Abril - 2017

adilha

CML

382

ssoc

ras

2017; 63(4):379-385

Microinvasive carcinoma represents the initial stage

of stromal infiltration by neoplastic cells that ruptured

the basement membrane, measuring up to 5 mm deep

and 7 mm wide in the underlying cervical stroma. How-

ever, it is only diagnosed microscopically.

8,25-27

From the

practical point of view, it is impossible in smears to ac-

curately ensure that a carcinoma lesion is microinvasive.

The cytological pattern may resemble a high-grade squa-

mous intraepithelial lesion or an invasive carcinoma. The

category of high-grade squamous intraepithelial lesion

with suspected invasion characteristics (Bethesda System)

or high-grade intraepithelial lesion, which cannot rule

out microinvasion (Brazilian Nomenclature for Cervical

Reports), can be applied when neoplastic cells in syncytial

clusters exhibit occasional nucleoli and parachromatin

clearing. Frankly invasive squamous carcinoma shows in

histopathological examination nests of neoplastic cells

infiltrating the stroma beyond 5 mm depth from the

basement membrane.

25-27

ifferential

diagnoses

cervical

cancer

In cervical neoplasms, differential diagnoses are essen-

tially made by a process of elimination.

26,27

The most com-

mon include:

•

Squamous intraepithelial lesions, especially keratini-

zing ones (absence of tumor diathesis, absence of

“clear spaces” in nuclei characterizing the irregular

distribution of chromatin, absence of nucleolus in

other non-keratinized abnormal cells).

•

Repair process (rare isolated cells, lower nuclear-cy-

toplasmic ratio, less significant abnormalities in ch-

romatin distribution, absence of tumor diathesis).

•

Atrophy (absence of irregularity in nuclear margins,

absence of irregularities in chromatin distribution).

•

Cytopathic changes by herpes virus (multinuclea-

tion, nuclear molding and chromatin rarefaction in

other cells).

•

Effect of radiotherapy/chemotherapy (macrocytosis,

polychromasia, cytoplasmic vacuolization, chroma-

tin with “blurred” appearance).

•

Poorly differentiated endocervical or endometrial

adenocarcinoma (glandular arrangements and sphe-

rical arrangements, columnar cells in endocervical

adenocarcinoma, frequent vacuolation and common

neutrophil infiltration in endometrial adenocarcino-

ma, sometimes eccentric nuclei, with less hyperchro-

masia and more frequent and prominent nucleoli,

absence of keratinized cells).

•

Metastatic adenocarcinoma (characteristics similar

to those described above).

26-29

ost

radiotherapy

effects

cells

Cellular and molecular changes induced by radiotherapy

include: nuclear DNA destruction or damage, inhibition

of protein synthesis, and denaturation/coagulation of

proteins. Normal cells are also compromised, resulting in

their death or in nuclear and cytoplasmic changes that

may persist for many years.

19,29,32,33

Cervical smear is con-

sidered an excellent method of investigation in the follow-

-up of patients undergoing radiation therapy for cervical

cancer. The finding of malignant cells that persist after

treatment or that reappear soon after allows immediate

clinical and/or surgical intervention before the onset of

any symptoms. It is important to note that after the begin-

ning of radiotherapy, during a period between four and

eight weeks, cervical smears will show abundant necrotic

material, with many inflammatory cells and occasional

malignant cells. Cytological examination, therefore, is not

indicated at this stage to assess whether the neoplasm

persists. After this period, all malignant cells disappear,

and an atrophic cytological pattern is established.

19,27,29,32,33

Cellular changes are related to both the acute and to the

chronic phases following radiation therapy. It is not always

easy to differentiate these changes from those of malignant

cells. On the other hand, a cytopathologist with little ex-

perience in this area may underestimate the changes, miss-

ing the opportunity to detect early or recurrent cancer.

19,29-31

Persistent or recurrent carcinoma is diagnosed in the

cervicovaginal smear when malignant cells are identified

in the course of radiotherapy or immediately after its

completion. It indicates radioresistance of the neoplastic

cells, being thus related to a poorer prognosis. Persistent

malignant cells exhibit, in addition to irradiation-related

alterations, others that are associated with malignancy.

Thus, in addition to pleomorphism and hyperchromasia

that are common in cells affected by irradiation, there is

thickening of the nuclear margins and a well-preserved,

coarse and irregularly distributed chromatin. Increased

nuclear-cytoplasmic ratio is also observed. The presence

of keratinized, pleomorphic cells may indicate malig-

nancy. The most reliable criterion to establish the viabil-

ity of neoplastic cells is the finding of mitoses.

26,27,34

Since radiotherapy is associated with characteristic

cytological changes, including nuclear activation, in-

creased cytoplasm (with preservation of the nuclear-cy-

toplasmic ratio), cytoplasmic vacuolization, eosinophil-

ia, polychromasia, multinucleated giant cells, nuclear

membrane blebbing and nuclear vacuolization, as well

as repair cells, atypical stromal cells, endothelial cells and

macrophages,

29,31,35

cytological samples should be col-

lected a few months after radiotherapy. However, it is