merkel cell carcinoma ( mcc ) also known as neuroendocrine carcinoma of skin is an uncommon tumor of the skin that accounts for a small fraction of cutaneous malignancies . however , the age - adapted incidence appears to have tripled between 1986 to 2001 , with a statistically significant annual increase of 8% . it presents as a rapidly growing skin nodule usually on the sun - exposed parts of the body , predominantly in males , with a mean age of 70 years at the time of diagnosis . it is an aggressive tumor and shows a tendency for local recurrence , lymph node involvement , and distant metastasis . a 70-year - old woman , a known case of senile dementia presented to the surgery outpatient department with lump on her abdominal skin since six months and discharge through the lump since two weeks . an infraumbilical midline scar elicited a history of hysterectomy 30 years back for dysfunctional uterine bleeding . there was no history of immunosuppressive treatment , and enzyme - linked immunosorbent assay for hiv was negative . a mass was noted on the abdominal wall below and to the right side of umbilicus . it was 8  8 cm in size , soft , nontender , with surface ulceration and bluish in color . she was admitted to the surgical ward and a fine - needle aspiration biopsy ( fnab ) of the abdominal lump was done . the fnab showed cellular smears consisting of small round cells arranged in groups , clusters , as well as singly scattered [ figure 1 ] . a differential diagnosis of small cell carcinoma , lymphoma , and neuroendocrine carcinoma was offered . a wide local excision of the abdominal lump was done under general anesthesia after routine hematological and biochemical investigations . intraoperatively , the lump was mainly subcutaneous extending up to and involving the rectus sheath for an area of approximately 2 cm diameter . gross examination of the surgical specimen received in pathology department consisted of a skin covered bluish , firm mass measuring 8  7 5 cm . an ulceroproliferative , irregular growth was seen fungating through skin measuring 4.5  4.5  3 cm . microscopic examination showed a poorly circumscribed tumor in the reticular dermis of skin [ figure 3a ] infiltrating the subcutaneous tissue . the tumor cells were small having a large hyperchromatic nucleus with a small rim of cytoplasm . the cells were arranged in nests , chords , and trabeculae as well as in sheets . on immunohistochemistry cytokeratin 20 ( ck20 , dako clone ks-20.8 ) , synaptophysin ( syn , novocastra clone 27g12 ) , and neuron - specific enolase ( nse , novocastra clone 5e2 ) were positive and showed cytoplasmic positivity [ figure 4 ] . groups and clusters of small round cells having hyperchromatic nuclei gross specimen of the tumor showing an exophytic growth , infiltrating into the subcutaneous fat ( a ) the tumor in the reticular dermis of skin ( hematoxylin and eosin , 40 ) , ( b ) showing the small cells arranged in trabeculae showing salt and pepper chromatin ( hematoxylin and eosin , 400 ) ( a ) perinuclear dot - like immunoreactivity for ck20 ( b ) cytoplasmic immunoreactivity for neurone - specific enolase , ( c ) cytoplasmic immunoreactivity for synaptophysin ( 400 ) the first description of mcc can be traced to toker ( 1972 ) who called it trabecular carcinoma of the skin . tang and toker ( 1978 ) found dense core granules in the cytoplasm of the tumor cells by electron microscopy . however , some authors believe that mcc arises from pleuripotent stem cells of the skin . the name merkel cell carcinoma was proposed by de wolff - peeters in 1980 and is the most accepted term . in mammals , merkel cells ( mc ) are found in the basal layer of the skin and mucosa either as single cells or in clusters . they also function as neuroendocrine cells , secreting metenkephalin , vasoactive intestinal polypeptide , substance p , and calcitonin gene - related peptide to transmit or transduce chemical information . their morphology can be seen under electron microscopy whereby they are seen to have lobulated nuclei , a loose cytoskeletal network of intermediate filaments , dense core cytoplasmic granules , and spine - like microvilli protruding from the surface into invaginations in surrounding keratinocytes . a nation - wide incidence of mcc was extracted from the danish cancer registry by lyhne et al . incidence rates had increased 5.4 times over the period of 18 years . in surveillance , epidemiology and end results ( seer ) program data from 1986 to 2001 , the age - adjusted us annual incidence of mcc tripled from 0.15 to 0.44 per 1,00,000 , which is an increase of 8.08% per year . incidence is greater in whites than in blacks and slightly higher in males than in females . the increase in incidence may reflect an actual increase and/or more accurate diagnostic pathology tools , increased awareness of mcc , an aging population , increased sun exposure in susceptible population , and improved registry tools . mcc typically develops as a painless , nontender rapidly growing nodule or plaque , mostly located on sun - exposed areas of the body of an elderly person . the nodule is solitary , firm , flesh colored - to - reddish - blue , having a smooth shiny surface . the reported age range has been from 7 to 95 years and majority of patients are older than 65 years . the skin of head and neck is affected in 50% cases , extremities in 40% , and trunk and mucosa in 10% . the clinical differential diagnosis includes basal cell carcinoma , squamous cell carcinoma , pyogenic granuloma , keratoacanthoma , amelanotic melanoma , benign cyst , adenexal tumor , lymphoma , and metastatic carcinoma . ( 1 ) trabecular type with connective tissue separating interconnecting cellular trabeculae , ( 2 ) intermediate cell type , which is most common , consisting of solid nests with trabeculae at the periphery , and ( 3 ) small cell type consisting of sheets of small cells with a diffusely infiltrative pattern . the tumor cells are rounded , monomorphic , small to medium sized with scanty cytoplasm , round nuclei with inconspicuous nucleoli ( blue cells ) . the nuclei have finely granular chromatin and may show the typical salt and pepper appearance . other malignant neoplasms such as actinic keratosis , bowen disease , basal cell carcinoma , squamous cell carcinoma , and sweat gland tumors have been reported within or adjacent to lesions of mcc . ectopic anti diuretic hormone secretion by a neuroendocrine tumor with mcc phenotype was recently reported . the histologic differential diagnosis includes malignant melanoma , lymphoma , and cutaneous small cell epithelial tumors such as small cell squamous cell carcinoma , basal cell carcinoma , sweat gland carcinoma , and metastatic neuroendocrine carcinoma . the loosely arranged intermediate filaments are stained by low molecular weight cytokeratins ( ck ) 8 , 18 , 19 , and 20 . ck20 in particular has been shown to be a highly specific marker for mc in normal skin where it is a diffuse cytoplasmic stain . the dense core granules of mc show immunoreactivity for neuroendocrine markers chromogranin , synaptophysin , and neuron - specific enolase . in 1992 , it stains 80%90% of all mcc in a characteristic paranuclear dot - like pattern , which is due to clumping of intermediate filaments . neurofilament immunostains are also positive in a paranuclear dot - like pattern in up to 95% of mcc . mcc also frequently stain positive for neuroendocrine markers chromogranin , neuron - specific enolase , and synaptophysin . thyroid transcription factor-1 staining is useful to distinguish metastatic small cell carcinoma of lung from mcc . merkel cell polyoma virus ( mcpyv ) association : in 2008 , feng et al . studied mcc samples by digital transcriptome subtraction and detected a fusion transcript between a previously undescribed virus t antigen and a human receptor tyrosine phosphatase . further investigation led to identification and sequence analysis of the 5387 base pair genome of a previously unknown polyomavirus that they called merkel cell polyomavirus ( mcpyv ) . mcpyv sequences were detected in 8 out of 10 ( 80% ) mcc tumors but only 5 out of 59 ( 8% ) control tissues from various body sites and 4 out of 25 ( 16% ) control skin tissues . in 6 out of 8 mcpyv - positive mccs , viral dna was integrated within the tumor genome in a clonal pattern suggesting that viral infection and integration occurred before the clonal expansion of the tumor cells . since the publication of this study , additional studies have substantiated that approximately 80% of mcc contain mcpyv . reported that compared with mcpyv dna  negative cancers , mcpyv dna  positive cancers were more often located in a limb ( 40.7% vs 8.7% , p = 0.015 ) and less frequent in patients who had regional nodal metastases at diagnosis ( 6.6% vs 21.7% , p = 0.043 ) . patients with mcpyv dna  positive tumors had better overall survival than those with mcpyv dna  negative tumors ( 5-year survival : 45.0% vs 13.0% , respectively ; p < 0.001 ) . one recent study done to evaluate mcpyv seroprevalence and seroconversion among adult men at risk for hiv infection suggests that mcpyv infection is a highly prevalent infection among adults that is often asymptomatic . antibodies recognizing mcpyv large and small tumor - associated antigens are relatively specifically associated with mcc , do not effectively protect against disease progression , and may serve as a clinically useful indicator of disease status . it has been estimated that the risk of mcc increases 15-fold over the general population in immunosuppressed patients ( chronic lymphoid leukemia , hiv infection , immunosuppressive treatment ) . spontaneous regression has been reported in mcc , and the estimated rate of regression is 1.4% . eaton myasthenic syndrome , brainstem encephalitis , and others have been observed in mcc . in 2010 , american joint committee on cancer released its first consensus staging system for mcc and is reported in the literature . the present case was pt3n1bmx ( over 5 cm maximum tumor dimension with macrometastasis in regional lymph nodes ) , stage iiib . evaluated retrospectively the following histologic features with regard to prognosis : tumor thickness , microanatomic compartment involved by the tumor ( dermis , subcutis , deeper ) , lymphovascular invasion , tumor - infiltrating lymphocytes , tumor necrosis , ulceration , and solar elastosis . they found that tumor architecture ( nodular or infiltrative ) , tumor thickness , and lymphovascular invasion are independent predictors for survival along with tumor stage in patients of mcc . they are tumor excision with 1 cm margins for tumors < 2 cm in size and 2 cm margins for those > 2 cm in size . sentinel lymph node biopsy ( sln ) is currently recommended for all untreated , clinically node - negative primary mcc at the time of wide local excision . sln biopsy is needed for proper staging of tumor and should be examined both by hematoxylin and eosin ( h and e ) stain and immunohistochemistry . if sln is positive complete lymph node dissection followed by radiotherapy is recommended . in case sln is positive on immunohistochemistry only , then radiotherapy without lymph node dissection may be considered . it is used as primary therapy only in inoperable cases and when the patient refuses surgery . in the present case , wide local excision with 2 the histologic differential diagnosis includes malignant melanoma , lymphoma , and cutaneous small cell epithelial tumors such as small cell squamous cell carcinoma , basal cell carcinoma , sweat gland carcinoma , and metastatic neuroendocrine carcinoma . the loosely arranged intermediate filaments are stained by low molecular weight cytokeratins ( ck ) 8 , 18 , 19 , and 20 . ck20 in particular has been shown to be a highly specific marker for mc in normal skin where it is a diffuse cytoplasmic stain . the dense core granules of mc show immunoreactivity for neuroendocrine markers chromogranin , synaptophysin , and neuron - specific enolase . in 1992 , dr . it stains 80%90% of all mcc in a characteristic paranuclear dot - like pattern , which is due to clumping of intermediate filaments . neurofilament immunostains are also positive in a paranuclear dot - like pattern in up to 95% of mcc . mcc also frequently stain positive for neuroendocrine markers chromogranin , neuron - specific enolase , and synaptophysin . thyroid transcription factor-1 staining is useful to distinguish metastatic small cell carcinoma of lung from mcc . merkel cell polyoma virus ( mcpyv ) association : in 2008 , feng et al . studied mcc samples by digital transcriptome subtraction and detected a fusion transcript between a previously undescribed virus t antigen and a human receptor tyrosine phosphatase . further investigation led to identification and sequence analysis of the 5387 base pair genome of a previously unknown polyomavirus that they called merkel cell polyomavirus ( mcpyv ) . mcpyv sequences were detected in 8 out of 10 ( 80% ) mcc tumors but only 5 out of 59 ( 8% ) control tissues from various body sites and 4 out of 25 ( 16% ) control skin tissues . in 6 out of 8 mcpyv - positive mccs , viral dna was integrated within the tumor genome in a clonal pattern suggesting that viral infection and integration occurred before the clonal expansion of the tumor cells . this suggested that mcpyv may be a contributing factor in pathogenesis of mcc . since the publication of this study , additional studies have substantiated that approximately 80% of mcc contain mcpyv . reported that compared with mcpyv dna  negative cancers , mcpyv dna  positive cancers were more often located in a limb ( 40.7% vs 8.7% , p = 0.015 ) and less frequent in patients who had regional nodal metastases at diagnosis ( 6.6% vs 21.7% , p = 0.043 ) . patients with mcpyv dna  positive tumors had better overall survival than those with mcpyv dna  negative tumors ( 5-year survival : 45.0% vs 13.0% , respectively ; p < 0.001 ) . one recent study done to evaluate mcpyv seroprevalence and seroconversion among adult men at risk for hiv infection suggests that mcpyv infection is a highly prevalent infection among adults that is often asymptomatic . antibodies recognizing mcpyv large and small tumor - associated antigens are relatively specifically associated with mcc , do not effectively protect against disease progression , and may serve as a clinically useful indicator of disease status . it has been estimated that the risk of mcc increases 15-fold over the general population in immunosuppressed patients ( chronic lymphoid leukemia , hiv infection , immunosuppressive treatment ) . spontaneous regression has been reported in mcc , and the estimated rate of regression is 1.4% . eaton myasthenic syndrome , brainstem encephalitis , and others have been observed in mcc . in 2010 , american joint committee on cancer released its first consensus staging system for mcc and is reported in the literature . the present case was pt3n1bmx ( over 5 cm maximum tumor dimension with macrometastasis in regional lymph nodes ) , stage iiib . evaluated retrospectively the following histologic features with regard to prognosis : tumor thickness , microanatomic compartment involved by the tumor ( dermis , subcutis , deeper ) , lymphovascular invasion , tumor - infiltrating lymphocytes , tumor necrosis , ulceration , and solar elastosis . they found that tumor architecture ( nodular or infiltrative ) , tumor thickness , and lymphovascular invasion are independent predictors for survival along with tumor stage in patients of mcc . they are tumor excision with 1 cm margins for tumors < 2 cm in size and 2 cm margins for those > 2 cm in size . sentinel lymph node biopsy ( sln ) is currently recommended for all untreated , clinically node - negative primary mcc at the time of wide local excision . sln biopsy is needed for proper staging of tumor and should be examined both by hematoxylin and eosin ( h and e ) stain and immunohistochemistry . if sln is positive complete lymph node dissection followed by radiotherapy is recommended . in case sln is positive on immunohistochemistry only , then radiotherapy without lymph node dissection may be considered . it is used as primary therapy only in inoperable cases and when the patient refuses surgery . in the present case , wide local excision with 2 cm margin along with regional lymph node dissection was done .
merkel cell carcinoma also known as neuroendocrine carcinoma of the skin is a very rare skin tumor . 
 it commonly presents in the old age and the common sites are head , neck and extremities . 
 the diagnosis requires histopathological examination with immunohistochemical correlation . 
 we report a case of merkel cell carcinoma stage iiib with bilateral inguinal lymphadenopathy that on fnab showed metastatic deposits of the tumor .