Monsel's solution-induced artifact in the uterine cervix

Mark Spitzer, M I ) , a and Ann E. Chernys, MD b

Jamaica, New York

We documented and quantified Monsel's solution-related artifacts after cervical biopsies. All loop electrosurgical cone biopsy specimens over a 3-month period were reviewed for necrosis artifact of the surface epithelium. The degree of change was quantified and correlated with the antecedent use of Monsel's solution. Twenty-four cone biopsy specimens were evaluated. Three of the eight cone biopsy specimens obtained fewer than 10 days after the use of Monsel's solution showed definite changes. Between 10 and 18 days after the use of Monsel's solution, four of eight specimens showed change. After 18 days, none of eight specimens showed change. One specimen at 18 days showed focal changes that seemed to be related to the use of an unusually large amount of Monsel's solution, because the patient had had six biopsies within 2 days. The routine use of Monsel's solution may interfere with the ability to recognize and characterize disease process in cone biopsy specimens when the cone procedure is done within 3 weeks after the use of Monsel's solution. (Am J Obstet Gynecol 1996;175:1204-7.)

Key words: Monsel's solution, artifact, cone biopsy

Monsel's solution (ferric subsulfate) is a topical agent that is commonly used after mucosal biopsies, such as cervical biopsies, to achieve hemostasis. It is widely be- lieved to be a totally innocuous agent, and possible ad- verse effects have not been addressed in the gynecologic literature. However, there have been reports in the der- matologic and pathologic literature describing coagula- tion necrosis, macrophages, and fibroblasts with atypical nuclei and some foreign body inflammatory reactions in response to Monsel's solution) ' 2

Changes at our hospital led to markedly reduced wait- ing periods in the colposcopy clinic between diagnosis and treatment. Shortly thereafter, we began noticing extensive necrosis artifact on specimens from loop elec- trosurgical excision procedures done in our clinic. These findings were out of proport ion with our previous ex- perience. Some degree of cautery artifact is expected at the cut margin of the cone specimen because of the nature of the excision procedure. However, such histo- logic changes on the surface epithelium were considered highly unusual. This report documents the findings, ex- plores the likely cause of the problem, and quantifies its occurrence. Suggestions are made on how to prevent it.

Material and methods

All cone biopsy specimens obtained by loop electrosur- gical excision in our clinic over a 3-month period, from

From the Departments of Obstetrics and Gynecology and Pathology, b Queens Hospital Center affiliated with the Mount Sinai School of Medicine. Received for publication February 21, 1996; revised April 25, 1996; accepted May 17, 1996. Reprint requests: Mark Spitz~ MD, Department of Obstetrics and Gy- necology, Queens Hospital Center, 82-68 164th Street, Jamaica, NY 11432. Copyright © 1996 by Mosby- Year Book, Inc. 0002-9378/96 $5. O0 + 0 6/1/75028

March 1991 through May 1991, were reviewed by a single pathologist with specific attention to evidence of necrosis artifacts. The dates of the loop excision and the preced- ing colposcopically directed biopsy were recorded. In each case hemostasis was achieved after the colposcopi- tally directed biopsy with thickened Monsel's solution. Monsel's solution was applied sparingly with a cotton- t ipped applicator. The number of colposcopically di- rected biopsies was also recorded. All specimens were stained with Prussian blue stain to identify iron, to see whether the presence of iron correlated with the cautery artifact, and to see whether normal specimens lacked iron staining. The degree of change in each specimen was recorded and correlated with the interval from colpo- scopic biopsy to loop excision and the number of biopsies done.

All histologic changes were limited to the epithelium and superficial stroma. They ranged from coarsely granu- lar brown pigment within stroma and giant cells to ho- mogenization, granularity, and smudging of epithelium and superficial stroma (Fig. 1). In all cases the changes were sharply demarcated. The brown cast seen on he- matoxylin and eosin-stained specimens was demon- strated to be iron positive (Fig. 2). A diagnosis was ren- dered in all cases by comparison with the appearance of the epithelium in uninvolved areas. However, when dif- fuse changes were observed, the epithelium in >50% of the specimen blocks could not be evaluated. This was well beyond the biopsy site. The changes in the remaining positive cases were deemed focal. When the epithelium was involved, there was total loss of cellular detail that was quite distinct from changes resulting from cautery (Fig. 3) rendering evaluation of that focus impossible. Results of iron staining were negative in cases designated nega- tive or equivocal and negative for areas showing cautery artifact.

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Volume 175, Number 5 Spitzer and Chemys 1205 AmJ Obstet Gynecol

Fig. 1. Stroma depicted shows loss of detail and several well-defined foreign body giant cells (arrow).

Fig. 2. Darkly staining surface epithelium is stained by Prussian blue, confirming iron positivity. Sharp demarcation (arrow) between stained and unstained areas is characteristic.

Results

Twenty-four cone biopsy specimens were evaluated in the study interval (Table I). Two of those showed diffuse changes, and five showed focal changes. The changes in

two specimens were equivocal, showing only hemosid- erin-laden macrophages. Three of eight specimens from

patients whose loop excisions were done <10 days after the use of Monsel's solution showed definite changes (two diffuse and one focal). Between 10 and 18 days, four of eight loop excision samples showed focal changes. After 18 days, none of eight specimens showed changes. At 18 days the specimen from one patient showed focal changes; however, this patient had a total of six biopsies 2 days apart, and the total amount of Monsel's solution applied was higher in this case than in the others.

Comment

Monsel's solution is used routinely as a hemostatic agent in obstetrics and gynecology practice. The mecha-

nism by which it exerts its effect is thought to be the oxidizing capacity of the subsulfate group [O (SO4) 5] and

its low pH (-1), which aids in denaturing and agglutinat- ing proteins. Its possible adverse effects have not been addressed in the gynecologic literature. The dermato- logic literature does report that Monsel's solution can cause pigmentation of the skin. Davis et al. 2 noted that when Monsel's solution was applied to the uterine cervix it penetrated denuded mucosa and produced coagula- tion necrosis to a maximum depth of 0.6 mm. The acute necrotizing effect persisted for up to 2 weeks. Because their study was done on large specimens, they thought

1206 Spitzer and Chernys November 1996 Am J Obstet Gynecol

Fig. 3. Photomicrograph on left shows surface epithelium lacking detail, with only pyknotic debris rather than nuclei. Arrow indicates junction with unremarkable endocervical mucosa. This is contrasted with example of cautery artifact (right), which shows streaming cells and distinct although elongated nuclei. This specimen lacks homogenized appearance and iron positivity.

Table I. Evaluat ion of his tologic changes i n d u c e d by Monse l ' s solut ion

Patient No. Time interval (days) Histologie changes

1 6 Diffuse 2 6 None 3 6 None 4 7 Hemosiderin laden macrophages only 5 7 Diffuse 6 7 Equivocal 7 8 Focal 8 8 None 9 13 Focal

10 13 None 11 14 None 12 14 Focal 13 15 None 14 15 Focal 15 15 Equivocal 16 18 Focal 17 19 None 18 20 None 19 20 None 20 21 None 21 21 None 22 23 None 23 26 Hemosiderin laden macrophages only 24 28 None

Biopsies (No.)

1 2 1 1 1 1 1 2 1 4 1 2 1 2 1

3+ 3? 3 2 2 3 1 3 4 3

Twenty-four patients underwent electrosurgical loop excision during the study interval. *Interval from preceding diagnostic biopsy to loop excision. tTwo sets of biopsies 2 days apart.

t ha t the effects of Monse l ' s so lu t ion at the biopsy site

would be easy to miss a n d tha t the rou t i ne use of Monse l ' s

so lu t ion would n o t in t e r fe re with the r ecogn i t i on a n d

charac te r iza t ion of epi thel ia l growth d i s tu rbances in

con iza t ion specimens, However, they specula ted t ha t the

basic disease process cou ld be obscu red if small p u n c h

biopsies were taken f rom sites at which Monse l ' s solut ion

h ad b e e n appl ied recent ly#

O u r f indings c o n f i r m e d the his tologic changes seen

af ter Monse l ' s solut ion appl icat ion, b u t we f o u n d tha t

even in cone biopsy spec imens the effects in t e r fe re with

the i n t e r p r e t a t i o n of the disease process in areas where

Volume 175, Number 5 Spitzer an6 Chemys q207 AmJ Obsmt Gyneco!

necrot ic change was observed. The difference in conclu-

sions between our findings and those of Davis et al. 2 may

be related to the fact that our biopsies were colposcopi-

cally directed and therefore more well localized to the

lesions. Alternatively, it is possible that our pathologists

routinely take more cuts of cone specimens or that we

used th ickened Monsel 's solution ra ther than the solu-

tion straight out of the bottle. Nevertheless, in 7 of 16

specimens obta ined in the first 18 days after the initial

biopsies some coagulat ion necrosis was found. In the first

7 days the change was sometimes so diffuse that it inter-

fered with p roper in terpreta t ion of the disease process.

Because cone biopsies are frequent ly done to exclude

invasive or microinvasive cancer, this Monsel 's effect can

adversely affect the t rea tment decisions for a patient.

Our conclusion is that the rout ine use of Monsel 's

solution has the potent ial to in terfere with the ability to

proper ly recognize and characterize the disease process

in a cone specimen when it is obta ined within 18 days of

the previous colposcopically directed biopsy and espe-

cially in the first 7 days. Because some degree of change

was seen in specimens f rom four patients between 14 and

18 days after the initial biopsies, it must be assumed that it

would take at least several more days for the effect to

clear. Therefore , if the clinician wishes to avoid the risk of

in te r fe rence with the in terpre ta t ion of a subsequent cone

biopsy by coagulat ion necrosis, cone biopsies should be

delayed for _>3 weeks (certainly no fewer than 2 weeks)

after the biopsy in which Monsel 's solution has been used

for hemostasis.

R E F E R E N C E S

I. Amazon K, Robinson MJ, Rywlin AM. Ferrugination caused by Monsel's solution. Am J Dermatopathol 1980;2:197-205.

2. Davis JR, Steinbronn KK, Graham AR, Dawson BV. Effects of Monsel's solution in uterine cervix. AmJ Clin Patho11984;82: 332-5.