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 Table of Contents  
CASE REPORT
Year : 2018  |  Volume : 6  |  Issue : 1  |  Page : 122-125

Cytological, histopathological and immunohistochemical features of merkel cell carcinoma- A case report


Department of Pathology, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India

Date of Web Publication11-Jun-2018

Correspondence Address:
Dr. Pooja Chauhan
H. No. 51, Housing Board Colony, Sanyard, P. O. Talyahar Distt., Mandi - 175 001, Himachal Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/amhs.amhs_27_18

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  Abstract 


Merkel cell carcinoma (MCC) is a rare, potentially aggressive primary cutaneous neuroendocrine carcinoma. MCC commonly occurs on sun-exposed skin in fair-skinned elderly individuals. It usually presents as a banal-appearing lesion, and the diagnosis is rarely suspected at the time of biopsy. We describe the cytomorphologic, histopathological, and immunohistochemical characteristics of MCC in a 76-year-old male patient presenting with rapidly evolving large red raised lesion over cheek for 1 month. Cytohistopathological evaluation suggested MCC. Immunohistochemistry revealed that the tumor cells were negative for leukocyte common antigen, S-100 protein, HMB45, and cytokeratin 20 and positive for neuron specific enolase. Because of the documented aggressiveness and rising incidence, early diagnosis of this rare tumor is necessary for the management of MCC.

Keywords: CK 20 negative, cutaneous neuroendocrine tumor, Merkel cell carcinoma


How to cite this article:
Chauhan P, Gupta N, Mardi K, Sharma SK, Negi A. Cytological, histopathological and immunohistochemical features of merkel cell carcinoma- A case report. Arch Med Health Sci 2018;6:122-5

How to cite this URL:
Chauhan P, Gupta N, Mardi K, Sharma SK, Negi A. Cytological, histopathological and immunohistochemical features of merkel cell carcinoma- A case report. Arch Med Health Sci [serial online] 2018 [cited 2018 Dec 9];6:122-5. Available from: http://www.amhsjournal.org/text.asp?2018/6/1/122/234097




  Introduction Top


This is a rare tumor of the elderly presenting mainly in Caucasians (0.23 annual age adjusted incidence per 100,000) with a high concentration of primary tumors on sun-exposed sites.[1]

Merkel cell carcinoma (MCC) has a nonspecific clinical presentation although rapid growth of a firm, red to violaceous, nontender papule, or nodule is often noted. The majority of patients present with clinically localized disease. However, the disease can rapidly spread to regional and distant sites. Diagnosis is made through biopsy, almost invariably with the aid of immunohistochemistry (IHC), classically demonstrating a perinuclear dot pattern of cytokeratin-20 staining.[2] We describe the cytological, histological, and IHC features of MCC.


  Case Report Top


A 76-year-old male presented with a red raised lesion over the left cheek with involvement of the same side eyelid, rapidly progressing to the present size of 6 cm × 5 cm × 6 cm over 1 month. The swelling was covered over by black adherent crust. Surrounding skin was erythematous and edematous [Figure 1]. There was no associated itching or pain and bled on trivial trauma. There were no systemic complaints. Contrast-enhanced computerized tomography paranasal sinus and nose showed heterogeneously enhancing mass in subcutaneous plane of the left cheek, maxillary prominence, nasofacial groove with wide spread extension posteriorly to maxillary sinus, bony erosion, and cervical lymphadenopathy. Clinically, possibility of keratoacanthoma, squamous cell carcinoma, and basal cell carcinoma (BCC) were suggested.
Figure 1: Ulcerated lesion over the left cheek of size of 6 cm × 5 cm × 6 cm (pretreatment)

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Fine needle aspiration (FNA) revealed cellular smears with tumor cells lying singly, in trabeculae and in acini showing marked cellular and nuclear pleomorphism with slightly irregular and eccentrically placed nuclei, reticulogranular chromatin, variably conspicuous nucleoli and moderate amount of fragile basophilic cytoplasm [Figure 2] and [Figure 3]. Frequent multinucleate tumor giant cells, increased apoptosis, atypical mitosis, and emperipolesis were also seen.
Figure 2: Fine needle aspiration cytology smear shows pleomorphic tumor cells in a hemorrhagic background (Giemsa stain, ×100)

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Figure 3: Fine needle aspiration cytology smear revealing pleomorphic tumor cells with reticulogranular chromatin, arranged in clusters, trabeculae, and acini (Giemsa stain, ×400)

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Histopathological examination of biopsy revealed tumor cells separated by grenz zone from overlying epithelium and arranged in sheets, trabeculae, and acini. Tumor cells had pleomorphic round to irregular nuclei, vesicular chromatin, conspicuous 1–3 macronucleoli, and moderate amount of eosinophilic to vacuolated cytoplasm. Frequent multinucleate tumor giant cells, extensive area of necrosis, increased apoptosis, brisk mitosis, and emperipolesis were also seen [Figure 4], [Figure 5], [Figure 6]. Diagnosis of MCC was given both on cytology and histopathology. On IHC, tumor was CD 45, HMB 45, CK 20 negative, and neuron-specific enolase positive [Figure 7]. The patient underwent radiotherapy as extensive spread of tumor had rendered surgery impossible and showed dramatic improvement [Figure 8].
Figure 4: Extensive areas of necrosis (H and E, ×10)

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Figure 5: Tumor cells separated from epidermis by a grenz zone (H and E, ×10)

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Figure 6: Tumor cells had pleomorphic round to irregular nuclei, conspicuous 1–3 macronucleoli, moderate amount of eosinophilic to vacuolated cytoplasm. Atypical mitotic figure is also seen (H and E, ×100)

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Figure 7: Tumor cells neuron-specific enolase positive and CK20, HMB45, CD 45 negative (IHC, ×10)

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Figure 8: Posttreatment

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  Discussion Top


MCC often presents as a rapidly growing, asymptomatic, reddish-blue dermal papule or nodule that develops over the course of weeks to months; the primary lesion of MCC is distinguished by its absence of distinctive clinical characteristics. Rarely suspected at the time of biopsy, the clinical differential diagnosis includes more common lesions such as BCC, epidermoid cyst, or even amelanotic melanoma.[3]

It primarily affects the sun-exposed areas of the skin, with approximately 50% of all tumors occurring in the face and neck, 40% appear on the extremities, and 10% on the trunk and genitals. Rare occurrences in sun-protected areas have been described. The tumor spreads frequently; common secondary sites include the skin (28%), lymph nodes (27%), liver (13%), lung (10%), bones (10%), and brain (6%).[4]

Many primary and metastatic tumors may resemble MCC. FNA cytology of MCC is usually cellular and composed of small- to medium-sized cells in a predominantly single-cell pattern. The nuclei are uniform, round to oval, with delicate nuclear membranes and finely granular chromatin pattern. The cytoplasm is scanty. Rosette formation is very rare. Frequent mitotic figures and individual cell necrosis are frequently noted.[5]

On histopathology, MCC arises in the dermis and frequently extends into the subcutaneous fat. The tumor is composed of small blue cells with hyperchromatic nuclei and minimal cytoplasm. Mitoses are frequently abundant, and apoptosis is often widespread. Lymphovascular invasion is an almost invariable feature.[4]

The major differential diagnosis includes metastatic oat cell carcinoma, metastatic carcinoids, malignant lymphomas, and occasionally, other tumors such as melanomas composed of small cancer cells, and very remotely, BCC that may be composed of cells of similar sizes. Except for BCC that forms cohesive clusters of cells, all other tumors show dispersed cancer cells.[6]

Immunohistochemical demonstration of neuron-specific enolase, intense staining for keratins (CK7 and CK20), and absence of S100 protein, leukocyte common antigen, and HMB45 are enough to confirm the diagnosis. Cytokeratin 20 presents dot-like and crescent patterns. Occasional cases of MCC are negative for CK20.[7] It has been reported that CK20 is expressed in 87% of MCCs [8] as also seen in our case. Thyroid transcription factor-1 may help with the differential diagnosis from metastatic small cell carcinoma because no reactivity has been shown in MCC.[7]

Our case underlines that caution should be taken in excluding the diagnosis of MCC only on the basis of the absence of immunoreactivity for CK20, favoring the wrong diagnosis of less aggressive skin tumors and panel of antibodies be used in differential diagnosis in morphologically similar skin tumor.

The National Comprehensive Cancer Network 2010 guidelines for the management of MCC recommended excision of the primary tumor whenever possible. Complete local lymph nodal dissection is recommended for sentinel lymph-node biopsy (SLNB) positive or palpable-nodal disease. Adjuvant radiation therapy to the excised tumor bed and draining lymph node basin regardless of SLNB results is suggested as a means of minimizing regional recurrence. Radiation alone is also listed as an acceptable alternative to surgery when excision is not feasible or is refused by the patient. Chemotherapy with or without surgery and radiation therapy is reserved for Stage IV disease and is generally palliative.[9]


  Conclusion Top


MCC is an aggressive cutaneous malignancy whose clinical diagnosis is seldom made at the time of clinical presentation. The incidence of MCC is on the rise, and increasing awareness along with advances in immunohistopathologic staining has greatly aided in diagnosis. The IHC profile of our case underlines that caution should be taken in excluding the diagnosis of MCC only on the basis of the absence of immunoreactivity for CK20 and that a panel of antibody should be used in differential diagnosis of morphologically similar skin tumors.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Calonje E. Tumors of the skin appendages. In: Burns T, Breathnach S, Cox N, Griffiths C, editors. Rook's Textbook of Dermatology. 8th ed., Vol. 53. Edinburgh: Wiley Blackwell; 2010. p. 42-3.  Back to cited text no. 1
    
2.
Compton CC, Bryd DR, Aguilar TG, Kurtzman SH, Olawaiye A, Washington MK. Merkel Cell Carcinoma: AJCC Cancer Staging Atlas. Springer New York: USA; 2012. p. 371-83.  Back to cited text no. 2
    
3.
Wang TS, Byrne PJ, Jacobs LK, Taube JM. Merkel cell carcinoma: Update and review. Semin Cutan Med Surg 2011;30:48-56.  Back to cited text no. 3
[PUBMED]    
4.
Goessling W, McKee PH, Mayer RJ. Merkel cell carcinoma. J Clin Oncol 2002;20:588-98.  Back to cited text no. 4
[PUBMED]    
5.
Lin O, Zakowski M. Cytology of soft tissue, bone, and skin. In: Bibbo M, Wilbur D, editors. Comprehensive Cytopathology. 3rd ed. Philadelphia: Saunders, Elsevier; 2008. p. 506.  Back to cited text no. 5
    
6.
Koss LG, Melamed MR. Skin. In: Koss's Diagnostic Cytology and Its Histopathologic Bases. 5th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2006. p. 1297.  Back to cited text no. 6
    
7.
Divani S, Vardouli A, Reppas S, Alexopoulou V, Skoulakis C, Valagiannis D. Neuroendocrine (merkel cell) carcinoma of the auricle. Arch Oncol 2004;12:208-9.  Back to cited text no. 7
    
8.
Bobos M, Hytiroglou P, Kostopoulos I, Karkavelas G, Papadimitriou CS. Immunohistochemical distinction between merkel cell carcinoma and small cell carcinoma of the lung. Am J Dermatopathol 2006;28:99-104.  Back to cited text no. 8
[PUBMED]    
9.
Nasseri E. Merkel cell carcinoma. Can Fam Physician 2012;58:967-9.  Back to cited text no. 9
[PUBMED]    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]



 

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