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TIMELY REVIEWS

Section Editor: Zubair Baloch, M.D., Ph.D.

Psammoma Body:
A Product of Dystrophic Calcification or of a
Biologically Active Process That Aims at Limiting
the Growth and Spread of Tumor?
Dilip K. Das, M.B.B.S., M.D., Ph.D., D.Sc., F.R.C.Path*

Psammoma bodies (PBs) are concentric lamellated calcified Psammoma bodies (PBs) are concentric lamellated calci-
structures, observed most commonly in papillary thyroid carci- fied structures, called so because of their resemblance to
noma (PTC), meningioma, and papillary serous cystadenocarci-
noma of ovary but have rarely been reported in other neoplasms grains of sand, and are said to represent a process of dys-
and nonneoplastic lesions. PBs are said to represent a process trophic calcification, in which the deposition occurs
of dystrophic calcification. Despite numerous ancillary studies locally in nonviable or dying tissues with normal serum
over a span of three and half decades, formation of PBs remains levels of calcium and in the absence of derangements in
a poorly understood mechanism. Ultrastructural study of PTC calcium metabolism.1 In cytologic preparations, these cal-
has shown that thickening of the base lamina in vascular stalk
of neoplastic papillae followed by thrombosis, calcification, and
cosperites are 50–70 lm in size, round shaped with a
tumor cell necrosis leads to formation of PBs. Studies on serous glassy appearance, and stain dark-blue to black (Figs. 1A
cystadenocarcinoma of ovary and meningioma, however, and B) in Geimsa-stained and brown to black (Figs. 2A
revealed that collagen production by neoplastic cells and subse- and B) in Papanicolaou-stained smears.2 PB is observed
quent calcification was responsible for the formation of PBs. most commonly in papillary thyroid carcinoma (PTC),
The existence of some precursor forms of PBs was reported in
meningiomas and more recently in PTC, which were mostly in
meningioma, and papillary serous cystadenocarcinoma of
the form of extracellular hyaline globules surrounded by well- ovary.3 In PTC, paraffin sections of 40–50% cases4 and
preserved neoplastic cells or in a smaller number of cases intra- fine-needle aspiration (FNA) smears of 11–35% cases5
cytoplasmic bodies liberated from intact tumor cells. Cellular contain PBs. Meningiomas (45%)6 and one-third of serous
degeneration and necrosis, leading to the disappearance of neo- cystadenocarcinomas of ovary7 also show PBs. PBs have
plastic cells, were noticed by us only around PBs but not around
the precursor forms. Based on the above findings, it is suggested
been reported rarely in other neoplasms, viz, insulinoma,8
that rather than being the outcome of dystrophic calcification of lactotrope adenoma of pituitary,9 serous papillary ade-
dead or dying tissue, PBs may indeed represent an active bio- noma of borderline malignancy of the broad ligament,10
logic process ultimately leading to degeneration/death of tumor uterine serous carcinoma,11 endocervical adenocarci-
cells and retardation of growth of the neoplasm. It may also noma,12 cholangiocellular carcinoma,13 chromophobe re-
serve as a barrier against the spread of neoplasm. Diagn. Cyto-
pathol. 2009;37:534–541. ' 2009 Wiley-Liss, Inc.
nal cell carcinoma,14 psammoma carcinoma of the perito-
neum,15 and a number of benign non-neoplastic condi-
Key Words: psammoma bodies; papillary thyroid carcinoma; tions including colloid goiter and Hashimoto’s
meningioma; serous cystadenocarcinoma thyroiditis.16–22 In a study by Khoo et al.,23 29 (59.2%)
of the 49 patients with ultrasonographic (US) evidence of
intrathyroidal calcifications, had PTC and 12 of the
Department of Pathology, Faculty of Medicine, Kuwait University, remaining 20 cases had MNG in histology. Since 24% of
Kuwait the histologically confirmed PTC cases in their material
*Correspondence to: Dilip K. Das, M.B.B.S., M.D., Ph.D., D.Sc., had benign cytologic diagnosis, these authors23 suggested
F.R.C.Path., Associate Professor, Department of Pathology, Faculty of
Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. that surgery should be recommended in a solitary thyroid
E-mail: dilip76@hotmail.com nodule with evidence of calcification regardless of FNA
Received 15 December 2008; Accepted 11 February 2009 cytologic findings because of the high risk of malignancy.
DOI 10.1002/dc.21081
Published online 16 April 2009 in Wiley InterScience (www. In the process of dystrophic calcification, single ne-
interscience.wiley.com). crotic cells constitute seed crystals that become incrusted

534 Diagnostic Cytopathology, Vol 37, No 7 ' 2009 WILEY-LISS, INC.


Diagnostic Cytopathology DOI 10.1002/dc
PSAMMOMA BODY

Fig. 1. A: Papillary thyroid carcinoma (PTC): FNA smear from a 2 3 2-cm solitary isthmic nodule in a 32-year-old woman shows a bluish-black
psammoma body with concentric lamellations (MGG, 3400). B: PTC: FNA smear from a 3 3 3-cm solitary nodule in the right lobe of the thyroid in
a 38-year-old woman. Smear shows sheets neoplastic cells with intranuclear cytoplasmic inclusions and an irregular deposit of small rounded calcific
bodies (MGG, 3400). C: PTC with an adenoid cystic pattern: FNA smear from a solitary cold nodule in the right lobe of thyroid in a 35-year-old
woman, Smear shows precursors of PBs in the form of laminated hyaline globules, surrounded by neoplastic cells (MGG, 3200). D: PTC: FNA smear
from diffuse thyroid swelling in a 22-year-old man. Smear showed psammoma bodies (represented by unstained areas) and precursor hyaline globules
(MGG, 3200). E: PTC with a significant tall cell component (10–29% tall cells): FNA smear from a 2 3 2 3 1.5 cm. heterogeneous, solid, right-lobe
solitary thyroid nodule in a 53-year-old woman. Rare intracytoplasmic hyaline globule (arrow) is seen (MGG, 3400). Inset: multiple small, laminated
intracytoplasmic hyaline globules (MGG, 31000). F: PTC: U.S-guided FNA smear from a 1.5 3 1-cm solitary cold nodule in the left lobe of thyroid
in a 40-year-old woman. Smear shows numerous intracytoplasmic, magenta colored targetoid, globular bodies in the neoplastic cells. One such body is
coming out of the cell (arrow) (MGG, 31000). Inset: one isolated tumor cell with a cytoplasmic magenta colored inclusion body (MGG, 31000).
[Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

with the mineral deposits and the progressive acquisition capillaries and degenerative cells as initiators of the for-
of outer layers may create its lamellated configurations mation of these calcareous bodies. Tubuchi et al.,26
giving rise to PBs.1 According to Majno and Joris,24 dys- immunohistochemically demonstrated IgG in blood ves-
trophic calcification has two major phases, viz, initiation sels, whorls, and PBs in meningiomas, and suggested the
(nucleation) and propagation, which can occur intracellu- possibility of a humoral immune reaction in regard to
larly or extracellularly, whereas initiation of intracellular whorl and PB formation but there appears to be no further
calcification occurs in the mitochondria of dead or dying studies in this front to ascertain their views. The notion of
cells, initiators of extracellular calcification include phos- dystrophic calcification influenced the interpretation of
pholipids found in the membrane bound vesicles, which most of the findings on PBs in a number of studies.25,27,28
are about 200 nm in diameter. After analyzing compo- According to LiVolsi,4 true PBs apparently are formed
nents of PBs in meningiomas, Creda-Nicolas25 considered by focal areas of infarction of the tips of papillae,

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Fig. 2. A: Metastatic adenocarcinoma: pleural effusion sample from a 30-year-old woman who had bilateral pleural effusion and left supraclavicular
lymphadenopathy. The smear shows a large sheet of malignant cells with many psammoma bodies. A few papillary/ball-like cluster of malignant cells
were also present in the smears (Papanicolaou stain, 3 100). B: Metastatic papillary adenocarcinoma: asitic fluid sample from a 60-year-old woman
who presented with massive ascites. Both ovarian carcinoma and lung carcinoma were considered clinically. Smear from ascitic fluid shows two PBs
among malignant cells in papillary clusters (Papanicolaou stain, 3 400). C: Papillary thyroid carcinoma (PTC): FNA smear from a 4 3 3-cm solitary
cold nodule in the right lobe of thyroid in a 27-year-old woman. Smear shows fusion of four PBs and a separate single PB in the tip of a papillary
frond (Papanicolaou stain, 3 400). D: PTC: Another part of the papillary cluster shown in Figure 2C. Numerous degenerated/pyknotic neoplastic cells
are observed around PBs (Papanicolaou stain, 3 200). E: PTC: FNA smear from a 3 3 3-cm solitary nodule in the right lobe of thyroid in a 38-year-
old woman. Smear shows a papillary frond along with a PB in the core and scattered degenerated/pyknotic nuclei among neoplastic cells (Papanicolaou
stain, 3 200). F: PTC: another microscopic field from the case shown in Figure 2E. Smear shows a papillary frond without PB and four PBs with very
few or no neoplastic cells surrounding them (Papanicolaou stain, 3 400). [Color figure can be viewed in the online issue, which is available at www.
interscience.wiley.com.]

presumably due to thrombosis of the delicate vessels or Pathogenesis of PBs in the Neoplasms
damage as a result of minimal trauma, but they are differ- Most of the works on pathogenesis of PBs have been
ent from dystrophic calcification, which tends to be irreg- done in meningiomas. As early as 1961, Klose29
ular or jagged and rarely shows lamellations. A pertinent described the significance of relation between elastic
question is, if PB is not an example of dystrophic calcifi- fibers, blood vessels, and PB formation in meningiomas.
cation, what is the mechanism of its formation? Further- Virtanen et al.,30 in a scanning electron microscopic
more, since both PB and irregular calcification may exist (SEM)-based study of PBs in meningiomas, observed that
in the same tumor as has been reported in some PTC the PBs were spherical rather than tubular three-dimen-
cases,5 do they represent two different pathogenetic mech- sional structures, with undulating surface of the body,
anisms or can be explained by a single process? covered by interwoven fibers; in cross section, these

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Diagnostic Cytopathology DOI 10.1002/dc
PSAMMOMA BODY

bodies had a lamellar internal structure with concentric et al.36 followed all stages of PBs formation at the submi-
strands and fibers with associated bidlike material. These croscopic level. These investigators36 observed that PBs
investigators30 concluded that the structure of PBs seen in are formed as a result continuous deposition of microcrys-
SEM speaks in favor of its genesis by calcification of tals of oxyapatites on accumulations of protein substances
concentrically deposited fibrillar extracellular material. in ergatoplasms cysterns and on mitochondrial cristae,
According Kubota et al.,31 this mineralization process giving rise to intracytoplasmic inclusions. After conflu-
may represent a certain dystrophic calcification of menin- ence, these inclusions fill the cell resulting in cell death
gocytic cells. Taking into consideration the presence of and liberation of small PBs. Much later, Kiyozuka et al.37
remnants of degenerated cells, matrix vesicles and giant found that BMP-2 and type-IV collagen-producing slow-
bodies with or without mineralized deposits in the peri- growing tumor cells most likely form PBs in ovarian can-
vascular area of meningioma, this group of authors28,32 cer. Yamashima et al.38 found that membrane-free matrix
suggested that the formation of PBs in the meningocytic granules, which were also present together with a small
whorls may represent degeneration in some central cells. number of membrane bound matrix vesicles and matrix
Subsequently, matrix vesicles and matrix giant bodies minerals in the villous microcores in the human arachnoid
derived from the degenerated cells sequestrate hydroxyap- villi, may serve as principal calcification nidi of PBs.
atite crystals and extension of this mineralization process According to them,38 the possible mechanisms of matrix
to surrounding connective tissue fibers gives rise to PBs. granule biosynthesis are extrusion of preformed arachnoid
After analyzing the components of PBs in meningioma cell structures or secretion of fine granular material with
and other elements of the tumor, such as capillaries and its extracellular assemblage.
degenerative cells that have been classically considered as On the basis of the ultrastructural study of thyroid PBs
initiators of the formation of these calcerous structures, in the tumor and nontumorous areas, Johannesen and
Creda-Nicolas,25 however, concluded that the mineraliza- Sobrinho-Simoes,27 suggested that PBs probably represent
tion of the PBs is induced principally by the collagen the end stage of two biologic events: (i) thickening of the
fibers synthesized by the menigocytes and that the form base lamina of the vascular stalk of the neoplastic papil-
of mineralization is spherical and growth is radial, con- lae, followed by vascular thrombosis, calcification, and tu-
trolled by the tumor cells. Tsuchida et al.33 found that mor cell necrosis and (ii) necrosis and calcification in
PBs in meningiomas arise due to collagen production by intralymphatic tumor thrombi in the thyroid adjacent to
tumor cells followed by obliteration and disappearance of the tumor or in the opposite thyroid lobe. In a PTC case
tumor cell processes. Kubota et al.34 also observed sub- diagnosed by FNA and confirmed by histology, Haji
stantial amount of collagen fibers within large PBs but et al.39 observed rare PBs but many laminated hyaline
did not elaborate on the source of collagen. According to globules (HGs) giving rise to an adenoid cystic pattern
these authors,34 whereas matrix vesicles, presumably pro- (Fig. 1C). von-Kossa stain on paraffin section revealed
duced by meningothelial cells, may serve as initial nidi of positively stained rings of calcium in these HGs, which
calcification, collagen as well as elastic fibers, which lay were immunohistochemically negative for thyroglobulin.
adjacent and parallel to the apatite crystals in the menin- Based on morphological features and histochemical/im-
gocytic whorls, may play an important role in orienting munohistochemical reactions, these authors39 suggested
crystal deposition during growth of extracellular PBs and that these hyaline bodies may be the initial or precursor
serve as early sites of calcification. stage of PBs. Following this, we (Das et al.)5 reviewed
Ferenczy et al.,35 through transmission electron micros- the FNA cytologic material of PTCs diagnosed during a
copy studies on PBs in benign and malignant papillary se- period of 3 years and found extracellular precursor forms
rous ovarian neoplasms, observed that the formation of for calcifications, which included laminated large HGs
PBs is initiated intracellularly, in both neoplastic epithe- (Fig. 1D), small HGs, branching hyaline cylinders, and
lial cells and stromal histiocytes and provided supportive irregular hyaline deposits. These precursors forms were
evidence to the concept that PBs in ovarian papillary se- present in a significantly higher number in PTC (33.3%)
rous neoplasms are a consequence of dystrophic calcifica- when compared with follicular neoplasm (0.0%, P ¼
tion associated with cellular degeneration. According to 0.0142) and among PTC cases with PB/irregular calcifica-
these authors,35 the initial seeding site of apatite crystals tion (80.0%) than to those without PBs (22.7%, P ¼
is served by lipid-rich intracellular vesicles, which are 0.0012). Subsequently, taking into consideration the views
derived from dehiscent tumor tissue and autophagocytosed expressed by Kozlovskii et al.36 regarding intracellular
by tumor cells and heterophagocytosed by histiocytes, and formation of PBs in serous adenocarcinoma of the ovary,
large extracellular PBs result from fused calcific bodies, we re-examined our PTC cases and found intracellular
which have been extruded from calcified cells. In a light bodies resembling precursors of PBs (Fig. 1E and inset)
microscopic and ultrastructure study of serous adenocarci- in four (7.4%). These structures were possibly interpreted
noma of the ovary published in late 1970s, Kozlovskii as intracytoplasmic colloid inclusions during initial exam-

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ination of smears. All these four cases had precursors of deposited irregularly in the stroma, giving rise to irregular
PBs in extracellular locations and one of them had PBs calcification.
also. In a recently reported case, we40 demonstrated
numerous intracytoplasmic targetoid bodies in a case of
PTC and their release from well-preserved tumor cells PBs in Non-Neoplastic Conditions
(Fig. 1F and inset), suggesting that precursor substances PB has been described in benign non-neoplastic condi-
for calcification can be formed intracellularly, and the cal- tions such as endometrium,22 Hashimoto’s thyroiditis,19
cification in PTC need not necessarily be taking place and multinodular goiter or benign hyperplastic thyroid
over nonviable and dying cells. Almost a decade before, nodules.16–18 Dugan et al.19 concluded that PBs may be
we described precursors of PBs in PTC, Tsuchida et al.33 seen in any benign process, such as nodular goiter or lym-
had described similar precursors in meningiomas as round phocytic thyroiditis, that produces reactive papillary
bodies with concentric laminations like a transversely cut hyperplasia of the thyroid epithelium. However, it has
onion at light microscopic level, and ultrastructurally been pointed out that the hyperplastic papillae, although
these bodies were composed mainly of collagen fibers similar to neoplastic papillae, lacks a central stromal
that emerged from surrounding tumor cells. Nakayama core,43 which is important for formation of PBs in our
et al.41 also reported a case of papillary adenocarcinoma view. Could these PBs then represent left over material or
of sigmoid colon with PBs in the stroma and intracyto- remnants of neoplastic papillae, which once existed in
plasmic HGs of varying sizes (3–30 lm in diameter) in these benign lesions? It is known that there is a signifi-
the tumor cells at the tip of papillary structures and su- cant association between Hashimoto’s thyroiditis and PTC
perficial areas of the tumor, which were PAS and as revealed from thyroidectomy specimens44,45 and high
PTAH positive but negative for a-1-antitrypsin, a-1- prevalence of RET, RAS, and ERK expression in both the
antichymotrypsin, lysozyme, HCG, and AFP. However, lesions.46 In a study by Fink et al.,47 71 cases (16.7%) of
according to these authors,41 both PBs and HGs repre- occult micropapillary carcinoma were observed among
sented degenerative change of neoplastic cells and PBs 425 thyroid diseases other than carcinoma of follicular
in their case originated from single necrotic tumor cells, cell derivation, which included 317 nodular hyperplasia,
upon which successive layers of calcium salt were 36 thyroiditis, 44 follicular adenomas, and 28 others.
deposited. Yamashita et al.48 also reported a high prevalence of thy-
It is obvious from the aforesaid observations on menin- roid cancer associated with adenomatous goiter (30.7%),
giomas, serous adenocarcinoma of the ovary, and PTC, and their result suggested that a considerable number
that controversies regarding the pathogenesis of PBs and (137 of 256) of associated carcinomas remained occult.
the nature of their precursors are far from over. According According to these authors,48 the detection of calcification
to LiVolsi,4 the pathogenesis of PBs in PTC is regarded in the thyroid gland is one of the surgical indications for
as a poorly understood mechanism. Javonovic et al.42 also patients with adenomatous goiter. In a report by Hunt and
felt that the origin of PBs, one of the choroids plexus Barnes,49 the clinical, pathologic, and follow up informa-
aging changes, remains an enigma for the scientists till tion in the study of 29 patients with nontumor associated
date. From review of literature, we have observed that PBs in thyroid or perithyroidal lymph nodes revealed a
papillae formation is an important morphologic feature in contralateral or an ipsilateral tumor in 27 cases, of which
most of the neoplasms associated with PBs. Taking into the majority (20 cases) was PTC. These authors49 recom-
consideration our own findings and those of others, it is mend that thyroid glands with nontumor associated PBs
suggested that PB usually starts as precursor forms in the and no histologically identified carcinoma be entirely sub-
cores of papillary fronds. These precursor forms are com- mitted to identify any microscopic carcinoma.
posed of collagen fibers and membrane-bound vesicles
secreted by tumor cells, which are laid down in alternate
concentric layers. The alternate rings of von-Kossa posi- PBs in Serous Effusions
tive material in the precursor bodies, demonstrated by us,5 Parwani et al.50 reported PBs in 123 (3.7%) of 3335 body
possibly represent the layers containing matrix vesicles cavity fluids samples. All 11 pleural and pericardial fluid
undergoing calcification. Thus, the deposition of collage- samples were malignant (carcinoma of the thyroid, lung,
nous materials and membrane bound vesicles in alternate and ovary) compared with 62 (55.4%) of 112 ascitic fluid
concentric layers in the papillary fronds and their subse- samples (carcinoma of the ovary, uterus, and mesothe-
quent calcification leading to the formation of PBs may lioma); in 9 of the remaining 50 cases of benign perito-
be a histologic (anatomical) compulsion, as is the case of neal fluid samples, malignancy was demonstrated on fol-
formation of epithelial pearls in invasive keratinized squa- low-up tissue biopsy. These findings strongly link PBs
mous cell carcinoma. When there are no preexisting pap- with malignancies having papillae as an important mor-
illary fronds, the material secreted by PTC cells may be phological feature.

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PSAMMOMA BODY

PBs in Cervicovaginal Cytology rous tumors. The authors57 could morphologically trace
PBs in cervicovaginal cytology specimens are associated the transit of these PBs and their associated cytologically
with benign and malignant conditions.51 Of the 31 women benign tumor cells through the entire female genital tract.
with PBs in cervicovaginal cytology described by Mis- Residual neoplastic cells are sometimes observed inti-
draji et al.,51 19 had benign outcome and 12 had malig- mately associated with PBs in PTC.4 As early as 1959,
nant neoplasms. Parkash and Chacho52 detected PBs in Klink and Winship58 indicated that PBs in PTC represent
the cervicovaginal smears of 20 patients (0.009%) among dead papillae or ‘‘tomb stones’’ marking the place where
82,840 smear examination during a period of 5 years and papillae existed. It is suggested that the deposition of col-
9 of these 20 cases were associated with malignancy (six lagen and concentric calcification in the central vascular
uterine serous/clear cell carcinoma, two serous ovarian core may lead to compromise in nutrient supply to the tu-
carcinoma, and one fallopian tube carcinoma). In a study mor cells resulting in their degeneration or necrosis and
of 34,814 cervicovaginal smears during 4 years, Zreik and disappearance (Figs. 2C–F). This may be one of the rea-
Rutherford53 detected PBs in 18, which included 8 post- sons behind finding of PBs in Hashimotos thyroiditis and
menopausal cases and of them, 7 had gynecologic malig- colloid goiters, in areas away from the tumor mass in the
nancies (five with uterine serous/clear cell carcinoma, one organs affected by PTC, endometrial carcinoma and other
ovarian serous carcinoma, and one serous carcinoma of neoplasms, and absence of neoplastic cells in lymph
the fallopian tube). Fadare et al.,54 who found 140 cases nodes with PBs. The indolent course4 and excellent progno-
with PBs in cervicovaginal smears in a review of world sis associated with PTC59 and the better prognosis of psam-
literature, concluded that the finding of PBs in this setting moma carcinoma of ovary and peritoneum15,59–61 can be
was distinctly unusual with an incidence of less than attributed partly to the degeneration and necrosis of tumor
0.001% on consecutively screened smears. There was cells following the formation of PBs, which may also act as
association of malignancy or ovarian borderline tumor in a barrier against their spread. Kuhn et al.59 described psam-
0–22.7% (up to 38%, when small series and case reports moma carcinomas of the ovary as slow-growing tumors as
and small series were included). revealed from DNA flow cytometry study; the estimated 5-
year survival for these tumors was 50%, as opposed to 10%
Explanation for Nontumoral PBs and Presence of for other tumors. According to these authors,59 the majority
PBs Outside the Tumor Mass of studies on psammoma carcinomas of the ovary consider
Valicenti and Priester55 reported a PB in the cervical PBs to be the result of tumor regression, associating the
smear of a woman on oral contraceptive and identified occurrence of PBs with longer survival.
other PBs and amorphous calcified structures as embed-
ded structures within the stroma. Among 11 benign cases Ancillary Studies That Explain the Process and
with PBs in the cervicovaginal smears descried by Par- Purpose of PB Formation
kash and Chacho,52 four had h/o oral contraception. Fau- The ultrastructural study of meningiomas during 1980s
sett et al.56 described PBs in 11 endometrial biopsies with and 1990s supported the concept that collagen and
benign findings as incidental findings. Ten of these 11 vesicles secreted by tumor cells formed PBs.25,28,31,33
women were postmenopausal and underwent endometrial Similar view is also expressed in a study involving ovar-
biopsy for abnormal uterine bleeding while using com- ian cancer.37 It is known that the presence of extracellular
bined hormonal replacement. According to Valicenti and matrix proteins between tumor cells is necessary to regu-
Priester,55 these endometrial changes (PBs) are thought to late their growth and differentiation. In an immunohisto-
be caused by the combination oral contraceptive agent. chemical study of PTC, whereas type IV collagen was
Cameron and McCluggage11 described wide-spread exten- localized in the basement membrane of vessels and partly
sive psammomatous calcification of the uterine leiomyo- in tumor cell nests, and extensive immunoreactivity for
mata, the myometrium and the cervical stroma in a case procollagen III peptide (PIIIP) was observed in cancer
of uterine serous carcinoma with bilateral ovarian metas- cells and fibroblasts in all the neoplasms, especially in
tasis. According to these authors,11 the presence of PBs is cases having fibrosclerosing stroma and or those showing
probably related to serous carcinoma, raising the possibil- extensive local invasion.62 These findings indicate that
ity that PB formation in serous carcinoma is the result of stromal collagen in PTC can be produced not only by
a factor secreted locally by the tumor, rather than the fibroblasts but also by tumor cells, and its productivity
widely held theory that their formation is secondary to ne- could be affected by the degree of tumor invasion.
crosis, with subsequent dystrophic calcification within a Thus, PB, which is largely thought to be the outcome
papillary neoplasm. Qazi et al.57 described the presence of dystrophic calcification over dead or dying tissues,
of numerous PBs in the cervical smear, endometrilal cur- may indeed represent an active process involving secre-
ettage, and peritoneal wash specimens from a patient with tion of collagen and membrane bound vesicles in alternate
subsequently discovered bilateral, ovarian, borderline se- layers by neoplastic cells and the calcification of vesicles,

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