A 69-year-old Caucasian male who is regularly followed for idiopathic hyper-eosinophilic syndrome presents for a routine checkup. Clinical examination identifies a hard, irregular, left, inguinal lymph node measuring 1.5 × 1.5 cm.
Although he has no symptoms and his medical history is uneventful, his medical comorbidities include ischemic heart disease, diabetes, high blood pressure, and dyslipidemia. The patient is also a smoker.
A positron emission tomography (PET) scan confirms the presence of an isolated, hyper-metabolic, inguinal adenopathy of 1.9 cm. A subsequent percutaneous ultrasound-guided core biopsy reveals a poorly differentiated neuroendocrine carcinoma which has metastasized.
Immunohistochemical staining of the biopsy finds the tumor cells are negative for cytokeratin 7 (CK-7), p40, thyroid transcription factor 1 (TTF-1), prostate-specific antigen (PSA), and chromogranin-A. They are weakly positive for cytokeratin 20 (CK-20), moderately positive for synaptophysin, and strongly positive for CD56. The Ki-67 is elevated at 95%.
Biochemical test results are mostly in the normal range. However, chromogranin-A is persistently elevated at 1,400 ng/mL (normal value <101.9 ng/mL). A polypoid tumor lesion of the left bladder wall, 2.1 × 1.5 × 2.0 cm, is identified on ultrasound of the abdomen and pelvis.
Cystoscopy identifies a low-grade, papillary, noninfiltrating urothelial carcinoma, which is completely resected (pTa). Colonoscopy reveals four tubular adenomas with low-grade dysplasia – these are radically resected.
March 2017
An excisional, inguinal lymph node biopsy is scheduled. Clinical examination prior to the surgery finds that the lesion has completely regressed. This is confirmed by a PET scan that identifies a residual, swelling of the lymph node which is not hyper-metabolic. Histologically, the finding corresponds to a lymph node with a central sclero-hyalinosis and a normal cortex in the absence of any tumor infiltration.
Five months later
Clinical examination identifies another left, inguinal lymph node, later confirmed by a PET scan revealing a hyper-metabolic adenopathy of 1.2 cm (Figure).
Treatment and Outcome
Another excisional biopsy is performed. Histological examination finds a massive infiltration of poorly differentiated, small, neuroendocrine tumor cells with a scant cytoplasm and prominent mitotic figures. Tumor cells are positive for CD56, synaptophysin, and cytokeratin AE1/AE3, and negative for CK-7, CK-20, chromogranin- A, and CM2B4 (anti-polyomavirus). Based on these findings, clinicians diagnose the patient with Merkel cell carcinoma (MCC) metastasis.
Regional radiotherapy is performed (50 Gy in 25 fractions) after the patient refuses a proposed radical lymph node dissection.
Ten months later
A follow-up assessment finds the patient to be in good clinical condition and there is no recurrence of the tumor. His hyper-eosinophilic syndrome is stable. Interestingly, his serum levels of chromogranin-A are elevated, despite there being no evidence of a tumor on the PET scan.
Discussion
Authors of this note that their hyper-eosinophilic patient represents a rare case in presenting with an isolated, inguinal lymph node metastasis from a primary unknown Merkel cell carcinoma that regresses spontaneously following an ultrasound-guided core needle biopsy.
is a rare, aggressive primary cutaneous neuroendocrine tumor that typically occurs in people in their 6th and 7th decade of life. Only 5% of reported cases have occurred in people below the age of 50. The incidence of MCC has tripled over the last 15 years.
Typically the tumor develops on the sun-exposed skin, with the majority occurring on the head and neck region (47%-50%) or the extremities (40%), followed by the trunk (5%-10%).
Prognosis for patients with Merkel cell carcinoma is generally poor, case authors note, with a 5-year overall survival of about 60%. Regional lymph nodes are already involved at diagnosis in 10%–45% of cases, a feature that is strongly predictive of prognosis. About 50% of patients have distant metastases, often to the lymph nodes, liver, bone, brain, lung, and skin.
Risk of MCC is increased in patients with chronic immunosuppression, such as those chronic T-cell dysfunctions such as solid organ transplantation, HIV infection, and chronic lymphocytic leukemia, case authors write.
The hypothetical viral etiology of MCC was validated in 2008, when a new human polyomavirus (Merkel cell polyomavirus: MCPyV) was found to be integrated into the genome of 80% of analyzed cases of human MCC. This has subsequently been confirmed by many studies, although its role in MCC prognosis is still controversial and not well established.
Despite the noted aggressiveness of MCC, complete spontaneous regression in the absence of any specific treatment has been reported in the literature. In some cases, tumor regression followed incisional biopsy, thus supporting the hypothetical role of surgery-induced inflammation in the regression, case authors note.
Complete spontaneous regression of MCC, first described in 1986, accounts for approximately 1.4% of all reported cases (15 out of 1100). Case authors point out that this is a much higher incidence when compared to all other cancers, which have an incidence rate of 1 out of 60,000 to 100,000.
Interestingly, MCC complete spontaneous regression typically has rapid onset of 1 to 5 months and is maintained with a few reported cases of recurrence, authors write. It is more often seen in women, and is usually associated with better disease-specific survival.
The reason for complete spontaneous regression pathogenesis remains undetermined, but it is thought to be related to T-cell-mediated immunity. Accumulation of chronic inflammatory cells, mainly T-cells and foamy macrophages, after tumor biopsy, have been observed in several histopathologic studies.
Furthermore, authors note, T-cell related cytokines, such as interferons, can promote effective immune responses against neuroendocrine tumors. Interestingly, in another , a rare, complete spontaneous remission of metastatic MCC examines the potential role of the patient's use of several alternative therapies.
While diagnostic biopsy may have a role in stimulating a T-cell mediated immune response, data concerning the prognostic value of intra-tumoral and/or peri-tumoral CD8+ lymphocyte infiltration remain controversial.
Conclusions
This case appears to be unique in reporting complete spontaneous regression of MCC in a patient with idiopathic hyper-eosinophilic syndrome and without a primary tumor, which they suggest occurred following a percutaneous, ultrasound-guided core needle biopsy, with a relapse in a nearby lymph node 5 months later.
References:
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Disclosures
Authors had no disclosures.
Primary Source
Am J Case Reports
Longo R, et al "A Spontaneous Regression of an Isolated Lymph Node Metastasis from a Primary Unknown Merkel Cell Carcinoma in a Patient with an Idiopathic Hyper-Eosinophilic Syndrome" Am J Case Rep 2018; 19: 1437-1440