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the dilemma associated with the diagnosis of metastatic lesions with no obvious primary site has long been a challenge for the clinicians .
fine needle aspiration biopsy helps in confirming a clinical suspicion of local recurrence or metastasis of known cancer without subjecting the patient to further surgical intervention .
the present study was undertaken to ascertain the cytological diagnosis of metastatic lesions , with special reference to the clinicopathological analysis of the primary site in cases of epithelial and non - epithelial tumors .
the present study was conducted on 171 cases of metastatic malignancy , attending the inpatient and outpatient departments of radiotherapy and pathology of j.n . medical college , a.m.u .
all the cases underwent a basic evaluation consisting of history , physical examination ( including careful breast palpation and pelvic examinations in women and testicular and prostate examinations in men ) , laboratory studies ( including liver function tests and hemogram ) , chest radiography , computed tomographic ( ct ) scans of the abdomen and pelvis and mammography in women . when indicated by positive findings during this initial evaluation ,
these selective tests included sputum cytology , ct scan of the chest and gastrointestinal endoscopy .
all suspected metastatic lesions were subjected to fine needle aspiration biopsy ( fnab ) with a 22 - 23 g needle , and whenever necessary , under ultrasound and ct - guidance .
the smears were fixed in 95% alcohol and stained by hematoxylin and eosin ( h and e ) and papanicolaou stains .
histopathological examination was performed in 16 cases with inconclusive cytological impression after paraffin embedding and staining with h and e stain .
the majority of the cases , 81(47.4% ) , were observed in the fifth decade of life , followed by 76 cases ( 44.4% ) in the sixth decade and 11 cases ( 6.4% ) in the seventh decade of life .
however three cases were seen in the age group of 0 - 20 years , with a case of a 14 year - old girl with pleural and peritoneal effusions and diagnosed as metastatic juvenile granulosa cell tumor of the ovary .
another case of metastatic wilm 's tumor in a 3 year - old boy presenting with subcutaneous scalp swelling was observed by us .
observing the distribution of cases according to metastatic sites , the lymph nodes were the most frequent site , 115 cases ( 67.3% ) , followed by bone , 17 cases ( 9.9% ) , liver in 15 cases ( 8.8% ) and skin metastasis in 14 cases ( 8.2% ) [ table 1 ] . among the lymph nodes , the cervical group accounted for 65 cases ( 56.5% ) , followed by 31 cases ( 27.1% ) of axillary nodes .
primary tumor site and their respective metastatic sites the oropharynx , including the oral cavity and pharyngolarynx , was the most common primary site , 55 cases ( 32.2% ) , followed by a primary breast tumor in 38 cases ( 22.2% ) with 31 cases ( 81.6% ) metastasizing to axillary nodes .
primary in the gastrointestinal tract comprised 20 cases ( 11.7% ) , lungs 14 cases ( 8.2% ) and eight cases ( 4.7% ) each of primary tumor in the female and male genital tracts .
a total of 15 cases ( 8.8% ) studied by cyto - histopathology presented as metastatic cancer of unknown primary site [ table 2 ] .
distribution of cases according to the primary site in the cervical group of nodes , the predominant cytological diagnosis was squamous cell carcinoma , 56 cases ( 86.2% ) , with smears showing cohesive sheet of tumor cells with a high n / c ratio and nuclear hyperchromasia [ figure 1 ] , followed by adenocarcinoma in five cases ( 7.7% ) and four cases ( 6.1% ) of anaplastic carcinoma .
smear shows cohesive sheet of tumor cells with a high n / c ratio and nuclear hyperchromasia ( h and e 400 ) the axillary group was found to be the most important site of metastatic breast carcinoma in 31 cases ( 100% ) . in the supraclavicular lymph nodes ,
there were four cases ( 57.1% ) of metastatic adenocarcinoma , two cases ( 28.6% ) of metastatic squamous cell carcinoma and one case ( 14.3% ) of metastatic ductal carcinoma breast .
the inguinal group of lymph nodes formed an important metastatic site from the male external genitalia and ovaries .
the predominant cytological diagnosis was adenocarcinoma in three cases ( 50% ) , followed by two cases ( 33.3% ) of metastatic malignant melanoma , with smear showing pleomorphic tumor cells with enlarged eccentric nuclei and eosinophillic granular cytoplasm , and a single case ( 16.7% ) of undifferentiated carcinoma .
in the bone , nine cases ( 52.9% ) were diagnosed as metastatic adenocarcinomas on fnab .
almost all cases with skeletal metastases showed metastatic foci in the vertebral column and the upper end of the femur while there was a single case of metastatic foci at the upper end of the humerus in a case of breast carcinoma . in the liver , 11 cases ( 84.6% ) were found to be of metastatic adenocarcinoma on cytological examination , with a majority of the primary lesions located in the gall bladder and gastrointestinal tract .
the skin showed three cases ( 21.4% ) of metastatic adenocarcinoma , all of which had primaries in the lung .
a single case of squamous cell carcinoma lung with metastasis to the skin was also seen .
most of the metastatic tumors were located on the anterior chest wall , eight cases ( 57.1% ) , followed by nodules on the scalp , five cases ( 35.7% ) , and a single case was located on the skin around the elbow .
histopathological examination of the suspected primary site was performed in 16 cases and also in the same number of cases where cytology of the metastatic site was inconclusive , either due to hemorrhagic and necrotic background or poor representative cellularity .
mesenteric lymph node was observed as a metastatic site in three cases with primary being adenocarcinoma intestine .
there were five cases of metastatic bone tumors and two cases of metastatic papillary adenocarcinoma of liver with primary colorectal tumor .
omentum was observed as a site of metastasis in four cases ( 25% ) , with primary site being the ovaries in all the cases .
two cases were observed to be ovarian cystadenocarcinoma with peritoneal implants and one case each of granulosa cell tumor and yolk sac tumor of the ovary with peritoneal implants .
an isolated case of endometrial choriocarcinoma with metastasis to the brain was noted , where contrast - enhanced computed tomography of the head showed multiple nodular and ring - enhancing lesions in the both cerebral hemisphere with surrounding edema [ figure 2 ] along with a case of adenosquamous carcinoma of the cervix with extension into the uterine cavity .
all the primary tumor sites with their respective metastatic sites are depicted in table 2 .
contrast - enhanced computed tomography ( head ) showing multiple nodular and ring - enhancing lesions in both cerebral hemisphere with surrounding edema secondary to choriocarcinoma
patients with a suspected metastatic lesion were included in the present study and evaluated by means of a careful history , physical examination , pathological review and axillary radiological investigations to ascertain the primary site .
the majority of the lesions , i.e. , 90.6% , were diagnosed by fine needle aspiration biopsy , a modality of immense help as it is rapid , safe and cost - effective in determining the nature of a variety of metastatic lesions .
our study revealed a slight male predominance , with more than 85% cases between 40 and 60 years and above , which corresponds to the series reported by didolkar et al .
the youngest patient was a 3-year old boy with a subcutaneous scalp swelling , who was found to be harbouring a metastatic wilm 's tumor .
on analysis of the frequency of metastatic tumors at various metastatic sites , we observed that lymph nodes were the most common site ( 67.3% ) , an observation in concordance to findings of 76.8% by sinha et al .
snee and vyramuthu observed the bone to be the most frequent site of metastasis ( 55.0% ) , followed by lymph nodes in 28% of the cases .
the second most frequent site in our study was the bone ( 9.9% ) , followed by liver ( 8.8% ) .
similarly , sinha et al . , also observed bone to be the second most frequent metastatic site ( 9.6% ) , followed by the liver ( 7.7% ) .
the distribution of primary tumors at various metastatic sites in our study showed the pharyngolarynx and the oral cavity to be harboring the maximum number of cases , ( 32.2% ) .
sinha et al . , also observed maximum number of primaries in the pharyngolarynx and the oral cavity .
however , our findings were in variance to those of didolkar et al . , who reported the lung ( 40% ) to be the most common primary site followed by pancreas and stomach ( 6.5% each ) . in our study on analysis of cytohistological diagnosis of metastatic lesions
, we observed squamous cell carcinoma to be the predominant type of tumor ( 38.2% ) , followed by adenocarcinoma in 26.8% of the cases .
but , our observations differed from those made by didolkar et al . , who reported metastatic adenocarcinoma as the most common type of tumor , in 61% of the cases .
this discrepancy could be because these authors restricted their study strictly to metastatic lesions with unknown or occult primary and excluded all cases with a known primary detected through history , clinical examination and radiological work up .
cervical nodes were the most common metastatic site , with squamous cell carcinoma being the most common cytomorphological type in our study , a finding similar to that reported by sinha et al . , and jacobson et al .
thirty - one cases had metastatic lesions in the axillary group of lymph nodes , all of which had a primary in the breast .
similar findings were also observed by sinha et al . , and copeland et al .
carter et al . , asserted that tumor size and extent of axillary lymph node involvement were found to act as important independent but additive prognostic indicators in cases of breast cancer .
metastatic lesion in the supraclavicular lymph nodes was observed in seven cases , with lung being the most common primary site , three cases ( 42.9% ) followed by two cases ( 28.6% ) of metastasis from the colorectum and a single case each from the breast and unknown primary .
, who observed the lung to be an important primary site for metastasis in the right supraclavicular lymph nodes .
three cases ( 50% ) had a primary in the male genital tract and two cases ( 33.3% ) were metastatic malignant melanoma , while there was a single case of undifferentiated carcinoma .
copeland et al . , also observed malignant lesions arising in the lower extremity , perineum and , male and female genital tracts to be important primary sites for inguinal lymph node metastases .
we observed prostate in males ( 23.5% ) , and breast in females ( 17.6% ) ; to be the most common primary sites with skeletal metastasis .
our findings are concordant with the observations of hage et al . , who observed primary tumors in the prostate and breast in 31.2% and 30.6% cases , respectively .
katagiri et al . , observed the lung to be the most frequent primary site ( 35.5% ) , followed by prostate ( 17.2% ) and breast ( 7.8% ) .
buckwalter , in his autopsy studies , has revealed that 50 - 70% of the prostatic cancer patients developed skeletal metastasis during the course of their disease .
the most common sites of primary tumors with hepatic metastases in the present study were gall bladder and colorectum in 33.3% and 26.7% of the cases respectively , with 86.7% of the metastatic lesions being adenocarcinoma .
our study revealed anterior chest wall ( 57.1% ) and scalp ( 35.7% ) to be the most common site of metastases to the skin .
similar findings have been reported by brownstein and hellwig , who observed the anterior chest wall and head and neck to be the most common sites for metastasis in the skin .
saikia et al . , have stated that the skin on the entire body , and especially , that on the scalp should be examined carefully when a primary internal malignancy or recurrence of one is suspected .
the most critical aspect of the evaluation of metastatic cases is the accurate pathologic assessment of the malignant tissues in conjunction with pertinent clinical data .
such close collaboration between the clinician and the pathologist may maximize the diagnostic potential in treatable primary tumors .
aims : to ascertain the cytological diagnosis of metastatic lesions with special reference to the clinicopathological analysis of the primary site in cases of epithelial and non - epithelial tumors.materials and methods : one hundred seventy - one suspected metastatic lesions were aspirated with a 22 - 23 g needle and the smears were fixed and stained . 
 the cases in which the primary site was not evident at the time of initial presentation were subsequently subjected to thorough physical examination followed by radiological investigations for the search of the primary site . 
 histopathological examination was performed in 16 cases with inconclusive cytological impression.observations:of the total cases of metastatic lesions , 155 cases ( 90.6% ) were diagnosed by fine needle aspiration biopsy and 16 cases ( 9.4% ) by histopathology . 
 the majority of the cases , 81 ( 47.4% ) , were observed in the fifth decade of life , followed by 76 cases ( 44.4% ) in the sixth decade and 11 cases ( 6.4% ) in the seventh decade of life . 
 lymph nodes were the most frequent site of metastasis in 115 cases ( 67.3% ) , with the majority in the cervical group . 
 the oropharynx , including the oral cavity and pharyngolarynx , was observed to be the most common primary site , 55 cases ( 32.2%).conclusion : the most critical aspect of the evaluation of metastatic cases is the accurate pathologic assessment of the malignant tissues in conjunction with pertinent clinical data . 
 such close collaboration between the clinician and the pathologist may maximize the diagnostic potential in treatable primary tumors .