Perivascular epithelioid cell tumors (PEComas) are mesenchymal neoplasms defined by the presence of distinctive perivascular epithelioid cells. They can arise in various organs. Angiomyolipoma and lymphangioleiomyomatosis are examples of PEComas that arise in the kidney and lung respectively. Angiomyolipoma is a typically benign tumor composed of blood vessels, smooth muscle, and fat cells, while lymphangioleiomyomatosis involves proliferation of perivascular epithelioid cells around lymphatics leading to cyst formation in the lungs. The pathological features, diagnosis, and management of these PEComa subtypes were discussed in

1. Presenter-Dr Shreya Prabhu
Moderator-Dr Jyothi A Raj
1

2.  Perivascular epithelioid cell tumors are
mesenchymal neoplasms defined by the
presence of histologically and
immunohistochemically distinctive perivascular
epithelioid cells
 Growing family of tumors
2

3. Tumor family includes:
 Angiomyolipoma (renal and extrarenal),
 Clear cell "sugar" tumor (lung and extrapulmonary)
 Lymphangioleiomyomatosis
 Tumors of falciform ligament/ ligamentum teres, skin,
uterus and other viscera and soft tissue
3

4. A number of spindled and epithelioid neoplasms that
have been referred to by a variety of names, including
 Primary extrapulmonary sugar tumor (PEST)
 Clear cell myomelanocytic tumor
 Abdominopelvic sarcoma of perivascular epithelioid
cells
4

5. ANATOMIC LOCATIONS:
 Retroperitoneum
 Lung
 Uterus,cervix
 Colon
 Pancreas
 Heart
 Adrenal gland
 Breast
 Biliary tract
 Urinary bladder
 Skull base
 Liver
 Skin
 Nasopharynx
 Upper airway
 Bone
 Soft tissues
 Eye
5

6. What is the perivascular epithelioid cell?
 It has morphologic, epithelioid appearance with a
clear to granular cytoplasm, a round to oval, centrally
located nucleus and an inconspicuous nucleolus.
 A typical perivascular location, nested architecture
 At present, PEC has not a known normal
counterpart.
6

7. 7
 PEC can have a variable histologic appearance
 Epithelioid
 Elongated and spindle shaped
 Vacuolated (adipocyte-like)
 Typically
 Epithelioid cells- in an immediate perivascular
location
 Spindled cells- often away from vessels
 Typical feature
 Focal association with blood vessel wall
 Radial arrangement of tumor cells
 Subendothelial growth

8. PATHOGENESIS:
8
 Loss of TSC genes on chromosomes 9q34 (TSC1)
and 16p13 (TSC2)
 Loss of hamartin and tuberin expression, the
products of TSC1 and TSC2 genes
 Results in loss of control of cell signaling related to the
mtor pathway, with a variety of downstream effects
(genes which have a role in the regulation of the Rheb/mTOR/p70S6K
pathway)
 Progesterone receptor positivity has been described
in PEC with spindle morphology
 Suggesting a possible role of progesterone in this
morphologic modulation
 Cytogenetics- show trisomy 7 or 8

9.  It is thought that PEC can modulate its morphology
and immunophenotype
 Show epithelioid feature with a strong positivity for
HMB45
 Show muscular features with a spindle shape and a
stronger positivity for actin
 Show cytoplasmic vacoules acquiring the feature of an
adipocyte
9

10. 10

11. CYTOLOGY
11
 Small and large cohesive clusters of bland
epithelioid to spindle cells with oval or elongated
nuclei, indistinct nucleoli, finely vacuolated
cytoplasm
 Delicate transgressing vessels
 Background naked nuclei
 Rare intranuclear pseudoinclusion

12. 12
Sheets of bland-appearing spindle cells with
oval to elongated nuclei, indistinct nucleoli,
and finely vacuolated cytoplasm
Cohesive clusters of bland-appearing
epithelioid cells with oval to elongated nuclei,
indistinct nucleoli and scant to moderate
basophilic cytoplasm

13. 13

14. IHC
PEComas express
myogenic and
melanocytic
markers:
• HMB45,
• HMSA-1,
• MelanA/Mart1,
• Microophtalmia
transcription
factor (Mitf),
• Actin
• Desmin
14

15. ULTRASTRUCTURAL ANALYSIS PEC contains
 Abundant
cytoplasmic
glycogen
 Microfilament
bundles with
electron-dense
condensation
 Numerous
mithochondria
 Membrane-
bound dense
granules
 Presence of
premelanosom
es
15

16. MALIGNANT POTENTIAL:
16
 Prevalence of aggressive biological behaviour (
including both local recurrence and metastasis) is
extremely variable, ranging from 5% to 66%
 Malignant PEComa can be a very aggressive
disease leading to multiple metastases and death as
expected with a high-grade sarcoma
 Malignant PEComas-NOS- MC originating in the
uterus and others arising in the jejunum, prostate,
pelvis, skull base, broad ligament, and somatic soft
tissue
 Metastatic sites- Liver, lymph nodes, lung and bone

17. 17

18. 18

19. ANGIOMYOLIPOMA
19

20.  Benign neoplasm composed of fat, smooth muscle
and blood vessel in varying proportion.
 Arising most commonly in one or both kidneys as a
solitary or multicentric mass
20

21. Extrarenal sites of AML include
 Liver
 Nasal cavity
 Oral cavity
 Colon
 Lung
 Skin
21

22. CLINICAL FEATURES:
 Females> males
 Age- 5th decade
 Abdominal or flank pain, hematuria, or chills and
fever asymptomatic
 Sudden, severe flank pain and shock are caused by
rupture of the tumor and massive perirenal or
retroperitoneal hemorrhage
22

23.  ~1/3rd of patients present with manifestations of
Tuberous sclerosis-
 Hyperpigmented spots
 Shagreen patches
 Periungual fibromas,
 Angiofibromas to renal cysts
 Cardiac rhabdomyoma
 Gliosis and calcification of the cerebral cortex with mental
deficiency
23

24.  PEComas of the kidney include :-
1. Classic AML
2. Microscopic AML (so-called microhamartoma)
3. Intraglomerular lesions
4. Cystic AML
5. Epithelioid AML
6. Oncocytoma-like AML
7. Lymphangiomyomatosis of the renal sinus
24

25. GROSSLY
 Yellow to gray mass,
 Size-few centimeters to 20 cm or more (average
9cm)
 Large lesions may become attached to the
diaphragm or liver
 Focal hemorrhage in about half of the cases
 Well delineated from the surrounding renal
parenchyma
25

26. 26

27. Microscopically, composed of :
 Mature adipose tissue with some variations in cellular
size and nuclear appearance
 Convoluted thick-walled blood vessels with little or no
abnormal elastica and frequent hyalinization of the
media
 Irregularly arranged sheets and interlacing bundles of
smooth muscle (spindle or ovoid) often with a
prominent perivascular arrangement
27

28. 28

29. 29

30. 31
Lipomatous component in angiomyolipoma can be dominant in areas
containing variable numbers of scattered or clustered smooth muscle–like cells

31. 32
Vascular and perivascular features in angiomyolipoma.
(A–C) Tumor cells forming perivascular whorls.
(D) Vascular myointimal proliferation in an angiomyolipoma vessel

32. 33
Smooth muscle-like spindle cell element in typical angiomyolipoma

33. 34
Epithelioid angiomyolipoma shows a sharp demarcation between the typical
spindle cell and the epithelioid element.
(B–D) The epithelioid cells have abundant cytoplasm, and some cells are
multinucleated and may resemble ganglion cells or histiocytes

34. Oncocytoma-like
angiomyolipomas
• Rare tumours
consisting of a
homogeneous
population of
polygonal cells
with strongly
eosinophilic
cytoplasm
• In patients with
and without
tuberous
sclerosis
35

35. MICROSCOPIC
AML
• Small nodules
with some
features of
angiomyolipoma
• Often composed
predominantly of
epithelioid smooth
muscle cells
• The proportions of
spindle cells and
adipocytes
increase as the
lesions grow
larger
36

36. MALIGNANT POTENTIAL:
37
 Typical renal AML virtually always acts in a clinically
benign fashion, even those with atypical features
 No evidence that the presence of regional or
systemic lymph node involvement, perirenal satellite
tumors, or angiomyolipomatous growth in other
organs reflects malignant potential

37. 38
 Presence of three or more of the following features is
predictive of malignant behavior:
(1) ≥70% atypical epithelioid cells (polygonal cells with
prominent nucleoli and nuclear size exceeding twice the
size of adjacent nuclei)
(2) ≥2 mitotic figures/10 hpf
(3) Atypical mitotic figures
(4) Necrosis
 Metastatic potential, especially those cases showing
necrosis and/or marked nuclear atypia

38. 39

39. D/D:
 Liposarcoma
 Leiomyosarcoma-The myoid cells of AML tend to be
plumper and paler than those found in
leiomyosarcoma
 Renal cell carcinoma
40

40. Angiomyolipoma
with an area
composed of
atypical spindle-
shaped smooth
muscle cells
arranged in
fascicles. These
areas could be
confused for
leiomyosarcoma
41

41. Angiomyolipoma
composed of
uniform small
epithelioid smooth
muscle cells, feature
that could be
mistaken for renal
cell carcinoma
42

42. HMB-45
immunoreactivity
in smooth
muscle
43

43. TREATMENT
44
Surgical and excision
 Partial nephrectomy
 Total nephrectomy in large tumors

44. LUNG
PEComas of the lung include :-
 Lymphangioleiomyomatosis
 Clear-cell “sugar” tumor
45

45. LYMPHANGIOMYOMA AND
LYMPHANGIOMYOMATOSIS
46

46.  Lymphangiomyomatosis (LAM) is a rare disease
characterized by a proliferation of perivascular
epithelioid cells around lymphatics and lymph nodes
of the mediastinum, retroperitoneum, and the
pulmonary interstitium.
 Lymphangiomyoma- Localized lesions, mass like
involvement of lymph node
 Lymphangiomyomatosis- Extensive lesions
involving large segments of the lymphatic chain with
or without pulmonary involvement are designated.
47

47. CLINICAL FINDING
 >Females, ~40 years
 Progressive dyspnea (constant presence of chylous
pleural effusion or to pulmonary involvement)
 Pneumothorax, hemoptysis, chylous ascites, and
chyluria
48

48. Markedly dilated lymphatic vessels
suggesting proximal obstruction
49
Massive (chylous) effusion is present
Coarse reticular nodular infiltrate with
bulla
Numerous thin-walled cysts are noted

49. PATHOLOGIC FINDING
 Red to gray spongy masses that preferentially
replace the thoracic duct and mediastinal lymph
nodes.
 Form solitary or multiple masses that usually
measure <5 cm but can be >10 cm
 In dramatic cases- the entire lymphatic chain from
neck to inguinal region is transformed into multiple
confluent masses
 Chylous effusion/ chylous cysts is encountered
 In some instances the pleural surfaces are noted to
“weep” fluid, suggesting the presence of numerous
abnormal communications between the lymphatics
and the pleural surface.50

50. 51
When the process affects the lungs as well, the organ has a honeycomb
appearance with formation of numerous blebs or bullae.

51. MICROSCOPY
 Microscopic nodules in the walls of the peripheral
airways involving the interstitial lymphatics
 Foci of lymphangiomyoma are seen perivascularly,
peribronchially, and interstitially, often associated
with emphysematous cyst formation
 The smooth muscle cells resemble those of
angiomyolipoma and have a “hollow” vacuolated,
clear cell appearance
52

52. 53
Lymphangiomatosis involving large
lymphatic channels
Lymphangiomyo
ma

53. A)
Lymphangiomyoma
with distinctive
partially vacuolated
smooth mucle
surrounding
endothelium lined
spaces
B) Showing focal
positivity with HMB-
45
55

54.  The primary lesion-
 Haphazard proliferation of smooth muscle cells that
surround arterioles, venules, and lymphatics and which
diffusely thicken the alveolar septa
 Secondary changes-
 Bulla formation, as a result of air trapping by obstructed
bronchioles, and hemorrhage and hemosiderin
deposition as a result of venule destruction
56

55. D/D-
Metastatic
leiomyosarcoma
60

56. CLEAR CELL SUGAR TUMOR
61

57.  It was originally described in the lung
 Presents as a solitary pulmonary lesion
 Usually incidental radiologic findings manifesting as
spherical “coin” lesions in the lung periphery
62

58. 63
 The pulmonary clear cell tumor forms a
circumscribed mass <1 cm to 3 cm (rarely >5 cm),
with a pushing border
 Tumor often infiltrates between small airway
epithelia, especially on its periphery, and infiltrative
margin is not a sign of malignancy

59. MICROSCOPY
 Perivascular tumor cells may have radial
arrangement around lumen; epithelioid cells (closest
to vessel) and spindle cells (remote from vessel) with
clear to granular eosinophilic cytoplasm; small,
central, round / oval nuclei with small nucleoli; often
multinucleated giant cells
 May have malignant features with marked atypia,
mitotic activity and necrosis
64

60. 65
(A) Sharp demarcation to
lung tissue
(B) Tumor cells are epithelioid and
have eosinophilic to clear cytoplasm

61. 66
(C) Tumor cells clustered around
blood vessels
(D) Focal calcification and stromal
sclerosis can be present

62. PEComa-NOS
67

63. Excluding AML, LAM and Pulmonary
CCST
 Group of rare, morphologically and
immunophenotypically similar tumors arising at a
variety of visceral and soft tissue sites, termed as
‘Perivascular epithelioid cell tumors–not
otherwise specified’.
 These tumors arising at a variety of visceral
(commonly gastrointestinal, gynecologic, and
genitourinary) and soft tissue (commonly
retroperitoneal, abdominopelvic, and cutaneous)
sites has been collectively termed non-AML, non-
LAM, non-CCST PEComas; or PEComas other than
AML, LAM, or CCST; or PEComas–not otherwise
specified (PEComas-NOS).68

64. CYTOGENETICS
 Few cases of pecoma have been karyotyped
 A specific cytogenetic aberration has not been
identified
 The presence of a t(3;10), losses on chromosomes
19, 16p, 17p,1p, and 18p and gains on
chromosomes X, 12q, 3q, 5, and 2q
 Show rearrangement of the TFE3 gene and
expression of TFE3 protein by
immunohistochemistry
69

65. CLINICAL FEATURES
 PEComas-NOS reported in almost every body site
 The uterus is the most prevalent reported site of
involvement
 Virtually arise in any age, peak in 4th decade
 F:M-7:1
70

66. PATHOLOGIC FEATURES
 Grossly, circumscribed, tan to gray with variable firm
and friable areas
 Tumor size- 4-6 cm
 Cut surface -white-tan to gray red, myxoid with focal
areas of hemorrhage and necrosis
 Biphasic tumors with epithelioid and spindle cell
components
71

67. 72
The cut surface has a variegated appearance, including focal areas of necrosis
SOFT TISSUE PEComa

68. Pecoma of soft tissue composed
predominantly of nests of epithelioid
cells with cleared out cytoplasm
73
Higher magnification of nests of
epithelioid cells in pecoma of
soft tisssue

69. 74
Cells with spindled morphology
in a soft tissue PEComa
Soft tissue PEComa with uniform
appearing nuclei

70. 76
(A,B) A mesenteric example with spindled cells and partly clear cytoplasm. Focal
nuclear atypia is present.
(C,D) A pelvic PEComa that also involves a lymph node. The tumor is composed
of spindled cells with mildly eosinophilic to clear cytoplasm and vessel walls with
sclerosis

71. 77
A malignant PEComa of the thigh contains significant mitotic activity
and bizarre multinucleated giant cells

72. Highly cellular smears in a malignant pecoma
78

73. HMB-45 immunoreactivity
79
Nuclear immunoreactivity for MiTF

74. 80

75. D/D:
81
 Gastrointestinal stromal tumor (GIST)
 Clear cell carcinomas (e.g., cervix, vagina, renal cell
carcinoma) - express cytokeratins
 Leiomyosarcomas

76. 82

77. 83

78. 84

79. REFERENCES:
85
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