Case of the Fortnight #1

Clinical history:

68-year-old male patient with rapidly growing swelling of 4 months duration. On the dorsal aspect of the forearm. O/e fairly well-circumscribed flesh-colored nodule., 2 x 1.8 cm. No history of other tumors in the body.

CASE OF THE FORTNIGHT Dr Gowripriya Consultant pathologist Dr Rela institute and medical center

MERKEL CELL CARCINOMA

• 68 YEAR OLD MALE PATIENT WITH RAPIDLY GROWING SWELLING OF 4 MONTHS DURATION.
• ON THE DORSAL ASPECT OF FOREARM.
• O/E FAIRLY WELL CIRCUMSCRIBED FLESH COLOURED NODULE., 2 X 1.8 CM.
• NO HISTORY OF OTHER TUMOURS IN THE BODY.

Fig 1: A nodular small round blue cell tumour centred in the dermis

Fig 2: Tumour cells arranged as sheets, nests and trabeculae, occasional pseudorosettes

Fig 3: Tumour cells with scant cytoplasm, molded nuclei with stippled chromatin

Fig 4: A rare instance of epidermotropism of tumour cells

Fig 5: Diffuse positivity with Synaptophysin

Fig 6: Characteristic paranuclear dot like positivity with CK 20 (some cases may show cytoplasmic positivity)

LEARNING POINTS:

• 1)A rare, aggressive, primary cutaneous neuroendocrine carcinoma.
• 2)Elderly males, sun exposed skin of head and neck/ extremities/ trunk
• 3)Immunosuppression and advanced age are risk factors.v
• 4)Cell of origin- unknown, possible precursors include Pro-B/ Pre-B lymphocytes, fibroblasts, dermal mesenchymal stem cells and epithelial cells.
• 5) Clinically, rapidly growing violaceous/ flesh coloured nodules.
• 6)Microscopy: Small blue round cell tumour in the dermis and/ or subcutis.
• • Cells with high nuclear: cytoplasmic ratio, salt and pepper chromatin.
  • Sheets/ nests/ occasional trabeculae/ pseudo-rosettes
  • Mitoses/ apoptosis/ necrosis.
  • Squamous differentiation maybe seen.
• 7)Immunohistochemistry:
• • Neuroendocrine markers
  • CK 20- paranuclear dot- like positivity
  • Neurofilament
  • SAT B2
  • Often , Merkel Cell Polyoma Virus (see below)
• 8)TWO MAJOR SUBSETS BASED ON VIRAL STATUS:

Feature	MCPyV-positive	MCPyV-negative (UV exposure related)
Incidence	More common	Less common
Morphology	Pure	Pure/ combined
Prognosis	Better	Worse
Tumor infiltrating lymphocytes	Brisk	Few
IHC	Rb pos (+++) P53 pos (+) P63 pos (+)	Rb pos (+) P53 pos (+++) P63 pos (+++)
Genetics	Tumour mutational burden	Tumour mutational burden
	low No Recurrent RB1/ P53 mutations No UV mutation signature	high Recurrent RB1/ P53 mutations UV mutation signature

• 9)Treatment: Excision, lymph node resections, Immune-checkpoint-inhibitors.
• 10)Data for inclusion in pathology reports:
• • Maximum dimension of tumor (gross or microscopic)
  • Tumor confined to dermis/subcutis: yes/no
  • Involvement of underlying muscle, fascia, bone or cartilage: yes/no
  • Lymphovascular involvement: yes/no
  • Distance from surgical margin
  • Local microscopic “satellite” deposits of tumor: yes/no
  • Distance between main tumor and deep surgical margin
  • Morphology (pure neuroendocrine or combined): pure or combined
  • Merkel cell polyomavirus status: positive or negative
  • Immunohistchemical profile
  • P63 expression: positive or negative

REFERENCES:

1)Noreen M. Walsh, Lorenzo Cerroni; Merkel cell carcinoma: a review, Journal of cutaneous pathology https://doi.org/10.1111/cup.13910

2)WHO classifcation of skin tumours, 4th ed.