PRESENTATION

1. KCIAPM SLIDE SEMINAR
ANAND DIAGNOSTIC LABORATORY
ANAND DIAGNOSTIC LABORATORY
26/01/2014

2. CASE 1
35/F, LEFT HEMITHYROIDECTOMY
35/F, LEFT HEMITHYROIDECTOMY

3. GROSS APPEARANCE
GROSS APPEARANCE
Specimen of one lobe of thyroid measuring 3.5 x 2.0 x 2.5 cm
Cut section of the specimen showed nodule measuring 3 x 2 cm

4. MICROSCOPIC
MICROSCOPIC
Hypercellular nodules

5. Cellular area showing pleomorphism of follicular cells
with nuclear enlargement and hyperchromasia, and
with nuclear enlargement and hyperchromasia and
pale‐staining colloid

6. Cellular areas showing hyperchromatic nuclei

7. Hyperchromatic enlarged nuclei found at the edge of hyperplastic nodule

8. Differential diagnosis
Differential diagnosis
•
•
•
•
•
•
•
•
•
•
•
•
Follicular neoplasm with hurthle cell change
F lli l
l
ith h thl
ll h
Hurthle cell neoplasm of unknown malignant potential
Papillary carcinoma (Hurtle/Follicular variant)
Nodular hyperplasia
Nodular goitre with atypical adenoma
Dyshormonogenetic goitre
Oncocytic parathyroid adenoma with atypia
Nodular goitre with adenomatous hyperplasia and radiation
changes
h
Follicular adenoma with bizarre nuclei
Parathyroid adenoma
y
MNG with atypical adenoma
Hurthlized colloid adenoma with bizarre nuclei

9. DIAGNOSIS OFFERED
DIAGNOSIS OFFERED
Follicular neoplasm with Hurthle
changes
Hurthle cell neoplasm / Unknown
Hurthle cell neoplasm / Unknown
malignant potential
Papillary carcinoma (Hurthle /
Papillary carcinoma (Hurthle /
Follicular type)
Nodular hyperplasia
Why it is ruled out
No neoplasm, multiple
nodules, no capsule
No neoplasm, multiple
No neoplasm multiple
nodules, no capsule
No nuclear features
N
l
f
More colloid, should show
focal hyperplasia, no bizarre,
hyperchromatic nuclei.

10. Final diagnosis
Final diagnosis
• Dyshormonogenetic goitre

11. DIAGNOSIS
•
•
•
•
•
DYSHORMONOGENETIC GOITRE
DYSHORMONOGENETIC GOITRE
Hypercellular nodules with presence of cells
arranged in cords, microfollicular trabecular
di
d
i f lli l t b l
pattern.
Presence of pale staining colloid
Presence of pale staining colloid
Nuclear pleomorphism, hyperchromatic and
bizzare nuclei.
bizzare nuclei
Presence of pleomorphism at the edge of the
hyperplastic nodules and not in the entire gland.
hyperplastic nodules and not in the entire gland
Focal areas of fibrosis.

12. DYSHORMONOGENETIC GOITRE
DYSHORMONOGENETIC GOITRE
• Rare, inherited usually autosomal recessive disorder
• C i bl k i T3 /T4 th
Causing block in T3 /T4 pathway
• Defects involve
TSH unresponsiveness
TSH unresponsiveness
Defective iodine transport
Abnormal thyroid peroxidase
y
p
Formation of abnormal iodoprotein and defective
deiodination of monoiodotyrosine and diiodotyrosine
– Abnormal th roglob lin s ntheses and e cretion
Abnormal thyroglobulin syntheses and excretion
–
–
–
–
• Rarely associated with deafness (Pendred’s syndrome)

13. DYSHORMONOGENETIC GOITRE
DYSHORMONOGENETIC GOITRE
MICROSCOPIC
• Hypercellularity resulting from TSH stimulation of the gland
• Cellular nodules of trabeculae, cords, with solid or microfollicular pattern
of epithelial cells with pale colloid.
of epithelial cells with pale colloid
• May have papillary foci, marked cellular pleomorphism .
• Presence of pleomorphism at the edge of the hyperplastic nodules and
not in the entire gland.
not in the entire gland
• Mitosis, bizarre hyperchromatic nuclei are seen.
• True invasion is rare.
IMMUNOHISTOCHEMISTRY
• Thyroglobulin positive
• Calcitonin negative
Ref :Vittal S, Chandrasekaran M, Bijai Kumar K, et al.Dyshormonogenetic
Goitre. JR Coll Surg Edinb;1993;38:205‐207

14. CASE 2
40/F, MASTECTOMY SPECIMEN
/,
CLINICAL DIAGNOSIS OF PHYLLODES TUMOR

15. GROSS
Mastectomy specimen measuring 18 x 12 x 6 cm with
overlying skin measuring 15 x 10 x 2 cm
Cut section showed a grey white mass 16 x 10 x 8 cm
Cut section showed a grey‐white mass 16 x 10 x 8 cm
Areas of hemorrhage and cystic spaces

16. Tumour composed of multiple nodules, each representing a duct filled with
neoplastic proliferation.

17. MICROSCOPIC
Tumour arranged in solid nests ,sheets and cribriform areas.
Tumour shows pushing margins. Infiltration is noted in the muscle.

18. Papillary areas with hyperchromatic nuclei and increased N/C ratio

19. Foci showing lymphovascular emboli
Foci showing lymphovascular emboli

20. Focal clusters of foamy macrophages seen in this section
Focal clusters of foamy macrophages seen in this section

23. Differential diagnosis
Differential diagnosis
• Papillary carcinoma
ill
i
– ? Primary, ? Secondary
•
•
•
•
•
•
•
Papillary transitional carcinoma
p
y
Papillary carcinoma in situ
Micropapillary carcinoma with invasion
Invasive papillary carcinoma
Invasive papillary carcinoma
Adenomyoepithelioma
Malignant myoepithelioma
Papillary carcinoma with solid and papillary areas

24. DIAGNOSIS OFFERED
Papillary transitional cell carcinoma
Why it is ruled out
NO transitional type of epithelium as
described in literature. NO whorling or
streaming pattern.
Papillary carcinoma in situ
Usually resembles ordinary cribriform DCIS on
Usually resembles ordinary cribriform DCIS on
papillary stalks. Myoepithelial cells MAY be
present along stalks.
Micropapillary carcinoma with vascular
invasion
Shows fibrovascular cores. Psammoma
bodies not seen. Tubulo‐alveolar pattern NOT
seen.
seen
Invasive papillary carcinoma
Papillary carcinoma of breast tall cell
variant
Adenomyoepithelioma/ malignant
myoepithelioma
Papillary carcinoma with solid papillary
areas
NO “tall cells” seen. Nuclear criteria also not
fulfilled
Histology not consistent with diagnosis, 2
types of cells needed
types of cells needed

25. DIAGNOSIS
Solid variant of invasive papillary carcinoma
S lid
i t fi
i
ill
i
• Multiple nodules, each representing a duct filled
with neoplastic proliferation. Cells are ovoid to
with neoplastic proliferation Cells are ovoid to
spindle exhibiting solid pattern with fibrovascular
network.
network
• Other features observed were microcystic spaces
and foamy macrophages.
and foamy macrophages.
• Well defined pushing borders
• ER positive PR focally positive P63 negative
ER positive, PR focally positive, P63 negative.

26. SOLID VARIANT OF INVASIVE
PAPILLARY CARCINOMA
• A di ti t li i l tit
A distinct clinical entity .
• Controversial whether they could be considered
low–grade tumours
low grade tumours
• Originate from large or dilated ducts
• Pi
Primary affect older women occasionally seen in
ff
ld
i
ll
i
women below 50 years of age
• 90% il t l d i i th
90% unilateral and arise in the central area of the
t l
f th
breast
• Present with a bloody nipple discharge
Present with a bloody nipple discharge
• Nodular configuration and well circumscribed

27. SOLID VARIANT OF INVASIVE
PAPILLARY CARCINOMA
• Mi
Microscopically these tumours show multiple nodules,
i ll th
t
h
lti l
d l
each representing a duct filled with neoplastic
p
proliferation. Cells are ovoid to spindle exhibiting solid
p
g
pattern with fibrovascular network.
• Other features observed may be organoid pattern,
microcystic spaces and foamy macrophages
i
ti
df
h
• Well defined pushing borders
• Positive for ER and PR
Positive for ER and PR
• Negative for CK5/6.
• Other markers useful in diagnosis include Calponin
Other markers useful in diagnosis include Calponin,
P63, Skeletal muscle myosin heavy chain

28. References
References
• Tavassoli FA, Devilee P. World Health Organization
Classification of Tumours, Tumours of the Breast
and Female Genital Organs.2nd edition,Lyon
France: IARC Press.
• Gallager HS.Pathological types of breast cancer:
their prognosis.Cancer.1984;53:623‐629.
their prognosis Cancer 1984;53:623‐629
• Pettinato G, Manivel CJ, Panico L etal.Invasive
micropapillary carcinoma of the breast;Am J Clin
i
ill
i
f h b
Cli
Pathol.2004:121(6) 857‐866.

29. CASE 3
CASE 3
21/F, TOTAL THYROIDECTOMY SPECIMEN
21/F, TOTAL THYROIDECTOMY SPECIMEN

30. GROSS
Total Thyroidectomy specimen measuring 7 x 6 x 3.5 cm
Total Thyroidectomy specimen measuring 7 x 6 x 3 5 cm
Enlarged right lobe

31. GROSS
Cut section of right lobe shows friable pale brown
tumor measuring 4.5 x 3 x 3 cm

32. Area showing cribriform pattern with back‐to‐back follicles
g
p

33. Cribriform areas under higher magnification
Cribriform areas under higher magnification

34. Complex branching papillary structures lined by cuboidal cells
p
gp p
y
y

35. Focal areas showing squamoid nodules without evidence of keratinization
Focal areas showing squamoid nodules without evidence of keratinization

36. Areas showing lymphovascular emboli
Areas showing lymphovascular emboli

37. Differential diagnosis
Differential diagnosis
•
•
•
•
•
•
•
•
Mixed medullary and papillary carcinoma
Morular cribriform variant of papillary carcinoma
p p
y
Papillary carcinoma
Columnar cell carcinoma
C l
ll
i
Tall cell variant of papillary carcinoma
Papillary carcinoma follicular variant
Diffuse sclerosing
Diffuse sclerosing variant
Papillary variant of medullary carcinoma

38. DIAGNOSIS OFFERED
DIAGNOSIS OFFERED
DIAGNOSIS OFFERED
DIAGNOSIS OFFERED
Papillary cell carcinoma
Tall cell variant
ll ll
Diffuse sclerosing variant
Papillary variant of medullary
carcinoma
Papillary thyroid carcinoma‐
Cribriform morular (with foci of
C ib if
l ( ith f i f
tall cell variant )
Why it is ruled
Why it is ruled out
Nuclear features of PTC present.
However, doesn't satisfy criteria of 'tall
d
'
f
f ' ll
cells'
Lymphocytic infiltrate usually seen along
with other features with prominent
sclerosing areas.
Papillae are lined by multiple layers of
p
y
p
y
neoplastic cells with small and irregular
nuclei containing condensed chromatin.
Lack typical nuclear features of papillary
Lack typical nuclear features of papillary
carcinoma

39. DIAGNOSIS
Papillary Thyroid carcinoma (PTC) Cribriform morular
Papillary Thyroid carcinoma (PTC) Cribriform‐morular
variant.
• Complex branching papillae lined by cuboidal cells
Complex branching papillae, lined by cuboidal cells.
Nuclei are hyperchromatic, optically clear, with
longitudinal grooves .There is a blending of several
longitudinal grooves There is a blending of several
histological patterns .
• Cribriform areas with back to back crowding with
Cribriform areas with back to back crowding, with
arches of cells in the absence of intervening
fibrovascular stroma
fibrovascular stroma
• Solid areas consisting of morules of squamoid cells that
do not show any keratinization or intercellular bridges.

40. Papillary Thyroid Carcinoma
Cribriform‐Morular Variant
• PTC (C‐MV) is rare morphologic entity
• First described by Harach et al in association with FAP ( FAMILIAL
ADENOMATOSIS POLYPOSIS)
• Commonly seen in young females usually less than 30 years of
age
• Gross well circumscribed, somewhat lobulated mass, ranging
from 1.5‐2 cms in size. Sometimes show multiple satellite
from 1 5 2 cms in size Sometimes show multiple satellite
nodules
• PTC (C‐MV) carries a better prognosis than other aggressive
PTC (C‐MV) carries a better prognosis than other aggressive
variants of PTC ( tall cell, columnar, diffuse sclerosing and diffuse
yp )
follicular types)

41. REFERENCES
• Harach HR, Williams GT, Williams ED. Familial
adenomatous polyposis associated with thyroid
adenomatous polyposis associated with thyroid
carcinoma: a distinct type of follicular cell
neoplasm. Histopathology.1994;6: 549 561.
neoplasm Histopathology 1994;6: 549‐561
• Cameselle‐TeijeiroJ Chan JK Cribriform‐morular
Cameselle‐TeijeiroJ, Chan JK. Cribriform‐morular
vriant of papillary carcinoma; a distinctive variant
p
presenting the sporadic counterpart of familial
g
p
p
ff
adenomatous polyposis associated thyroid
carcinoma? Mod Pathol.1999;4: 400‐411.

42. CASE 4
CASE 4

43. CLINICAL PRESENTATION
 Female , 39 years old
 Complaints of fever and cough since 2 months
 P t hi t
Past history of pulmonary tuberculosis 4 years back
f l
t b
l i 4
b k

44. LAB INVESTIGATIONS
Bronchoscopy
Bronchial wash – AFB and cytology
CT scan
RML biopsy

45.  Bronchoscopy - mass occluding right middle lobe bronchus
 Bronchial wash – AFB – negative
Cytology – negative for atypical cells

46.  CT scan –
 soft tissue density mass measuring 5.4 x 5.7 x 5.8 cms in the right
middle lobe of lung in the perihilar region.
 Enlarged pretracheal and subcarinal group of lymph nodes
largest measuring 2.1 x 1.3 cms.
 Features suggestive of BRONCHOGENIC CARCINOMA with
metastasis to pretracheal and subcarinal lymphnodes.

47.  Biopsy –

Gross - grey white tissue fragment measuring 0.2x0.2x0.1 cms.
 Microscopy – small sized bland appearing tumor cells with
round to oval nucleus arranged in sheets and separated by
hyalinized stroma.
y
 I
Impression – F t
i
Features favoring a benign neoplasm of salivary
f
i
b i
l
f li
gland type; possibility of myoepithelioma is suggested.

50. PER‐
PER‐OPERATIVE
 Right posterolateral thoracotomy, bilobectomy and lymph
node clearance
 Per operative findings – hard mass measuring about 6 x 4 cms
in right middle lobe. Mutiple subcarinal and paratracheal
lymphnodes.

51. HISTOPATHOLOGY
Gross – right middle and lower lobes of lung. Tumor with pushing
margins in the middle lobe with occlusion of bronchus. Tumor
g
6 x 5 x 4 cms. Yellow white appearance.
dissection , largest node 2.5 x 1.0 x 0.5 cms.
Lymph node

56.  Microscopy  Tumor composed of squmaous cells, intermediate cells and
mucin secreting cells.
 All lymph nodes exhibit reactive changes
changes.

57. Bronchial lining

58. Adenoid cystic –
Adenoid cystic – like areas

59. Pleomorphic adenoma like areas

60. Squamous islands

61. DIFFERENTIALS
•
•
•
•
•
•
•
•
•
•
Large cell undifferntiated carcinoma
L
ll diff
ti t d
i
Large cell neuroendocrine carcinoma
Mucoepidermoid carcinoma
Squamous cell carcinoma
Lymphoepithelioma like carcinoma
Adenoid cystic carcinoma
Neuroendocrine tumor
Adenosquamous carcinoma
Ad
i
Adenoid cystic variant of diffuse malignant mesotheliomabiphasic type with ? Asbestosis
p
yp
Neuroendocrine carcinoma mixed variant

62.  Impression –
 low grade salivary epithelial neoplasm, ? Low grade
mucoepidermoid carcinoma , ? Pleomorphic adenoma.

63. IMMUNOHISTOCHEMISTRY
 Pan CK – positive in tumor cells
 S-100 – negative in tumor cells
 Vimentin – negative in tumor cells
 GFAP ( courtesy NIMHANS ) – negative in tumor cells
t
ti i t
ll

64. Pan CK

65. S 100

66. VIMENTIN

67. Final diagnosis
Final diagnosis
• Mucoepidermoid carcinoma of the lung – Low
g
grade

68. DISCUSSION
Rare primar tumor of lung – 0 1 – 0 2 %
primary t mor
l ng 0.1 0.2
Wide age range – mean age 40 years
Slow growing tumor
Main bronchus- submucosal glands of the
bronchus
• Classified under salivary gland neoplasms of
the lung
• Lobectomy, local resection or endoscopic
removal – excellent prognosis
• Diff
Differential di
ti l diagnosis iis adenosquamous and
i
d
d
adenocarcinoma of lung
•
•
•
•

69. REFERENCES
• Respiratory Medicine Case Reports 9
(2013) 18-20
• Arch Pathol Lab Med – Vol 131,
,
September 2007
• The new World Health Organization
classification of lung tumourE. Brambilla 1 , W.D.
Travis 2 , T.V. Colby 3 , B. Corrin 4 and Y. Shimosato 5ERJ
December 1, 2001 vol. 18 no. 6 1059 1068
December 1 2001 vol 18 no 6 1059‐1068

70. CASE 5
CASE 5

71. CLINICAL PRESENTATION
 Male 25 years old
Male,
 Mass per abdomen since 4 months
 Bilateral undescended testes
 Radiological finding – mass in right lumbar region measuring 20
x 20 cms. Extension upto liver superiorly pelvis inferiorly and
cms
superiorly,
crossing midline laterally.

72. PER OPERATIVE
 Persistant mullerian duct syndrome with left sided large
testicular tumor and right sided small testicular tumor

73. HISTOPATHOLOGY
 Gross – specimen altogether weighed 2140 grams and
measured 21 x 17 x 7 cms. Specimen consisted of a large, solid
pale brown tumor mass, spermatic cord, omentum and a
smaller tumor mass. Mid segment of spermatic cord showed a
g
p
nodular area measuring 2 cms.

77.  Microscopy –
 Features of classical seminoma in both nodular masses
masses.
 Adjacent testicular parenchyma from the smaller testicuar
mass exhibit features of intratubular germ cell neoplasia.
 Nodular area in spermatic cord exhibits endometrial glands ,
endometrial stroma and smooth muscle.
 Omentum exhibiting features of reactive mesothelial
hyperplasia.
h perplasia

78. ITGCN

79. Leydig cell hyperplasia

80. Seminoma ‐ classical

81. Seminoma

82. Endometrium + smooth muscle

83. DIFFERENTIALS
•
•
•
•
•
•
•
Leydig
L di cell h
ll hyperplasia with atrophic t b l and germ cell
l i
ith t
hi tubules
d
ll
tumor- seminoma
Persistent mullerian duct syndrome with seminoma and leydig
y
y g
cell hyperplasia
Persistent mullerian duct syndrome with cryptorchidism and
ITGCN and seminoma
Gonadal dysgenesis
True hermaphrodite
p
Anaplastic seminoma
Spermatocytic seminoma

84.  Impression –
 Classical seminoma – bilateral testes
 Intratubular germ cell neoplasia – right testis
 P i t t Mullerian duct syndrome
Persistent M ll i
d t
d

85. DISCUSSION
•
•
•
•
•
•
Rare form of male pseudohermaphroditisim ( 46 XY)
R
f
f
l
d h
h diti i
Persistence of mullerian duct structures due to lack of antimullerian hormone
X linked or autosomal recessive
Phenotypically male
Unilateral or bilateral cryptorchidism
15% risk of germ cell neoplasms and ITGCN

86. Case 6
CLINICAL DETAILS
• Male patient aged 37 years
• Fracture of L5 vertebra
• Blocks for opinion

92. Microscopy
• Tumor cells are polygonal to oval
• Arranged in distinctive organoid pattern
• Separated by fibrocollagenous stroma and
Sepa ated
b oco age ous st o a a d
surrounded by blood vessels

93. Initial diagnosis
• Neuroendocrine tumor

94. Differential diagnosis
•
•
•
•
•
•
•
•
•
•
•
Hemangioendothelioma
He angioendothelio a
PNET of vertebra
Mesenchymal chondrosarcoma
Angiomatous meningioma
Capillary hemangioblastoma
p
y
g
Paraganglioma
Epithelioid hemangioendothelioma
Metastatic RCC
Multiple myeloma
Metastatic carcinoma
carcino a
Telangiecatic Osteosarcoma

95. IHC
COURTESY - NIMHANS

96. SYNAPTOPHYSIN

97. CHROMOGRANIN - A

98. PARAGANGLIOMA

99. • Primary / metastatic
• No clinical evidence of primary
sweating, palpitations,
• No history of sweating palpitations hypertension

100. • Primary paragangliomas of craniospinal axis arise in
cauda equina
• Encapsulated intradural masses attached to filum
terminale or less commonly the spinal roots
• Functionally silent
• Erosion into the neighbouring bone
• Osseous metastases
• Good number of cases of primary paragangliomas of
the i l
th spinal canal have been published
lh
b
bli h d

101. Immunohistochemistry
• Chief cells - chromogranin, synaptophysin, neuron
specific enolase, serotonin, neurofilament and neural
ifi
l
i
fil
d
l
cell adhesion molecule
• S-100 protein negative

102. REFERENCES
1. Rosai J. Surgical pathology. 9th ed. 19(2): 2586 to 2587
2. Lmejjati M, Parker F, Lacroix C et al. “Paraganglioma of sacral spine”.
Neurosciences 2011;16(3):270-272.
; ( )
3. Shin JY, lee SM, Hwang MY et al. “ MR findings of spinal
paraganglioma:report of 3 cases”. J Korean Med Sci. 2001;16:522 6.
cases
Sci 2001;16:522-6
4. Moran Ca, Rush W, Mena H. “primary spinal paragangliomas:a
clinicopathological and immunohistochemical study of 30 cases .
cases”
Histopathology. 1997;31(2):167-173

103. CASE 7

104. CLINICAL DETAILS
• Female patient aged 56 y
p
g
years
• ? Ovarian mass
• Blocks for opinion
p

110. MICROSCOPY
•
•
•
•
•
•
•
•
•
Tumor with spindle cells
Hyalinized and oedematous stroma
Bizarre hyperchromatic nuclei
Clumped chromatin
Prominent nucleoli
Multinucleated forms
No necrosis
Occasional mitosis (0-1/10HPF)
Ovarian stroma not identified

111. Differential diagnosis
•
•
•
•
•
•
•
•
Embryonal carcinoma
E b
l
i
Sarcomatous variant of yolk sac tumor
y
Sarcomatoid transformation of stromal tumor
Fibrosarcoma
Poorly differentiated ovarian carcinoma
Angiosarcoma
Nodular fascitis
Leiomyosarcoma

112. •
•
•
•
•
•
•
•
Atypical bizarre cellular leiomyoma
Symplastic leiomyoma
Metastatic krukenberg tumor
Sex cord stromal tumor
Sclerosing stromal tumor of ovary
Endometrial stromal sarcoma
Malignant mixed mullerian tumor
Retroperitoneal Kaposi’s sarcoma

113. Signed out report
• Smooth muscle origin
• Benign nature
Symplastic leiomyoma

114. GROSS
1. Specimen of uterus cervix 8x3.5x3cm
p
E/S - Uterus – cauterized cavity
y
C/S – Endometrium – atrophic
Cervix – nabothian cyst
y
2. Irregular yellow tissue 4x3x3cm
C/S – Whorled appearance
Ovary not identified

121. Final diagnosis
Symplastic leiomyoma

122. • Atypical, bizarre, symplastic or pleomorphic
leiomyomas
• Spontaneously or in patients taking progestin
compounds
• Electron microscopy demonstrates actin filaments
with associated dense bodies as well as incomplete
basal lamina (features characteristic of smooth
muscle cells)
• Low risk of recurrence

124. REFERENCES
1. Rosai J. Surgical pathology. 9th ed. 19(2):1569-1636
2.
2 Fechner RE. Atypical leiomyomas and synthetic progestin therapy Am J
RE
therapy.
Clin Pathol. 1968,49:697-703

125. Case 8
Case 8
56/F, case of intermittent
painless hematuria.TURBT from
lateral wall of urinary bladder
l
l ll f i
bl dd

132. Differential diagnosis
Differential diagnosis
•
•
•
•
•
•
•
•
•
Lipoid variant of invasive urothelial carcinoma
Li id i t f i
i
th li l
i
Transitional cell carcinoma
Primary small cell carcinoma
Clear cell carcinoma
Malignant melanoma
High grade urothelial carcinoma
Neuroendocrine tumor of bladder
Metastatic RCC
Pigmented paraganglioma

133. Thought process
Thought process
• ??? Malignant melanoma

134. Perl s stain for iron
Perl’s stain for iron

135. Melanin bleach
Melanin bleach

136. HMB 45
HMB 45

137. Final diagnosis
Final diagnosis
• Malignant melanoma
– ? Primary
y
– ? Metastatic

138. Discussion
Discussion
• Primary melanoma of bladder is very rare
• 19 odd cases reported in literature
19 odd cases reported in literature
• Mostly metastatic from the skin or urethra

139. Criteria for primary melanoma of
bladder
• Ainsworth criteria
i
h i i
• Careful physical examination including the skin
p y
g
with Wood’s light together with detailed
y
history to exclude cutaneous melanoma
• Exclusion of visceral melanoma
• Pattern of recurrence consistent with primary
Pattern of recurrence consistent with primary
melanoma of bladder
• Histologically proved primary atypical
melanocytes

140. Treatment and prognosis
Treatment and prognosis
• R di l
Radical resection
ti
• Poor prognosis
• R f
References
•
•
•
•
•
•
•
Jalal Eddine El Ammari et al, “Primary malignant melanoma of the bladder,” Case reports in
urology,vol.2011
B. S. Stein and A. R. Kendall, Malignant melanoma of the genitourinary tract, Journal of
B S Stein and A R Kendall “Malignant melanoma of the genitourinary tract ” Journal of
Urology, vol. 132, no. 5, pp. 859–868, 1984. View at Scopus
A. M. Ainsworth, et al., “Primary malignant melanoma of the urinary bladder,” Cancer, vol.
37, no. 4, pp. 1928–1936, 1976. View at Scopus
B. Helpap, Nonepithelial neoplasms of the urinary bladder, Virchows Archiv, vol. 439, no. 4,
B Helpap “Nonepithelial neoplasms of the urinary bladder ” Virchows Archiv vol 439 no 4
pp. 497–503, 2001. View at Publisher ∙ View at Google Scholar ∙ View at Scopus
M. C. Wheelock, “Sarcoma of the urinary bladder,” The Journal of Urology, vol. 48, p. 628,
1942.
N. M. Anichkov and A. A. Nikonov, Primary malignant melanomas of the bladder, The
N M Anichkov and A A Nikonov “Primary malignant melanomas of the bladder ” The
Journal of Urology, vol. 128, no. 4, pp. 813–815, 1982.
C. T. Su and C. L. Prince, “Melanoma of the bladder,” The Journal of Urology, vol. 87, pp. 365–
367, 1962.

141. Case 9
Case 9
• Skin biopsy in a male patient
• Age not known
Age not known

145. Differential diagnosis
Differential diagnosis
•
•
•
•
•
•
•
•
•
Cutaneous mastocytosis
C t
t t i
Dermal nevus
Glomus tumor
Leukaemic infiltration
Cutaneous plasmacytoma
Lymphomatoid papillomatosis, DLE
???
Urticaria pigmentosa
pg
Metastatic cutaneous deposit‐ Adenocarcinoma

147. Final diagnosis
Final diagnosis
• Cutaneous mastocytosis

148. Cutaneous mastocytosis
• 80% of cases are urticaria pigmentosa
% f
i i i
• Mast cells
– 8‐15 microns in diameter
– Round or oval or fusiform in shape
Round or oval or fusiform in shape
– Granular cytoplasm
– Granules stain metachromatically with toludene
Granules stain metachromatically with toludene
blue or giemsa
– Granules are modified lysosomes containing
Granules are modified lysosomes containing
histamines and leukotrienes

149. Clinical symptoms
Clinical symptoms
• Release of histamines and leucotrienes
– Pruritis
– Itching
– Flushes
– Syncope

150. WHO classification of mastocytosis
WHO classification of mastocytosis
•
Cutaneous mastocytosis
– Maculopapular CM
– Diffuse CM
– Mastocytoma of skin
of skin
•
Indolent systemic mastocytosis(SM)
– Smoldering SM
– Isolated bone marrow mastocytosis
Isolated bone marrow mastocytosis
•
•
Systemic mastocytosis with an associated clonal hematological non‐mast
cell lineage disease
Aggressive systemic mastocytosis
Aggressive systemic mastocytosis
– With eosinophilia
•
Mast cell leukaemia
– Aleukaemic MCL
•
•
Mast cell sarcoma
Extracutaneous mastocytoma

151. Case 10
Case 10
• 34 yr old male
• Azoospermia for evaluation.
for evaluation.
• Left and right testicular biopsy was done

156. Gross
• Pale brown tissue bit measuring
0.6x0.3x0.3cm

157. Differential Diagnosis
Differential Diagnosis
Sertoli ll d l i t hi t ti
S t li cell nodule in atrophic testis.
Gonadoblastoma
Sex cord stromal tumor with annular tubules .
Testicular microlithiasis
Complete maturation arrest with corpora
amylacea and microlithiasis.
• Partial maturation arrest with testicular
microlithiasis
• Parasitic cysts
• ITGCN
•
•
•
•
•

158. Final diagnosis
Final diagnosis
• Hamartomatous nodule in probable Androgen
y y
insensitivity syndrome

159. Discussion
• Male AIS is a very rare disorder, affecting
fewer than 1 in 100,000 births
• Two types‐ complete and incomplete
• X li k d
X‐ linked male pseudohermaphroditism
l
d h
h di i

160. Statistics
• Affects 1 in 20,400 people
Affects 1 in 20,400 people
– 2/3 of cases inherited from mother
– 1/3 of cases come from a spontaneous mutation in
1/3 of cases come from a spontaneous mutation in
the egg
• No effect on life expectancy
p
y
• No racial differences
• A genetic condition where affected people have male
g
p p
chromosomes and male gonads with complete or partial
feminization of the external genitals
• An inherited X linked recessive disease with a mutation
An inherited X‐linked recessive disease with a mutation
in the Androgen Receptor (AR) gene resulting in:
– Functioning Y sex chromosome
g
– Abnormality on X sex chromosome

161. Androgen Receptor Gene
• AIS results from mutations in the androgen
receptor gene, located on the long arm of the X
chromosome (Xq11‐q12).
• The AR gene provides instructions to make the
protein called androgen receptor, which allows
cells to respond to androgens, such as
testosterone, and directs male sexual
d di
l
l
development.
• A d
Androgens also regulate hair growth and sex drive
l
l
h i
h d
di
• Mutations include complete or partial gene
deletions, point mutations and small insertions or
d l ti
i t
t ti
d
ll i
ti
deletions.

162. References
References
• 1991;10(2):126‐44.
• The androgen insensitivity syndrome
The androgen insensitivity syndrome
(testicular feminization): a clinicopathologic
study of 43 cases.
study of 43 cases
• Rutgers JL, Scully RE. University of California,
Los Angeles

163. •
•
•
•
•
•
•
Forty‐three patients with the androgen insensitivity syndrome (AIS), ages
Forty three patients with the androgen insensitivity syndrome (AIS) ages
14 to 83 (average 27) years, were studied.
Forty patients had complete AIS and three patients had incomplete AIS.
Microscopic examination of the testes revealed immature tubules, which
Microscopic examination of the testes revealed immature tubules which
contained rare spermatogonia in 28% of the cases.
Prominent Leydig cells and a spindle‐cell stroma resembling ovarian
stroma were found in a majority of cases
were found in a majority of cases.
The organization of the testicular parenchyma could be classified into one
of four patterns: diffuse tubulostromal, lobular tubulostromal, mixed
,
p
tubulostromal, or stromal‐predominant.
Hamartomas were present in 63% and Sertoli cell adenomas in 23% of the
cases.
g
p
p
p
Malignant tumors developed in 9% of the patients and comprised two
seminomas, one intratubular germ cell neoplasm with early stromal
invasion, and a malignant sex cord tumor

164. References
• Arch Pathol Lab Med‐ Vol 123, March 1999
• Ackerman’s Surgical Pathology, Male
Ackerman s Surgical Pathology, Male
reproductive system , Pg 1438‐ 1439

165. Case 11
Case 11
• 1 yr 4 months female baby presented with
chronic renal failure and failure to thrive
• Renal biopsy was sent for light microscopy and
immunofluorescence.
immunofluorescence

166. Gross
Gross
• Single linear grey brown tissue measuring 1.5
g
cm in length.

167. Immunofluorescence
• One core with 6 glomeruli, all of which are
g
g g g
q pp
negative for IgG, IgA, IgM, C3C, C1q, kappa
and lambda.

172. Differential diagnosis
Differential diagnosis
• C t lli
Crystalline nephropathy
h
th
• Crystalline nephropathy‐ post chemotherapy for leukemia /
lymphoma
y p
• Crystalluria – Urate
• Oxalosis
• Infantile nephropathic cystinosis
• Nephrocalcinosis
• T b l i t titi l nephritis associated with tubular necrosis
Tubulointerstitial
h iti
i t d ith t b l
i
• Nephrocalcinois
• Storage disease ?
Storage disease ?
• Multicystic renal dysplasia
• Nephronophthisis
p
p

173. Final diagnosis
Final diagnosis
• Chronic tubulointerstitial nephritis secondary
y
p
gy
g
to crystalluria morphology favoring Oxaluria.

174. Hyperoxaluria
• Urinary oxalate excretion that exceeds 40
i
l
i
h
d 0
mg/day.
• Primary ( rare genetic disease)
• Enteric
• Dietary
• Idiopathic or mild hyperoxaluria

175. Primary hyperoxaluria
Type I mutation of AGXT gene on chromosome 2 that codes for
alanine glyoxylate aminotransferase
alanine glyoxylate aminotransferase
Type II mutation of GRHPR gene on chromosome 9 that codes
Type II mutation of GRHPR gene on chromosome 9 that codes
for glyoxylate reductase and hydroxypyruvate reductase.

178. References
• Shekarriz B et al ; Hyperoxaluria ,emedicine,
p
Apr 2010
• Ackerman’s Surgical Pathology, Urinary tract,
Pg‐
Pg 1231
• Diagnostic pathology kidney disease , Colvin‐
Pg4‐ 106

179. Case 12…..

180. Lesion – below sinus lining…..

181. Lesion –nodules in a
p
pink stroma…..

182. Spindled stroma rich….

183. Nodules…..
Nodules
Large cells and…

184. Dirty looking “small cells”….

185. So…..
So
• Poorly circumscribed, submucosal lesion in
sinus
• Nodules + spindled stroma
• N d l
Nodules:
– large cells with prominent nucleoli
– Component of dirty looking small cells in
aggregates

186. Diagnoses…..
Diagnoses
•
•
•
•
•
•
•
•
Embryonal rhabdomyosarcoma ‐ 2
b
l h bd
Olfactory neuroblastoma‐ 2
y
Ganglioglioma ‐2
Astrocytoma ‐2
Astrocytoma 2
Carcinosarcoma ‐1
Rhinoscleroma ‐1
Melanoma 1
Melanoma ‐1
Ganglioneuroblastoma‐ 1

187. S100
Synatophysin
MIB‐1 (Ki67)

188. Synaptophysin‐ ganglionic element
S100 = schwannian componet
Small cells – very focal synapto+, high MIB = neuroblastic

189. So…..
So
•
•
•
•
Poorly circumscribed, submucosal lesion in sinus
Poorly circumscribed submucosal lesion in sinus
Nodules + spindled stroma
Stroma: schwannian (S100 pos)
Nodules:
Nodules:
– large cells with prominent nucleoli: ganglionic
(neuronal marker synaptophysin
(neuronal marker synaptophysin pos)
– Component of dirty looking small cells in aggregates
(neuroblastic: synapto focal pos, high MIB‐1)
(neuroblastic: synapto focal pos high MIB 1)
Ganglioneuroblastoma

190. Peripheral neuroblastic tumors
Not so grey….
•
•
•
•
Classification…….
Cl ifi i
Staging……
Risk stratification……
Closely related to the molecular/genetic
Closely related to the molecular/genetic
properties of the tumors of individual cases not –
tumor margins/necrosis/vascular invasion/
tumor margins/necrosis/vascular invasion/
spread…as in other tumors
Players….pathology…..behaviour (pathobiology…)

191. Q1: Where do they come from?
Q1: Where do they come from?
Neural crest = sympathetic nervous system
Neuroblasts, Ganglion cells, Schwann cells
Satellite cell
Ganglion cell
Nerve roots
Neck to pelvis……

192. Differentiate from ..for
confusion/clarity
• Peripheral
i h l
neuroblastic tumors
(pNTs)
( NT )
• neoplastic cells with a
neuronal phenotype
l h
• of neuronal (neural
crest) cellular origin...
t) ll l
i i
• deletion of
chromosome 1p and
h
1
d
MYCN amplification
• pPNET ( i h l
PNET (peripheral
primitive
neuroectodermal tumor)
• neuronal phenotype but
• of unknown (presumably
f k
(
bl
non‐neuronal) origin
• unique chromosomal
i
h
l
translocation fusing
EWS/ETS

193. How do they look?
International Neuroblastoma P th l
I t
ti
lN
bl t
Pathology Classification
Cl ifi ti
(INPC ‐ Shimada system)
• Four categories are discriminated according to the degree of
differentiation
[ganglionic cells 'organoid' maturation with the development
cells, organoid maturation with the development
of a Schwann cell stroma, and co‐existence of clones of
different maturity or of distinct aggressiveness]:
Neuroblastoma (Schwannian stroma‐poor)
(undifferentiated, poorly differentiated, dfferentiating)
Ganglioneuroblastoma intermixed (Schwannian stroma‐rich)
Ganglioneuroblastoma nodular
g
(composite Schwannian stroma‐rich/and stroma‐poor)
Ganglioneuroma (Schwannian stroma‐dominant)
(maturing, mature)
(maturing mature)

194. Neuroblastoma (poor diff), Neuroblastoma (differ), Neuroblastoma (undiff),
Ganglioneuroblastoma:
intermixed)
i t
i d)
Ganglioneuroblastoma:
nodular)
Ganglioneuroma:
Ganglion cells+ schwann cell)
Ganglion cells+ schwann cell)
Neuronal markers: Synaptophysin, NSE, MAP2, beta tubulin
Neuronal markers: Synaptophysin NSE MAP2 beta tubulin
Stroma – S100, GFAP

195. How do they behave? stratification….
How do they behave? stratification
• Clear stratification – “favourable”/
Clear stratification favourable /
“unfavourable” clinical/biological behaviors:
• Favourable (with/without treatment)
Favourable (with/without treatment)
– involution,
– spontaneous regression
spontaneous regression,
– tumor maturation,
• Unfavorable: OR aggressive progression
Unfavorable: OR aggressive progression,
• Closely related to the molecular/genetic
properties of the tumors of individual cases not –
i
f h
f i di id l
tumor margins/necrosis/vascular invasion/
spread…
d

196. How do they behave? stratification
How do they behave? stratification
• I t
International Neuroblastoma Ri k G
ti
lN
bl t
Risk Grouping,
i
INRG: Prior to any treatment patients will be put
into a risk category
into a risk category
• Favourable/unfavourable histology
– Age
– Mitosis/karryorhhexis index (MKI)
• Low: <100/5000 cells
/
• Intermediate: 100‐200/5000 cells
• High: >200/5000 cells
– DNA l id (FISH)
DNA ploidy
– MYCN amplification status

198. Why bother?...treatment
Why bother? treatment
• In European countries , the treatment of
i
h
f
neuroblastoma patients depends on
– age at diagnosis (below or over 1 year of age),
– extent of the disease (stage)
g
– a genetic parameter, i.e. the amplification of the
MYCN oncogene
• In United States and Australia, DNA Index of
the tumour cells and histopathology (INPC)
the tumour cells and histopathology (INPC)
are also included in therapy stratification

199. Mostly triploid
(FISH)
No structural
aberrations
•Surgery alone
•Standard
chemotherapy
h
h
Structural
aberrations
Two biological/clinical groups: DNA ploidy
Source: Atlas of cytogenetics in Oncology & Hematology
•Surgery alone
•Mutiagent
chemotherapy
•Myeloablative
M l bl ti
chemo with SCR
•External
radiotherapy
•MIBG…..

200. Bottom line….
Bottom line
• Our case
– Ganglioneuroblastoma, intermixed
g
,
– MKI: ?
– Favourable histology
Favourable histology

201. The Wrong Right
I screened the slide back and forth
As I peeked through the microscope
A furious looking cell stared at me
Eureka! I exclaimed with pride and glee
p
g
‘Carcinoma’ was my undoubted decree
My adamant colleague refused to agree
He made a mockery of my grey cell ability
As he dismissed my verdict with a tinge of hostility
‘Tis just a inflammatory cell, buddy
As benign as a dead flea!
My expertise doubted, my self‐esteem trampled
A severe blow to my medical arrogance
I took i up as a challenge
k it
h ll
My insult I needed to avenge
How can “I” be proven erroneous?
Both of us sought the counsel of Big Boss
Whose eyes can swoop on a cell like a hawk
I prayed my belligerent colleague be proven wrong
p y
y
g
g
p
g
And my joy knew no bounds
“It is malignancy” he assertively pronounced

202. My battered ego appeased
Out of the hospital stormed an egotist
Ecstatic at being proven a whiz
I deserved to treat myself to a drink
Three cheers for me –An adept pathologist!
On my way I glanced at the lady, frail and old
Awaiting her young son’s report with hope
I did not to notice her, of course
d d o o o ce e , o cou se
Coz I wasn’t going to be the one to give her the news
That her young son had only a few tomorrows
I sat in my car and pondered where to party that evening
But something gnawed at my heart; an intense aching
Hot Tears poured down my cheeks sans warning
Undid the façade I was sporting
The wee bit of a human hidden in me startled my being
Late into the sleepless night I had a dream
Big Boss admonished me, yet on my f
d
h d
face I saw a gleam
l
A single streak of the whitener fluid he drew
To erase my reporting and write one anew
Do early morning dreams really come true?
Reeta Subramaniam Mani

203. Thank you
Thank you