Final Diagnosis -- Metastatic pulmonary adenocarcinoma to a diffuse astrocytoma


Intracranial tumor-to-tumor metastasis: Metastatic pulmonary adenocarcinoma to a diffuse astrocytoma (WHO grade II).


Two pathologic phenomenon, "collision tumor" and "tumor to tumor metastasis" both result in the intermingling of two separate primary neoplasms. While "collision tumor" results from growth of neighboring tumors within a shared space, "tumor to tumor metastasis" results from hematogenous spread of a primary donor usually extracranial tumor to a recipient/host tumor. The criteria used to defined "tumor to tumor metastasis" are as follows: (i) more than one primary tumor must exist; (ii) the recipient tumor must be a true neoplasm; (iii) the metastatic neoplasm should show established growth in the recipient tumor, not resulting from contiguous growth of an adjacent tumor or tumor embolism; and (iv) lymphatic metastasis to a site of pre-existing lymphoid malignancy are excluded (1, 7). Tumor to tumor metastasis is an unusual phenomenon. The most common donor tumors are breast and lung carcinoma (7),while the most common benign and malignant recipient tumors are meningioma and renal cell carcinoma, respectively (7, 10). Metastasis to primary intracranial glioma is exceptionally rare and to our knowledge represents the first report of metastatic carcinoma to an IDH1mutant low-grade diffuse glioma (9). To date, 14 cases of tumor metastasis to glioma, including our case, have been reported in the literature (5-8). The three most common donors are lung carcinoma, melanoma, and breast carcinoma in descending order. The top three most common recipients are oligodendroglioma, anaplastic astrocytoma, and ependymoma. Nonetheless, some of the older reports are questionable and poorly substantiated given the lack of immunohistochemical and genetic tools of those times. For example, malignant epithelioid cells could represent epithelial-like areas or frank epithelial metaplasia within an anaplastic astrocytoma or glioblastoma (2, 6). Similarly, without appropriate immunohistochemical confirmation, metastatic melanoma may occasionally mimic diffuse glioma (6). Although in general, the pathogenesis of cancer metastasis has been described using the "seed and soil" hypothesis (3, 4), there are currently no proven molecular explanations for "tumor-to-tumor metastasis" and why gliomas so rarely serve as recipients in this phenomenon.


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  2. Kleihues P, Burger PC, Aldape KD, Brat DJ, Biernat W, Bigner DD (2007) Glioblastoma. In: WHO Classification of tumours of the central nervous system, Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds), pp 33-49, IARC: Lyon
  3. Langley RR, Fidler IJ (2011) The seed and soil hypothesis revisited-The role of tumor-stroma interactions in metastasis to different organs. Int J Cancer 128:2527-2535
  4. Mathot L, Stenninger J (2012) Behavior of seeds and soil in the mechanism of metastasis: a deeper understanding. Cancer Sci 103:626-631.
  5. Mizutani H, Suzuki H, Wakabayashi S, Mitake A, Mizutani M, Banno T, Oba S, Tada T, Kuhara H (1987) A case of metastasis from a colon carcinoma to an intracranial oligodendroglioma. Gan No Rinsho 33:1733-1739.
  6. Mörk SJ, Rubinstein LJ (1988) Metastatic carcinoma to glioma: a report of three cases with a critical review of the literature. J Neurol Neurosurg Psychiatry 51:256-259.
  7. Takei H, Powell SZ (2009) Tumor-to-tumor metastasis to the central nervous system. Neuropathology 29:303-308.
  8. Tally PW, Laws ER Jr, Scheithauer BW (1988) Metastases of central nervous system neoplasms. Case report. J Neurosurg 68:811-816.
  9. Rivera-Zengotita M, Yachnis AT (2012) Gliosis versus glioma?: don't grade until you know. Adv Anat Pathol 19:239-249.
  10. Zhou Q, Chang H, Gao Y, Cui L (2013) Tumor-to-tumor metastasis from pituitary carcinoma to radiation-induced meningioma. Neuropathology 33:209-212

Contributed by Jantima Tanboon, MD, Ananya Pongpaibul, MD, Orasa Chawalparit, MD, Jitladda Wasinrat, MD, Theerapol Witthiwej, MD, Arie Perry, MD

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