Primary cutaneous neuroendocrine tumor with axillary lymph node metastasis: A clinical masqueradeP Manimaran, R Shah, P Trivedi, S Mehta
Department of Oncopathology, Gujarat Cancer Research Institute, Ahmedabad, Gujarat, India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/jpgm.jpgm_254_22
Source of Support: None, Conflict of Interest: None
A 63-year-old man presented with swelling in the presternal and right axillary region for 4 months. Initial biopsy from presternal mass showed only scant tissue thus inadequate for definite opinion but biopsy from right axillary lymph node showed a metastatic neuroendocrine tumor (NET). Therefore, a repeat biopsy from the presternal mass with radiological workup was advised to search for primary. Meanwhile, the patient was started on a chemotherapeutic regimen with tamoxifen, carboplatin, and etoposide but he was not responding to chemotherapy. Fine needle aspiration cytology (FNAC) of the thyroid showed benign follicular nodule but computed tomography (CT) scan showed multiple hypodense lesions in the left lobe of the thyroid with extracapsular and superior mediastinal extension. As positron emission tomography (PET) scan revealed heterogeneous uptake in presternal region, the upper pole of the left lobe of the thyroid, and remaining axillary nodal mass, clinically primary from thyroid was suspected and wide local excision of the presternal mass with left hemithyroidectomy, right axillary node dissection was done and sent for histopathological examination.
On gross examination, presternal mass revealed a 10 × 8 × 4 cm well-circumscribed gray-white to brown, firm tumor [Figure 1]a and thyroid showed multiple colloid-filled cystic spaces. Histology of presternal excised mass showed that the tumor was predominantly located in the dermis. Tumor cells were arranged in organoid, nested, trabecular, and solid patterns. The cells were medium to large in size showing moderate pleomorphism, having coarse and vesicular nuclear chromatin with prominent nucleoli. Focal areas of necrosis were noted. Mitosis was brisk [Figure 1]b, [Figure 1]c, [Figure 1]d. Morphologically it resembled the metastatic neuroendocrine tumor of the previous axillary lymph node biopsy. Thyroid showed adenomatoid hyperplasia. The right axillary lymph node showed metastatic NET. Immunohistochemical examination (IHC) showed strong positivity for epithelial membrane antigen (EMA), synaptophysin and chromogranin [Figure 2]a and [Figure 2]b, estrogen receptor (ER), progesterone receptor (PR), and GATA 3 binding protein. Ki67 proliferation index was 22%. All other markers like thyroid transcription factor-1 [Figure 2]c, paired-box gene 8 (PAX8), calcitonin, and caudal-related homeobox gene (CDX 2) were negative; thus primary from lung, thyroid, and gastrointestinal tract were excluded. Smooth muscle actin (SMA) and tumor protein 63 (P63) were negative in myoepithelial cells; thus endocrine mucin-producing sweat gland carcinoma was excluded [Figure 2]e and [Figure 2]f. Merkel cell carcinoma was ruled out by negative cytokeratin 20 (CK20) [Figure 2]d.
Correlating the morphology and IHC findings, two differential diagnoses were considered: 1) primary cutaneous NET and 2) primary breast NET because its location was in the presternal region. As management differs, it was essential to differentiate these tumors. Clinical and radiological findings favored primary cutaneous NET over breast primary. Therefore, the final diagnosis was given as primary cutaneous neuroendocrine tumor-grade 3 with axillary nodal metastasis.
Primary cutaneous neuroendocrine tumor is a rare slow-growing neoplasm with predilection for the scalp and anterior chest wall. Usually, it presents as an asymptomatic nodule hence mere surgical excision is curative. Among 15 cases described in the literature, only one case showed local recurrence, four cases showed regional lymph node metastasis,,,, and two cases showed distant metastasis., The present case showed axillary nodal metastasis with absent distant metastasis.
Morphologically, primary cutaneous NET is indistinguishable from metastasis from NET of visceral organs. Cutaneous metastasis is relatively uncommon, multifocal with poor prognosis. As surgical excision with adjuvant chemotherapy is the treatment modality, accurate diagnosis is needed.
Merkel cell carcinoma (MCC) is a high-grade neuroendocrine carcinoma showing a similar histological pattern but with numerous mitosis and apoptotic bodies. Immunohistochemically, it will show a dot like paranuclear CK20 positivity. As it is an aggressive disease, surgery and adjuvant radiotherapy are needed.
Endocrine mucin-producing sweat gland carcinoma, a low-grade adnexal neoplasm may show neuroendocrine differentiation and express neuroendocrine markers, ER, PR, and GATA 3. But it will also express myoepithelial markers, SMA and P63.
Because of presternal presentation, NET arising from the breast needed to be excluded, which will express ER, PR, and GATA3 along with neuroendocrine markers. Thus, distinction is mainly on a clinical and radiological basis.
NET can be categorized into grade 1, 2, and 3 according to mitotic rate and Ki67 index similar to the gastrointestinal NET grading system. In the present case, the mitotic rate was 10 to 12/hpf and Ki67 index was 22% in highly proliferative areas. But still, it was considered a low-grade tumor as local recurrence and distant metastasis are uncommon. The patient is on tamoxifen therapy, without any complications after 1 year of surgery.
To conclude, because of simultaneous presentation of swelling in thyroid and presternal region, medullary carcinoma of thyroid with cutaneous and nodal metastasis was suspected, but later it was revealed to be primary cutaneous NET hence high index of suspicion is needed for these masquerading tumors.
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[Figure 1], [Figure 2]