role of fine-needle aspiration cytology in evaluation of cutaneous metastases
TRANSCRIPT
Role of Fine-Needle AspirationCytology in Evaluation ofCutaneous MetastasesSonal Sharma, M.D.,* Mrinalini Kotru, M.D., D.N.B., Amit Yadav, M.D.,Manish Chugh, M.D., Anu Chawla, M.D., and Mani Makhija, M.D., D.N.B.
Skin is an uncommon site for metastasis. This study was done toevaluate the role of FNAC as an important tool for investigatingcutaneous and subcutaneous nodules in patients with knownmalignancy or as a primary manifestation of an unknown malig-nancy.
All the FNAC done from January 2003 to August 2008 werereviewed (n ¼ 55,556). Ninty-five patients (49 males and 46females with age range of 4–96 years) with cutaneous/subcuta-neous nodules which were diagnosed as metastasis were ana-lyzed. Primary tumors of skin/subcutis were excluded from thestudy.
In our study, 63 out of 95 cases had a known primary malig-nancy. Of these, five had underlying hematological malignancyand 58 patients had solid organ tumors. Lung carcinoma wasseen to metastasize most commonly to skin in males and breastcarcinoma in females. The most common site for a cutaneous/subcutaneous metastasis was chest wall [40 followed by abdomi-nal wall (14) and scalp (9)]. Multiple site involvement was alsoobserved (8). In 32 cases primary site was not known. Theywere most commonly diagnosed as poorly differentiated carci-noma followed by adenocarcinoma.
FNAC can diagnose a variety of tumors in the skin and supportthe diagnosis of a metastasis in case of a known primary andoffer a clue to underlying malignancy in case of an occult pri-mary. Diagn. Cytopathol. 2009;37:876–880. ' 2009 Wiley-Liss, Inc.
Key Words: cytology; cutaneous metastases
Cutaneous metastases are uncommon presentations of an
underlying malignancy. Data from autopsy series indicate
an incidence of 0.8%–4%.1 In most of the cases they
occur in patients known to have some malignancy. But
rarely, they may be the first manifestation leading to rec-
ognition of underlying condition on detailed investigation.
Most of these cases represent terminal phase of the dis-
ease. Therefore, it is appropriate to utilize fine-needle
aspiration cytology (FNAC) as a minimally invasive tool
for diagnosis in these cases, thereby, obviating the need
for a biopsy. Although, there are case reports in literature
on cutaneous metastases,2,3 the role of FNAC as an im-
portant tool for investigating these patients has been
reported in only a few studies.4–6
Therefore, this study was aimed to investigate cases
which presented with a clinical impression of cutaneous/
subcutaneous metastases from pre-existing tumors or as
the first manifestation of an unknown primary. The role
of FNAC in evaluating these cases was assessed.
Materials and Methods
This study is a retrospective study in which patients who
presented with palpable cutaneous or subcutaneous nod-
ules suspicious of being metastases were included.
Records of all the patients subjected to FNAC in the Uni-
versity College of Medical Sciences & GTB Hospital
between January 2003 and August 2008 were reviewed.
Of 55,556 cases reviewed, 95 cases diagnosed as cutane-
ous/subcutaneous metastasis were included in the study.
Cases with cutaneous nodules occurring at the site of pre-
vious surgery were excluded from the study. Cases sus-
pected as primary tumors of skin/subcutaneous tissue
were also excluded from the study.
FNAC was performed using a 22-gauge needle and 10-ml
disposable plastic syringe. Multiple passes were made in
the mass while maintaining negative pressure. Aspirated
material was used to prepare air-dried as well as alcohol-
fixed smears. Air-dried smears were stained by May–
Grunwald–Giemsa method. Alcohol-fixed smears were
stained using Papanicoloau method. Special stains like
Periodic acid Schiff (PAS) were performed if required.
Department of Pathology, University College of Medical Sciences,Delhi
*Correspondence to: Sonal Sharma, M.D., Reader, Department of Pa-thology, University College of medical Sciences, Shahdara, Delhi-110095. E-mail: [email protected]
Received 17 December 2008; Accepted 27 April 2009DOI 10.1002/dc.21119Published online 15 June 2009 in Wiley InterScience (www.interscience.
wiley.com).
876 Diagnostic Cytopathology, Vol 37, No 12 ' 2009 WILEY-LISS, INC.
Results
There were 95 patients with cutaneous/subcutaneous nod-
ules suspected to be metastases in whom FNAC was car-
ried out between January 2003 and August 2008. The
patients were represented by 49 males and 46 females
(M:F ratio ¼ 1.06:1). Age range was 4–96 years (Mean ¼62 years) in males and 16 to 80 years in females (Mean
¼ 51.5 years).
In 63 of these 95 cases there was a known primary
malignancy at the time of aspiration. Fifty-eight patients
had solid organ tumors and five had underlying hematolog-
ical malignancy. Table I shows the sites of metastasis and
FNA diagnosis in cases with known primary and solid
organ malignancy. Table II displays sites of metastasis and
FNA diagnosis in cases with known hematological malig-
nancy. In the rest 32 cases primary site was not known.
These were classified as cutaneous/subcutaneous metasta-
ses from an unknown primary as shown in Table III.
The commonest source of a known primary tumor was
breast (21) followed by lung (13), ovary, larynx, bone,
Table I. Cutaneous Metastases in Cases With Known Primary
S. No.Site ofprimary No. of cases Site of cutaneous metastasis FNA diagnosis
1 Breast 21 Chest wall (18), axilla (1),abdominal wall (2)
Infiltrating duct carcinoma (17), Poorly differentiatedcarcinoma (3), Invasive carcinoma with mucinousbackground (1)
2 Lung 10 Chest wall (4), arm (1), axilla (1),scalp (2), neck (1), multiple sites(1)
Adenocarcinoma (3), squamous cell carcinoma (3),poorly differentiated carcinoma (4)
3 Larynx 3 Neck (2), Back (1) Squamous cell carcinoma (2), poorly differentiatedcarcinoma
4 Bone 3 Leg (1), Shoulder (2) Ewing’s sarcoma/PNET5 Gall bladder 3 Chest wall (2), umbilicus (1) Adenocarcinoma6 Ovary 3 Chest wall (1), Umbilicus (1),
abdominal wall (1)Adenocarcinoma
7 Kidney 2 Back (1), multiple sites (1) Renal cell carcinoma8 Pancreas 2 Abdominal wall (2) Adenocarcinoma9 Stomach 2 Umbilicus (1), chest wall (1) Adenocarcinoma10 Thyroid 2 Scalp (1), chest wall (1) Follicular carcinoma11 Cervix 2 Chest wall (1), abdominal wall (1) Poorly differentiated carcinoma12 Periampullary 1 Abdominal wall Adenocarcinoma13 Oral cavity 1 Neck Poorly differentiated carcinoma14 Esophagus 1 Abdominal wall Adenocarcinoma15 Colon 1 Multiple sites Adenocarcinoma16 Prostate 1 Abdominal wall Adenocarcinoma
Total 58
Table II. Cutaneous Involvement in Cases With Underlying Hematological Malignancies
S. No. Hematological malignancy No. of cases Site of involvement FNA diagnosis
1 Chronic myeloid leukemia 2 Scalp (1), arm (1) Extramedullary hematopoiesis2 Multiple myeloma 2 Scalp (1), chest wall (1) Plasmacytoma3 Non-Hodgkin lymphoma 1 Chest wall Non-Hodgkin lymphoma
Total 5
Table III. Cutaneous Metastases in Cases with Unknown Primary
S. No. FNA diagnosis No. of cases Site of cutaneous metastases
1 Adenocarcinoma 12 Chest wall (5), abdominal wall (4), umbilicus (1),back (1), multiple sites (1)
2 Poorly differentiated carcinoma 15 Chest wall (5), abdominal wall (1), scalp (3), arm (1),back (1), forehead (1), shoulder (1), multiple sites(2)
3 Squamous cell carcinoma 1 Multiple sites4 Small round cell tumor possibly Ewing’s/PNET 2 Forearm (1), multiple sites (1)5 Small round cell tumor possibly neuroblastoma/Wilms 1 Scalp6 Poorly differentiated tumor possibly neuroendocrine 1 Abdominal wall
Total 32
FNAC OF CUTANEOUS METASTASES
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gall bladder, ovary, and kidney (Fig. 1). Overall the most
common site for a cutaneous/subcutaneous metastasis was
chest wall [n ¼ 40 (42%)] followed by abdominal wall
[n ¼ 14 (15%)] and scalp [n ¼ 9 (9%)]. Multiple site
involvement was also observed [8 cases, (9%)]. Chest
wall involvement was most frequently associated with
carcinoma breast (17 cases) and lung cancer (four cases)
due to proximity of these tumors. However, chest wall
involvement was not limited to these two primary sites
only. It was seen in many other malignancies of organs
like carcinoma ovary (Fig. 2), cervix, thyroid (Fig. 3) and
gallbladder.
Abdominal wall and umbilical involvement was almost
exclusively observed in intra-abdominal malignancies,
except for two cases of carcinoma breast. Another inter-
esting observation was that both cases in which thyroid
was the primary site, were follicular carcinoma.
In males the most common primary was from lung
while in females it was breast. The lung carcinomas
included adenocarcinoma (3), squamous cell carcinoma
(3) and poorly differentiated carcinoma (4). The breast
cancers comprised of infiltrating duct carcinoma (18)
(Fig. 4) and three cases of poorly differentiated carci-
noma. We also encountered 5 cases of hematological
Fig. 1. FNA smears of cutaneous deposits of renal cell carcinoma. MGG3200. [Color figure can be viewed in the online issue, which is availableat www.interscience.wiley.com.]
Fig. 2. Aspirate of subcutaneous nodule ovarian papillary carcinomafrom ascitic fluid tap site. MGG 3100. [Color figure can be viewed inthe online issue, which is available at www.interscience.wiley.com.]
Fig. 3. FNA smears from scalp swelling showing metastatic follicularcarcinoma thyroid. MGG 3200. [Color figure can be viewed in theonline issue, which is available at www.interscience.wiley.com.]
Fig. 4. Aspirate from chest nodule showing infiltratng ductal carcinomabreast. MGG 3400. [Color figure can be viewed in the online issue,which is available at www.interscience.wiley.com.]
SHARMA ET AL.
878 Diagnostic Cytopathology, Vol 37, No 12
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malignancies who presented with cutaneous/subcutaneous
nodules. These included previously diagnosed cases of
chronic myeloid leukemia (2 cases) (Fig. 5), multiple my-
eloma (2 cases) and non Hodgkin lymphoma (1 case).
The cytomorphology of aspirates in all these cases corre-
lated with the morphology of underlying hematological
malignancy. Most of these cases involved either scalp or
chest wall except one case which involved the arm.
There were 32 cases with unknown primary where cu-
taneous metastases were the first symptoms of disease.
They comprised of 19 males and 13 females (M:F ratio ¼1.5:1). The most common site for a cutaneous/subcutane-
ous metastasis in this group was also chest wall. The next
most common site was abdominal wall. Multiple site
involvement was also noted. The most common FNA di-
agnosis in this group was poorly differentiated carcinoma
(no further cytological diagnosis could be offered) fol-
lowed by adenocarcinoma and small round cell tumors
(Fig. 5). Immunochemistry was not available with us at
that time which could have helped to confirm the primary
tumor of origin.
Discussion
Skin is an uncommon site for development of metastases.
In a series reported by Saikia et al., out of a total 1022
metastatic malignancies at various sites, skin involvement
was observed in 58(5%) cases.7 In our series the incidence
of cutaneous metastasis was 0.17% (95/55556). In a similar
series by Gupta et al., an incidence of 0.5% was reported.
They had however, excluded pediatric age group in their
study.8 Furthermore, development of metastatic deposits in
skin indicates a very bad prognosis with rapid death. Cuta-
neous metastases from malignancy can arise either follow-
ing surgery or simultaneously with the tumor or first mani-
festation of unknown primary.6 They are mostly multiple
and rarely solitary. However in the present study, multiple
site involvement was seen in only 8 cases (9%). When soli-
tary, they may be confused with primary skin tumors.
They present as firm, nonulcerated skin nodules.9 The skin
metastases usually occur close to the site of primary tumor
for example chest in lung carcinoma, abdominal wall in
gastrointestinal tumors and lower back in renal cell carci-
noma.10 Tumor spread to regional skin is thought to be via
the lymphatics; subsequent spread to distant sites is due to
hematogenous spread.
The most common sites of metastases reported are
chest and abdomen, followed by head and neck.5,6 How-
ever in the present study the most common sites were
chest wall followed by abdominal wall and scalp. This
difference is probably due to larger number of cases from
lung and breast which are known to present with local
metastases via lymphatic involvement. The common
source of primary differs between the two sexes. In males
the most common sources are lung (25%), the large intes-
tine, melanoma, renal cell carcinoma and carcinoma of
the oral cavity.1,10 In our series, the most common pri-
mary in males was lung (10 cases) constituting 45% of
male patients with known primary. In females breast
accounts for large majority of cases (69%) followed by
lung, melanoma, kidney and ovary.1,10 In the present
study the most common source of primary in females was
also breast (21 cases), comprising 63% of female patients
with a known primary.
Cutaneous involvement in hematological malignancies
is a rare event. In the present study there were 5 such
cases. These included cases of chronic myeloid leukemia
(2 cases), multiple myeloma (2 cases) and non Hodgkin
lymphoma (1 case). FNA diagnosis was consistent with
the underlying hematological malignancy in all these
cases.
There were 32 cases in which there was no known pri-
mary at the time of FNAC. The overlying skin & underly-
ing muscle was normal and not fixed to the tumor.
Though it is difficult to differentiate metastatic adenocar-
cinoma from primary cutaneous adenocarcinomas, pres-
ence of pools of extracellular mucin, signet cells and
three dimensional papillae indicate metastasis rather than
primary lesion. On basis of these clinical features, multi-
plicity in few cases and morphology we suggested a diag-
nosis of metastasis. A definite primary could not be estab-
lished in these cases as they were lost to follow up.
Immunochemistry is known to be helpful in these cases in
identifying the primary tumor; however, it was not avail-
able to us at that time. Didolkar et al.11 and Osteen et
al.12 have reported that in many cases of cutaneous metas-
tasis, in spite of thorough clinical investigation and even
an autopsy, a primary may not be found.
Fig. 5. FNA smears from scalp swelling showing deposits of chronicmyeloid leukemia. MGG 3400. [Color figure can be viewed in theonline issue, which is available at www.interscience.wiley.com.]
FNAC OF CUTANEOUS METASTASES
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In conclusion FNAC is an invaluable tool by which
rapid diagnosis can be offered in cases presenting with
suspected cutaneous metastases. Similar views have been
expressed in previous studies also.4–6 If possible an
attempt to make a cell block should be made in these
cases. Immunohistochemistry can be performed on the
cell block to delineate the likely primary in cases with
unknown primary.
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