Psychotic depression due to giant condyloma Buschke

Rom J Morphol Embryol 2014, 55(1):189–195
CASE REPORT
RJME
Romanian Journal of
Morphology & Embryology
http://www.rjme.ro/
Psychotic depression due to giant condyloma Buschke–
Löwenstein tumors
ADELA MAGDALENA CIOBANU1), CAMELIA POPA2), MĂDĂLINA MARCU3), CONSTANTIN FLORIN CIOBANU4)
1)
Department of Psychiatry, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania; 1st Department of
Psychiatry, “Prof. Dr. Alexandru Obregia” Clinical Psychiatry Hospital, Bucharest, Romania
2)
“Constantin Rădulescu-Motru” Institute of Philosophy and Psychology of the Romanian Academy, Bucharest, Romania
3)
Department of Morphopathology, Ilfov Clinical Emergency Hospital, Romania
4)
Department of General Surgery, Ilfov Clinical Emergency Hospital, Romania
Abstract
A 63-year-old patient, with no psychiatric history, was admitted in the psychiatric department with depressed mood, loss of interest in
activities, apathy, insomnia, attention deficit, irritability, social withdrawal, prejudice and abandon delusions. Cerebral computed tomography
(CT) scan was normal but the general physical examination revealed a voluminous tumor in the inguino-pubic-ano-genital area measuring
350/80/40 mm, which appeared 15 years ago and grew gradually leading to local rickety hygiene and also to depression, especially in the
last time period when the tumor grew faster. The DSM-IV-TR diagnostic was affective disorder due to general medical condition. Surgical
exams concluded it was a giant exophytic tumor and was recommended a pre-operative abdominal CT scan, which did not revealed
metastatic spread. The treatment consisted in wide radical excision into the tumor-free resection margins. Anatomopathological exam
concluded condyloma acuminatum – Buschke–Löwenstein tumor (BLT), a very rare borderline tumor. In post-operative period, progress of
depression was spectacular, with the full mental recovery by decreasing the antidepressant and antipsychotic medication, fact that strengthen
the initial diagnostic of depression due to a general medical condition. Conclusions: Patients diagnosed with BLT may develop mental
disorders especially with devaluation and low self-esteem, social withdrawal and secondary functional impairment. Due to the malignancy
risk in such tumors and also the psychiatric unfavorable recovery prognostic in case of continuous general medical condition, the only
effective treatment is tumor resection with surgical, oncological, psychiatric postoperative revaluation.
Keywords: depression, surgery, Buschke–Löwenstein tumor, morphopathology.
 Introduction
Condyloma acuminatum or Buschke–Löwenstein
tumor (BLT) is a very rare tumor, generally presented in
case report, frequently located in the ano-genital region,
assuming that it appears secondary to a sexually
transmitted disease, destroying underlying tissue [1].
BLT is a locally destructive and infiltrative tumor,
cauliflower-like and it is thought to be induced by human
papillomavirus (HPV), most commonly HPV types 6
and 11 and occasionally types 16 and 18 [2–5].
It was first presented by Buschke in 1986, by Buschke
and Löwenstein in 1925, named by them “condyloma
acuminate carcinoma-like” of the penis [6].
Even though BLT has a histopathological benign
character, it has a malign behavior.
The verrucous carcinoma diagnoses can be difficult
due to the lack of malignant cytological characteristics,
especially if biopsy implies only the surface epithelium.
Therefore, large and deep biopsy is required, carefully
performed sections and detailed histopathological exams.
Verrucous carcinoma or Buschke–Löwenstein giant
condyloma may represent an intermediary stage between
penile condyloma and epidermoid carcinoma [7].
Usually, in the first line stands the excision surgical
exam, and the histopathological exam is absolutely
required to exclude squamous cell carcinoma for which
a radical aggressive surgery is mandatory [8].
ISSN (print) 1220–0522
The coexistence of BLT and squamous cell carcinoma
in the same site, changes the behavior and progress of
the lesion [9].
 Patient, Methods and Results
A 63-year-old patient, widowed, without psychiatric
history, brought by his family in psychiatric emergency
for depressed mood, delusional interpretation, apathy,
abolition, lack of interest, poor hygiene, irritability, heteroaggression, weight loss secondary to decreased appetite
and socially isolation. The patient lived alone for the last
10 years and the only treatment before admission was with
Verapamil 240 mg/day for paroxysmal supraventricular
tachycardia.
Family medical history and personal history did not
revealed something important. The patient does not
smoke, neither consumes alcohol or drugs.
At admission, the patient did not present hallucination,
only thought disturbances, especially devaluation and
incurability delusions with low self-esteem and also
persecutory and abandon delusions related to his daughter
who was living abroad for many years. The patients had
insomnia and irritability.
From the psychiatric point of view, the evaluation of
the depression stage was made through tracking the scores
obtained by applying the following scales: Hamilton
Depression Rating Scale (HDRS) – 17 items version,
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Adela Magdalena Ciobanu et al.
Global Assessment of Functioning (GAF) and Clinical
Global Impression Scale (CGI).
The patient’s mental status, functioning and global
clinical impression were evaluated by HDRS – 17 items
version, GAF and CGI. At admission, the HDRS – 17
items score was 29, GAF score was between 50–41,
indicating serious symptoms and serious occupational
and functional impairment (normal score 100). CGI score
was 5.
Patient’s state was evaluated at baseline and weekly,
for four months (including pre- and post-operative period).
We declared that the patient responded to treatment when
the HDRS score decreased at least with 50% toward the
baseline score, and fully recovery was declared when
HDRS score was ≤7.
Because of his old age and also the slightly spatial
disorientation, which afterwards was determined as being
apathy derived, the patient was neuro-cognitive evaluated
but the MMSE score and the watch test were normal.
Beside these scores, the dementia diagnostic was
excluded by performing a brain scan that was also normal.
Blood and urinary tests were normal. The results at
immunological tests anti-HIV1 and anti HIV2 were nonreactive. Syphilis tests: RPR (Rapid Plasma Reagin)/VDRL
(Venereal Disease Research Laboratory) were negative.
Neurological examination and EEG showed no
pathological elements, but the clinical examination
revealed a giant, cauliflower-like tumor, in the anal and
genital region, initially appeared 15 years ago, slow
glowing and progressive, with initial genital growth,
anal afterwards. The patient did not address oneself to a
doctor all these years, thinking that there is something
shameful, showing lately deteriorated mental status and
functionality, along with the significant increase in tumor
size.
Surgical and dermatological examinations concluded
that it is an ano-genital neglected tumor (causing serious
perianal hygiene problems).
It was observed serious impairment in the quality of
life because of poor hygiene in the ano-genital region and
also because of the depression due to medical condition.
For the psychiatric symptoms, we started the treatment
with Risperidonum 2 mg/day, Tianeptinum 12.5 mg three
times/day and Divalproex sodium 1000 mg/day. For
cardiac issues, the cardiologist maintained Verapamil at
the initial dose.
After several days of treatment, when the HAMD
score improved from 17 to 23 items, the patient was
transferred in the department of general surgery for tumor
therapeutic conduct, with organic affective disorder diagnosis
(DSM-IV-TR) and specialized psychiatric treatment.
Clinical examination revealed inguino-pubo-ano-genital
tumor, cauliflower, about 350/80/40 mm, large base of
implantation, irregular borders, color ranging from darkpurple to white-pink, surface with small areas of necrosis
overinfected, firm flesh (Figure 1).
The anal canal was carefully examined by rectal
examination and anoscopy and it was not involved by
the tumor invasion [10].
To evaluate the depth extension of the tumor and
any determinations, abdominal CT was performed. The
result of the CT scan was normal.
Figure 1 – Preoperative aspect
of the tumor. Inguino-puboano-genital tumor, cauliflower,
about 350/80/40 mm, large
base of implantation, irregular
borders, color ranging from
dark-purple to white-pink,
surface with small areas of
necrosis overinfected,
firm flesh.
There were no remote measurements of tumor data
and no extension in depth.
The main treatment was the total surgical excision of
the tumor in healthy tissue. The surgical excision is still
the first line of treatment for BLT, with a higher success
rate (63–91%) and lower risk of recurrence [7].
The surgery took place in two stages. In the first
stage was excised the right side of the tumor from the
right groin, pubic area, anal and perianal right region
and a part of right ischiorectal fossa (Figure 2a).
Intra-operative not found the deep invasion of the
lesion. Large sacrifice of tissue stretched around 0.5 cm
medial to the external anal sphincter to about 9 cm lateral
to it, and in about 4 cm of ischiorectal fossa tissue, also
being performed and takeoff 4–5 cm of skin-flap from
the right ischiorectal fossa to reduce tension in the suture.
In the second stage, was performed the excision of anoperianal outstanding tumor located at left (Figure 2b).
Surgery was performed under spinal anesthesia.
Figure 2 – Giant cauliflower tumors removed after
the first surgery operation (a) and after the second
surgery operation (b).
Post-operative evolution was favorable, except for
the occurrence of a dehiscence of the suture line
approximately 1.5 cm in both left and right, which was
cured per secundam in about 35 days (Figure 3).
Accurate diagnosis is on the biopsy and histological
examination.
Grossly examination shows a multi-fragment piece
355/79/38 mm, cauliflower aspect, irregular edges, hard
consistency, with small areas of necrosis overinfected,
color ranging from black-purple to white-pink.
Histopathological examination reveals massive
epidermal hyperplasia, hyperkeratosis and parakeratosis.
Part of keratinocytes shows keratinization but without
identifying keratin pearls (Figures 4 and 5).
Some keratinocytes had nucleus with prominent
nucleoli and large cytoplasm.
Keratinocytes with granular vacuolization, large
Psychotic depression due to giant condyloma Buschke–Löwenstein tumors
cytoplasm and nucleus with large prominent and visible
nucleoli are presented in Figure 6.
Lymphohistiocytic inflammatory infiltrate is often
present (Figure 7). Tumor cells have discrete cytoplasmic
nuclear atypia, but they were not detected in blood or
lymphatic vessels.
Are seen rounded masses that invade the dermis and
contiguous structures (Figure 8).
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Figure 3 – Three months postoperative image: inguino-pubogenital and ischiorectal region
with complete cure.
Figure 4 – Histopathological examination reveals massive epidermal hyperplasia, hyperkeratosis and parakeratosis:
(a) Papillomatosis florid area with hyperkeratosis. HE staining, ×40; (b) Epidermal papillomatosis, acanthosis,
hyperkeratosis. Koilocytic atypia. HE staining, ×100; (c) Epidermal papillomatosis hyperplasia and koilocytic atypia
present in the epidermis surface. HE staining, ×100; (d) Koilocytic atypia and dyskeratosis. HE staining, ×200.
Figure 5 – Massive hyperplasia of epidermis with endophytic growth, papillomatosis, koilocytic atypia and deep dermal
papillae with rounded contours: (a) Epidermal hyperplasia with hyperkeratosis, deep dermal papillae with rounded
contours. HE staining, ×40; (b) Massive hyperplasia of epidermis with endophytic growth. HE staining, ×100.
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Adela Magdalena Ciobanu et al.
Figure 5 (continued) – Massive hyperplasia of epidermis with endophytic growth, papillomatosis, koilocytic atypia and deep
dermal papillae with rounded contours: (c) Epidermal hyperplasia (acanthosis) and massive hyperkeratosis papilloma.
HE staining, ×100; (d) Epidermal hyperplasia, papillomatosis, koilocytic atypia. HE staining, ×200.
Figure 6 – Keratinocytes with granular vacuolization,
large cytoplasm and nucleus with visible nucleoli. HE
staining, ×100.
Figure 8 – Massive hyperplasia of the epidermis, with
rounded edges masses invading the dermis. Koilocytes
present. HE staining, ×100.
Condyloma acuminatum was excluded because histopathological images thickening of the stratum corneum,
endophytic increases and deeper invasion argues for
giant condyloma.
Microscopic images are suggestive for giant condyloma
of Buschke and Löwenstein.
Figure 7 – Epidermal hyperplasia and papillomatosis,
with the presence of lymphoplasmocytary inflammatory
infiltrate. HE staining, ×100.
In conclusion, clinical and pathological examination
revealed that it is a giant Buschke–Löwenstein tumor
(BLT), a rare tumor with an aggressive development by
growth and invasion of surrounding tissues.
Post-operative surgical, oncological and psychiatric
examinations showed that evolution was favorable.
Patient was evaluated weekly in first month and then
at two weeks to the end of four months of treatment.
Mental evolution was spectacular after surgery, so at
one-month post-operative the HDRS score decrease with
more than 50% compared with baseline.
After four month of treatment, final score for HDRS
was <7, CGI-S = 1, CGI-I = very much “improvement” at
endpoint compared to her condition at baseline (CGI-S =
CGI for severity of illness and CGI-I = CGI for
improvement), final GAF score = 100. All these results
concluded that our patient was normal, not at all ill and
he had a higher functionality with progressive and total
recuperation.
 Discussion
BLT is rarely, with an estimated incidence of 0.1%
in the general population and it is sexually transmitted
[3, 4].
Psychotic depression due to giant condyloma Buschke–Löwenstein tumors
The ratio between men and women is 3:1, BLT is
more common in men and the mean age of occurrence is
around 50 years. BLT can give recidivism and malignant
transformation. It is a tumor with broad-based implantation
and who can cause local destruction and infiltrative
phenomena [11–13].
Benign condyloma are usually caused by HPV types 6
and 11, whereas HPV types 16, 18, 31 and 33 are often
found in lesions with neoplastic transformation [14–16].
Besides those mentioned above, some authors consider
that precarious hygiene and promiscuity had incriminated
in causing BLT. Infection and viral factors also play
an important role in the etiology of BLT, such as
immunosuppression on HIV or HTLV-1, and chronic
infection, but also other factors such uncircumcised
patients, and relapsing genital warts [5, 17].
Death occurs in about 20% of patients. There have
been reported cases of malignant transformation of BLT
into squamous cell carcinoma, which can therefore show
metastatic spread [18].
In the case of our patient, the onset was in also in
genital area by papillomatosis injuries similar condyloma
acuminatum by, taking after 15 years of evolution the
appearance of inguino-pubo-ano-genital cauliflower tumor,
without deep invading and not gives the distance
impairments.
Because BLT is rarely, different types of treatment
are reported for giant condyloma. The type of treatment
depends on many factors, including the location of the
giant condyloma, how much invaded deep and surface,
the size, the unsuccessful previous therapies.
The literature describes other therapeutic methods
for the treatment of BLT. Thus, Tyring et al., in 1998,
describes a therapeutic solution with Podofilox solution
and gel like the first option of treatment for condyloma
acuminatum [19].
Also, it is described as a therapeutic method
cryotherapy by itself or in combination with topical 5Fluorouracil in relatively small BLT [20, 21].
There are authors who report cases successfully
treated with combination therapy, chemo-radiotherapy
[22, 23] and some cases in which surgical excision was
preceded by chemo-radiotherapy [24].
There have also been reported cases in which it
was used as a treatment for BLT, carbon dioxide laser
vaporization [25–28].
Studies have shown that regional radiotherapy is not
very useful since may induce undifferentiating of the
tumor cells, stimulating a rapid progression of the lesion
to the malignant degeneration [29–31].
The surgical excision is still the first line of treatment
for BLT with a higher success rate (63–91%) and lower
risk of recurrence [9].
In our case, the oncologist felt that the patient should
be monitored and reviewed regularly just for the moment
considering that total tumor excision was the best option
for treatment.
It is very interesting the impact of this disease on the
patient’s psyche and just slow growth over time, without
any pain in some patients, but also the feeling of shame,
make the disease was detected in the tumor stages reach
giant sizes.
193
In cases with painful tumor, the more it puts a
question, why these patients were not addressed from
time to a doctor, the more as condylomata are often
disfiguring and disrupt the patients sex life as they can
cause itching, burning, pain, and postcoital bleeding [1].
Accidental discovery of such a case in a psychiatric
department intrigued us to do a review of the literature,
which concluded there was no published articles focusing
on the impact on the functionality and the sexual life of
such a patient. Certainly, the impact can be expected to
be negative, but we did not find neither noting mentally,
social and family factors that led to lack of addressability
at a physician until the giant size of the tumor stages.
Thus, the reported cases we found that one patient
was homeless, another alcoholic [16], others were
diagnosed with HIV [2, 32]. In the case of our patient,
he was a widower for many years and lived alone.
Regarding the lack of addressability by a doctor, he said
he felt ashamed and guilty, which is why he did not want
his family to know the problem.
Other conditions: circumcised several years previously
for phimosis [33], immunosuppression in the case of a
young woman, which had been treated with electrocauterization for multiple small condyloma acuminatum
on the vulva and with approximately one month prior to
the relapse of the vulvar condylomata she had been
treated with high doses of systemic glucocorticoids for a
recurrent severe anaphylactic reactions [34].
Studies on the influence of clinical depression on
morbidity and mortality in oncology, as well as those
related to depression as a factor of malignancy are less
numerous, despite the high prevalence of depressive
disorder in patients with cancer.
However, it was shown that patients diagnosed with
depression before surgical management of malignant
brain astrocytoma have a lower survival rate than those
who had not pre-operative diagnosis of depression,
independent of the degree of disability, tumor grade and
ways of treatment [35].
At their turn, patients with breast cancer diagnosed
with depression have a high risk of mortality compared
to patients without depression [36]. This requires the
appropriate programs to reduce the depression before
and during treatment and after treatment [37]. Most
specialized studies also obviously the coexistence of
cancer and depression is associated with a significantly
increased risk of death, and the effect of depression on
the risk of death varies depending on the type of cancer
[38].
The correlation between depression scores in
patients with advanced cancer, calculated using the
Edinburgh Scale (EDS) and the risk of death was also
statistically significant, an increase of one point in EDS
score increased by 7% risk of death [39].
Most studies on depression cancer patients focused
on: improving quality of life; pathogenesis (immune
dysfunction may be a common pathogenic factor for
depression and cancer) [40, 41] screening tools available,
interference depression in cancer development that affect
adherence to treatment, immune and endocrine functions
[42] and specific treatment approaches [43–45].
Longitudinal studies on the presence of depression
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Adela Magdalena Ciobanu et al.
in cancer survivors were few and the association between
pre-operative depression and survival of patients require
further investigation. According to some of these studies,
the prevalence of depression was higher among survivors
of cancer of the stomach, even after treatment [46] and
fear of recurrence is a common concern of former
oncology patients [47]. Wide perineal excision with histopathological margins control is the best surgical choice
in the treatment of BLT if the anal canal is not involved
[48].
In our case, histopathological examination showed that
does not were still signs of malignancy of the tumor, which
made surgical excision only be the optimal method of
treatment, but because of the risk of malignancy of these
types of injuries, the patient will remain under regular
control made by oncologist, surgeon, psychiatrist and
psychologist to prevent tumor recurrence and secondary
depression.
[12]
[13]
[14]
[15]
[16]
[17]
[18]
 Conclusions
Larger studies are needed and a more detailed analysis
of psychological, social and environmental factors at future
cases reported with giant BLT. Our recommendation is
for the authors to stop more to the causes that led at so
late addressability to a doctor. Knowing the relationship
between depression and cancer, the patients with such
tumors must be regularly investigated after tumor excision
to treat any secondary depression because depression
persistent may increase the risk of malignancy existing
in this type of tumors.
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Corresponding author
Adela Magdalena Ciobanu, Lecturer, MD, PhD, Department of Psychiatry, “Carol Davila” University of Medicine
and Pharmacy, Head of 1st Department of Psychiatry, “Prof. Dr. Alexandru Obregia” Clinical Psychiatry Hospital,
th
10–12 Berceni Avenue, 4 Sector, 041915 Bucharest, Romania; Phone/Fax +4021–334 42 66/441, e-mail:
[email protected]
Received: August 21, 2013
Accepted: February 11, 2014