Colorectal cancers (CRCs) initiate through distinct mutations, including in APC pathway components leading to tubular adenomas (TAs); in BRAF, with epigenetic silencing of CDX2, leading to serrated adenomas (SAs); and in the DNA mismatch repair machinery driving microsatellite instability (MSI). Transformation through the APC pathway involves loss of the hormone GUCA2A that silences the tumor-suppressing receptor GUCY2C. Indeed, oral hormone replacement is an emerging strategy to reactivate GUCY2C and prevent CRC initiation and progression. Moreover, retained expression by tumors arising from TAs has established GUCY2C as a diagnostic and therapeutic target to prevent and treat metastatic CRC. Here, we defined the potential role of the GUCA2A-GUCY2C axis and its suitability as a target in tumors arising through the SA and MSI pathways. GUCA2A hormone expression was eliminated in TAs, SAs, and MSI tumors compared to their corresponding normal adjacent tissues. In contrast to the hormone, the tumor-suppressing receptor GUCY2C was retained in TA and MSI tumors. Surprisingly, GUCY2C expression was nearly eliminated in SAs, reflecting loss of the transcription factor CDX2. Changes in the GUCA2A-GUCY2C axis in human SAs and MSI tumors were precisely recapitulated in genetic mouse models. These data reveal the possibility of
Heparin is one of the most widely prescribed medications. Cutaneous reactions distant to the injection site are rare and under-reported in the literature. We present an elderly man with history of CNS lymphoma who underwent treatment of a deep venous thrombosis with enoxaparin and subsequently developed well demarcated bullous lesions within days of heparin initiation. The exact pathophysiology is not well understood. Hemorrhagic bullous dermatosis is a rare cutaneous reaction that is temporally associated with the initiation of heparin products. The handful of cases thus far suggest that regression of these seemingly benign lesions may or may not be associated with dose reduction or discontinuation of heparin products and typically occur within a few weeks. Elderly age appears to be one potential risk factor for development of these rare asymptomatic lesions. Malignancy may have some contributing factor and differentiation between this rare cutaneous manifestation from heparin products and other dermatological findings in patients with malignancy is key. Because of the asymptomatic and self-limiting nature of hemorrhagic bullous dermatoses in the setting of heparin product use, we presume that the reported incidence does not reflect true clinical practice.
Spinal paragangliomas (SP) are benign and overall rare extra-adrenal neuroendocrine tumors often diagnosed during workup for lower back pain. Complete surgical resection achieves both symptomatic relief and cure. We present a 32-year-old man with a longstanding history of lumbago and bilateral lower extremity pain found to have a lumbar paraganglioma at the level of the L3 vertebrae. The clinical, histopathological, and radiological characteristics are described, including the rare finding of superficial siderosis on MRI of the brain. A laminectomy with microscopic dissection of the intradural mass achieved complete debulking without evidence of residual tumor. Excellent prognosis can be achieved with complete surgical resection of SP without the need for adjuvant therapy. Therefore, care should be taken to distinguish these spinal tumors from those that appear similar but are more aggressive. As such, the radiological finding of superficial siderosis should raise the suspicion for SP when a vascular intradural extramedullary spinal tumor is observed.
BACKGROUND Metastases to the central nervous system are often multiple in number and typically favor the gray-white matter junction. Collision tumors, defined as the coexistence of two morphologically different tumors, such as metastases to a known pituitary adenoma (PA), are exceedingly rare. Only a few reported cases of metastases to a PA exist in the literature. OBSERVATIONS The authors present the case of a 64-year-old man with a known history of stage IV metastatic melanoma who was found to have hypermetabolic activity in the sellar region on surveillance positron emission tomography. On laboratory evaluation, he had clear evidence of pituitary axis dysfunction without diabetes insipidus. Subsequent magnetic resonance imaging showed a 2.4-cm sellar mass with features of a pituitary macroadenoma and internal hemorrhage, although no clinical symptoms of apoplexy were noted. He underwent a transsphenoidal endoscopic endonasal approach for resection of the sellar lesion. Final pathology showed a collision tumor with melanoma cells intermixed with PA cells. LESSONS Histological analysis verified the rare presence of a collision tumor of a melanoma metastasis to a nonfunctional pituitary macroadenoma. Metastasis to a preexisting PA, although rare, should be considered in the differential diagnosis in patients with sellar lesions and a known cancer history.
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