell hemangioma
Subcutaneous nodule on distal extremity
Poorly circumscribed lesion, any age ,m>f
Biphasic population of solid masses of spindle cells
combined with cavernous vascular channels;
may contain thrombi
described as a low-grade angiosarcoma
A non-neoplastic lesion related to a vascular malformation
45. Thrombomodulin, CD34, CD31, and Fli-1
highlight endothelial cells
GLUT1 positive in capillary hemangioma of
juvenile type only
47. First described by Masson in hemorrhoidal
vessels as ‘vegetant intravascular
hemangioendothelioma’
Exuberant organization & recanalization of a
thrombus
can occur in previously normal vessels or in
varices, hemorrhoids, hematomas, pyogenic
granulomas, hemangiomas, and
angiosarcomas
49. Tumor differentiates toward modified smooth muscle of
the glomus body-Neuromyoarterial glomus- a normal
arteriovenous shunt abundantly supplied with nerve
fibers and fulfilling a temperature-regulating function
Age- young adults
Site- distal extremities,esp fingers and toes
deep or visceral tumors -rare
Red and blue subcutaneous nodule -painful
may be multifocal
Subungual lesions supplied by numerous nerve fibers
=exquisitely painful,
Gross
Typically smaller than 1 cm;
well-circumscribed dermal or subcutaneous nodule
50. Sheets or nests of uniform, round epithelioid cells
with oval nuclei and pale eosinophilic cytoplasm
Groups of glomus cells may surround dilated
vessels (glomangioma)
Minimal mitotic activity
May show focal degenerative nuclear atypia
51. solid type-confused with sweat gland tumor, melanocytic
nevus, or metastatic carcinoma.
-particularly when tumor cells very epithelioid and/or grow
in an Indian-file fashion.
angiomatous type -diffuse quality, looking like an
angiomatosis with an increased number of glomus cells in the
vessel wall
oncocytic variant -cytoplasm of the glomus cells is packed with
mitochondria,. Mast cells are common
52. SMA and h-caldesmon positive
CD34 variably +
CD31 and thrombomodulin -ve in tumor cells
Prognosis
Benign and typically treated by excision; 5% to 10% recur
Malignant (glomangiosarcoma)- exceedingly rare
-defined as glomus tumors with a deep location and a size
of more than 2 cm, or atypical mitotic figures, or moderate
to high nuclear grade and five or more mitoses per 50
high-power fields.
54. Hemangiopericytoma
Borderline malignant potential
Shows differentiation toward modified pericytes
Adults;
Usually deep, mostly in legs, pelvis, retroperitoneum
Often large on clinical detection
GROSS
Solitary, well-circumscribed, often lobulated
Gray-white to red-brown cut surface
Focal hemorrhage or cystic degeneration seen
55. Hemangiopericytoma
Thin-walled staghorn vascular channels
lined by a single layer of flat endothelium,
surrounded by perivascular and intervascular proliferation of
uniform-appearing oval to spindle-shaped pericytes
ill-defined cytoplasmic borders
Reticulin-rich network surrounding individual pericytes
Focal hyalinization & myxoid change
Mitotic rate typically <4 mitotic figures/10 hpf
variable admixed adipose tissue “lipomatous hemangiopericytoma”
57. Criteria not clear
Aggressive behavior
Brisk mitotic activity, nuclear atypia, necrosis,
and hemorrhage;
All hemangiopericytomas have at least borderline
malignant potential
58. Same as hemangiopericytoma, except with
plump, spindled to round myoid cells that
surround vessels with a hemangiopericytoid
pattern
Subcutaneous lesion
Distal extremities
Special Stains and Immunohistochemistry
CD34: equivocal positivity
SMA positive in myopericytoma but negative in
conventional hemangiopericytoma
Myopericytomas that occur in the setting of
immunodeficiency are associated with EBV.
59. Solitary fibrous tumor
Fibrous histiocytoma with hemangiopericytoma-
like areas
Glomangioma
Synovial sarcoma (monophasic)
A diagnosis of exclusion because the
hemangiopericytoma-like pattern may be seen in a
variety of other tumors
Metastases may appear 10 to 20 years later and
usually involve lung or bone
60. Hemangiopericytoma-like pattern of growth
Synovial sarcoma
MPNST
Mesenchymal chondrosarcoma
◦ (Contains areas of relatively mature cartilage)
Phosphaturic mesenchymal tumor
◦ hemangiopericytoma-like areas a/w osteoclast-like
cells, cartilage, and other patterns
infantile fibrosarcoma
thymoma
◦ Exhibit epithelial markers
61. Epithelioid
hemangioendothelioma
Retiform hemangioendothelioma
and papillary intralymphatic
angioendothelioma
(Dabska tumor)
Any age-rare in children
Site-dermal or S/C tissues
of extremities
Rarely multicentric
Bone/visceral involvement
possible
Often surrounds a
preexisting blood vessel,
most commonly a vein
May be a/w edema or
thrombophlebitis
Metastasis in 33%
All ages; more
common in adults
Dabska tumor more
common in children
Limbs -most
commonly affected
ability to recur but rare
metastasis
62. Violaceous plaques or subcutaneous nodules
Often multinodular
Infiltrative borders
Gray to white variegated cut surfaces
Epithelioid hemangioendotheliomas a/w
large vessels may resemble organizing
thrombi
63. Epithelioid hemangioendothelioma
Cords and nests of polygonal endothelial cells
Intracellular cytoplasmic lumens with intraluminal RBC’s
Intramural growth into preexisting vessels
perivascular extension of tumor
Bland, round to oval nuclei + eosinophilic cytoplasm
Background stroma- myxoid or hyalinized
Low mitotic rate
64. Retiform hemangioendothelioma &
papillary intralymphatic angioendothelioma
(Dabska tumor)
Both tumors- Plump cells lining lymphatic-like vascular
channels, with or without intraluminal papillary projections
Retiform hemangioendothelioma- narrow, arborizing vascular
spaces separated by sclerotic stroma, a lymphocytic infiltrate
Dabska tumor = Intraluminal tufts of plump endothelium
Resembles deep lymphangioma;
Deposits of basement membrane
seen in cellular tufts
67. Rare tumor ; <1% of sarcomas
Usually seen in adults
Predilection for skin and superficial soft tissue,
breast, bone, liver, spleen
Rare in deep soft tissue
May be a/w chronic lymphedema (typically
postmastectomy), previous therapeutic radiation,
or AV fistulas in renal transplant recipients
Angiosarcomas of liver are a/w prior exposure to
polyvinyl chloride and thorium dioxide
(Thorotrast)
68. Cutaneous angiosarcoma- as an ill-defined,
bruiselike lesion or ulcerated hemorrhagic
nodules, or plaques simulating erysipelas
Commonly large hemorrhagic, ill-defined masses
with spongy quality and blood-filled spaces and
deeply invasive
69. •Primarily constituted by epithelioid or fusiform cells
Rudimentary vascular differentiation;
pleomorphism, mitoses, and widespread tissue
infiltration
•Tumor cells in vascular spaces may be attenuated or
plump with hyperchromatic nuclei
•Spindle cell areas may resemble fibrosarcoma or other
spindle cell tumors
72. •Thrombomodulin, CD31, CD34, and Fli-1
positive
•Cytokeratin may be +ve in epithelioid variant
Other Techniques for Diagnosis
•Electron microscopy may demonstrate
cytoplasmic Weibel-Palade bodies in roughly
25% of cases
73. Hemangioma
Papillary endothelial hyperplasia
(intravascular hemangioendothelioma of
Masson)
Epithelioid hemangioendothelioma
Metastatic renal cell carcinoma, because of its
high degree of vascularity
(no clear cells in angioSA)
74. Treatment
◦ radical surgery and radiation therapy
recurrence and distant metastasis
◦ most commonly to lungs, lymph nodes, and bone
Prognosis
◦ Related to size, multifocality, and ability to achieve
a complete excision
75. Slowly progressive multifocal vasoproliferative
lesion
low-grade malignancy-in the AIDS population
In persons with other forms of
immunosuppression
◦ organ transplant recipients
◦ An A/W the systemic form of Castleman disease
◦ Angioimmunoblastic lymphadenopathy (two disorders of
the immune system)
◦ AIDS, Kaposi sarcoma- predominantly a feature of
homosexual population
◦ Also seen in heterosexual drug users
76. Multiple blue dermal plaques or nodules
Starting on the feet and legs
Ocasionally a pedunculated appearance
reminiscent of pyogenic granuloma
Temporary control by irradiation, chemotherapy,
or, if the lesion is sharply delimited, excision.
Course – variable
◦ Increased incidence of malignancy- lymphoid type
◦ Lymph nodes and the GIT most commonly involved.
◦ Indicators of poor outcome-immunosuppression &
age>50 yrs
77. Classic Kaposi sarcoma
Affects -males of Eastern European /Mediterranean
Slowly developing nodules/plaques affecting lower
extremities
Endemic Kaposi sarcoma
Native blacks in Central Africa
Younger patients and children
Epidemic Kaposi sarcoma
In immunocompromised states
A/W HIV infection
Typically involves trunk and mucosal surfaces
Kaposi sarcoma a/w iatrogenic immunosuppression
Immunosuppressed states, a/w Rx for transplant
rejection,
78. Typical feature-spindle cells
forming slits containing RBC’s
Mitotic activity –moderate
Peomorphism -usually absent.
Admixed-Lymphocytes,
hemosiderin-laden
macrophages, & other
inflammatory cells.
Variously sized PAS +ve
hyaline bodies, seen in the
cytoplasm of the proliferating
cells and sometimes
extracellularly =Represent the
result of ingestion and
degradation of erythrocytes
and – -not specific
79. Early lesions-Spindle proliferation limited to
the papillary dermis and to the vascular
plexus surrounding the secretory coil of
sweat glands
80. Early patch stage
Slitlike spaces b/w collagen bundles that often follow adnexal
structures & preexisting blood vessels that appear to protrude into
newly formed blood vessels (promontory sign)
Extravasated RBC’s & plasma cells may be present
Plaque stage
spindle-shaped cells proliferation,arranged as short fascicles
Diffuse proliferation of blood vessels
Intracytoplasmic hyaline globules
Nodular stage
Well-defined nodules of vascular spaces
Spindle-shaped cells replace the dermis
Hemosiderin-laden macrophages in the vicinity
Intracellular & extracellular hyaline globules
Late aggressive lesions of Kaposi sarcoma
Features of an aggressive sarcoma
Greater degree of cytologic atypia and high mitotic rate
81. Special Stains and Immunohistochemistry
Hyaline globules-PAS +ve & diastase resistant
Vascular nature-confirmed by immunostains
CD31 and CD34
Other Techniques for Diagnosis
Demonstration of
◦ HHV-8
82. Early lesions -from benign vascular
proliferations
◦ Targetoid hemosiderotic hemangioma
◦ Fibrous histiocytoma
◦ Kaposiform haemangioendothelioma
Late aggressive forms-from other aggressive
sarcomas and require IHC
◦ Angiosarcoma