pPNETs belong to the family of “small round cell tumors” that show varying degrees of neuroectodermal differentiation and are derived from cells originating from the neural crest  and are characterized by a specific chromosomal translocation, t(11;22)(q24;q12), in most cases. Among the reported cases of PNET, tumors involving the thoracopulmonary region were first reported as “malignant small cell tumors of the thoracopulmonary region in childhood” by Askin et al. in 1979, which led to these tumors being referred to as Askin’s tumors .
Conventional light microscopy analysis of PNETs shows undifferentiated small, round cells with uniform, unconspicuous nuclei and scanty cytoplasm arranged in lobules with rosettes and pseudorosettes formation; in addition, there is little or no stroma. Immunohistochemically, PNETs are positive for CD99 antigen, but CD99 immunostaining is not specific and the results must be interpreted in combination with other findings. T lymphoblastic lymphoma, poorly differentiated synovial sarcomas, stromal tumors, and rare rhabdomyosarcoma may show CD99 positivity. Vimentin stains most tumor cells and neural markers, such as NSE, and is frequently expressed by tumor cells . Cytokeratin-positive staining has also been reported in some cases of primitive neuroectodermal tumors . To diagnose a tumor as PNET, it should display small round cells forming rosette and pseudorosettes, and should be positive for at least two of the neural markers. Ultrastructural analysis usually shows PNET cells to have complex cytoplasmic processes, microtubules, and few neurosecretory granules. The following chromosomal translocations have been associated with PNET specimens: t(21;22)(q22;q12), t(11;22)(q24;q12), t(7;22)(p22;q12), and t(7;22)(q22;q12) . Thus, the diagnosis of PNET necessitates histopathological, immunohistochemical, ultrastructural, and, if possible, genetic analyses.
The differential diagnosis of PNETs includes neuroblastoma, lymphoma, small-cell carcinoma, rhabdomyosarcoma, monophasic synovial sarcoma, and desmoplastic small round cell tumor, all of which are indistinguishable by conventional light microscopy . However, due to the different prognostic characteristics and therapeutic schedules for each of these tumor types, differential diagnoses are essential. Immunohistochemical positivity for CD99, NSE, synaptophysine, and chromogranine A are very useful in differential diagnosis. Furthermore, the presence of Homer-Wright rosettes are typical for neuroblastomas, which are also positive for NSE, synaptophysine, and chromogranine A, but negative for CD99. LCA positivity supports the diagnosis of lymphoma, but T cell lymphoblastic lymphoma may be negative for LCA and positive for CD99 and CD3. Small-cell carcinoma is almost always positive for cytokeratin, while rhabdomyosarcoma is positive for desmin, actin, myoglobulin, and monophasic synovial sarcoma is positive for CD99, cytokeratin , EMA. The desmoplastic small round cell tumor is characterized by sharply circumscribed nests or clusters of small, undifferentiated cells surrounded by a desmoplastic stroma, and show positivity for cytokeratin and desmin, but negativity for CD99. Therefore, the phenotypes observed in our case, i.e., positive expression of CD99, vimentin, NSE, and synaptophysin, and negative expression of cytokeratins, CD3, desmin, and LCA, are highly suggestive of a pulmonary PNET [3, 9–11].
Despite the patient’s history of pulmonary PNET and imaging findings that were consistent with primary pancreatic cancer, we initially suspected primary serous cystic pancreatic neoplasm because metastasis of a PNET to the pancreas had never been previously reported. However, the patient’s histological findings indicated no transition had occurred from the pancreas to the neoplastic tissue. In addition, there were no clinical signs of chronic pancreatitis in the surrounding parenchyma. Considering the expression of CD99, NSE, and synaptophysine, as well as the primary pulmonary PNET, we believed the findings strongly supported a diagnosis of metastatic pancreatic PNET.
According to the literature, there have only been nine reported cases of PNET originating from the lung without pleural or chest wall involvement [9, 12–17]. Ages of the reported patients have ranged between 8 to 67 years, with a mean age of 33 years. There is a slight male predominance, with the male:female ratio being 5:4. Five of the cases originated from the left lung and four from the right. Despite treatment with various combinations of surgery, chemotherapy, and radiation therapy, the survival rate in the previous reports was poor; typically, the two-year survival rate after operation is 33.3%. Of the nine reported cases, seven were followed-up; four were alive without disease at eight months, 16 months, 22 months and two years after surgery, and three had died at three months, two years, and two years after operation due to local recurrence or widespread metastatic disease. Furthermore, the predominating metastatic sites are the lungs, adrenal glands, and ovaries. In our case, no adjunct radiation or chemotherapy was given after the initial surgery, due to patient refusal. However, recurrence was detected at sixteen months after the first resection and appeared as a metastasis to the pancreas. The patient underwent the second radical surgical resection of the metastatic tumor. Adjunct radiation or chemotherapy again refused by the patient after the second surgery. To date, no evidence of tumor recurrence or metastasis has emerged. The patient has survived 32 months after the second surgery. The long-term survival of the patient may have been a result of the two radical surgeries alone, but we believe that his prognosis would have been better if the lung biopsy was performed promptly in October 2005. We speculate that close follow-up with immediate surgical intervention when required may have helped to prolong the survival of our case .