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Impressive Response to Dose-Dense Chemotherapy in a Patient with NUT Midline Carcinoma.

Maur M, Toss A, Dominici M, Frassoldati A, Corradini P, Maiorana A, Fontana A, Conte P - Am J Case Rep (2015)

Bottom Line: In a few days, the patient developed a superior vena cava syndrome and an acute respiratory failure.In the meantime, the diagnosis of NMC was confirmed.A surprising clinical benefit was obtained after the first cycle of chemotherapy, and after 6 cycles a PET-CT scan showed a very good response.

View Article: PubMed Central - PubMed

Affiliation: Division of Oncology, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of Modena and Reggio Emilia, Modena, Italy.

ABSTRACT

Background: NUT midline carcinoma (NMC) is a rare, highly lethal malignancy that results from a chromosome translocation and mostly arises in the midline organs. To date, no treatment has been established. Most patients receive combinations of chemotherapy regimens and radiation, and occasionally subsequent resection; nevertheless, patients have an average survival hardly exceeding 7 months.

Case report: A 21-year-old patient was admitted to our division with a large mediastinal mass with lung nodules, multiple vertebral metastases, and massive nodal involvement. In a few days, the patient developed a superior vena cava syndrome and an acute respiratory failure. Due to the rapid course of the disease, based on preliminary histology of poorly differentiated carcinoma, a dose-dense biweekly chemotherapy with paclitaxel, ifosfamide, and cisplatin was started. In the meantime, the diagnosis of NMC was confirmed. A surprising clinical benefit was obtained after the first cycle of chemotherapy, and after 6 cycles a PET-CT scan showed a very good response. At this point, radiotherapy was started but the disease progressed outside of the radiation field. The patient entered into a compassionate use protocol with Romidepsin, but a PET/CT scan after the first course showed disease progression with peritoneal and retroperitoneal carcinosis. A treatment with Pemetrexed was then started but the patient eventually died with rapid progressive disease.

Conclusions: Our case history adds some interesting findings to available knowledge: NMC can be chemosensitive and radiosensitive. This opens the possibility to study more aggressive treatments, including high-dose consolidation chemotherapy and to evaluate the role of biological agents as maintenance treatments.

No MeSH data available.


Related in: MedlinePlus

On hematoxylin-eosin staining, the neoplasia consisted of round (A ×20) and spindle (B ×20) atypical cells of large size, with prominent nucleoli, expressing cytokeratins (poorly differentiated carcinomas). Cytokeratins are pointed out by monoclonal broad spectrum antibody MNF116 and by monoclonal anticytokeratin antibody CK7 (C ×20), directed against low-molecular weight cytokeratins. The immunoreaction for anti-NUT (nuclear protein in testis) is positive in most of neoplastic cells (D ×20).
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f2-amjcaserep-16-424: On hematoxylin-eosin staining, the neoplasia consisted of round (A ×20) and spindle (B ×20) atypical cells of large size, with prominent nucleoli, expressing cytokeratins (poorly differentiated carcinomas). Cytokeratins are pointed out by monoclonal broad spectrum antibody MNF116 and by monoclonal anticytokeratin antibody CK7 (C ×20), directed against low-molecular weight cytokeratins. The immunoreaction for anti-NUT (nuclear protein in testis) is positive in most of neoplastic cells (D ×20).

Mentions: In the meantime, more detailed histochemical analyses were completed describing a mixture of necrotic and viable cells of variable size with high nuclear/cytoplasmic ratio and MIB-1 expression of approximately 60%. The majority of cells were dyshesive, with some focal cohesive growth pattern and no clear differentiation (Figure 2). A focal positivity was detected for cytokeratin 7 (CK7), Mouse Monoclonal Anti-Cytokeratin 1 Antibody (MNF116), protein 63 (p63), CD10, and CD34. Molecular testing for the SYT gene rearrangement (18q11.2) by FISH, for the Epstein-Barr virus (EBV) (EBER probe) by in situ hybridization (ISH), for mutational status of the Epidermal Growth Factor Receptor (EGFR) (exons 18,19,21) and the Kirsten Rat Sarcoma Viral Oncogene Homolog (K-RAS) (exon 2) were all negative. On the basis of the clinical presentation, the rapid disease course and the histology, a diagnosis of NMC was suggested. Thus, NUT-fusion protein expression linked to the translocation t(15;19) was tested by a specific anti-NUT antibody. The immunohistochemistry confirmed the hypothesis with 80% of nuclei showing a positive signal.


Impressive Response to Dose-Dense Chemotherapy in a Patient with NUT Midline Carcinoma.

Maur M, Toss A, Dominici M, Frassoldati A, Corradini P, Maiorana A, Fontana A, Conte P - Am J Case Rep (2015)

On hematoxylin-eosin staining, the neoplasia consisted of round (A ×20) and spindle (B ×20) atypical cells of large size, with prominent nucleoli, expressing cytokeratins (poorly differentiated carcinomas). Cytokeratins are pointed out by monoclonal broad spectrum antibody MNF116 and by monoclonal anticytokeratin antibody CK7 (C ×20), directed against low-molecular weight cytokeratins. The immunoreaction for anti-NUT (nuclear protein in testis) is positive in most of neoplastic cells (D ×20).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4492486&req=5

f2-amjcaserep-16-424: On hematoxylin-eosin staining, the neoplasia consisted of round (A ×20) and spindle (B ×20) atypical cells of large size, with prominent nucleoli, expressing cytokeratins (poorly differentiated carcinomas). Cytokeratins are pointed out by monoclonal broad spectrum antibody MNF116 and by monoclonal anticytokeratin antibody CK7 (C ×20), directed against low-molecular weight cytokeratins. The immunoreaction for anti-NUT (nuclear protein in testis) is positive in most of neoplastic cells (D ×20).
Mentions: In the meantime, more detailed histochemical analyses were completed describing a mixture of necrotic and viable cells of variable size with high nuclear/cytoplasmic ratio and MIB-1 expression of approximately 60%. The majority of cells were dyshesive, with some focal cohesive growth pattern and no clear differentiation (Figure 2). A focal positivity was detected for cytokeratin 7 (CK7), Mouse Monoclonal Anti-Cytokeratin 1 Antibody (MNF116), protein 63 (p63), CD10, and CD34. Molecular testing for the SYT gene rearrangement (18q11.2) by FISH, for the Epstein-Barr virus (EBV) (EBER probe) by in situ hybridization (ISH), for mutational status of the Epidermal Growth Factor Receptor (EGFR) (exons 18,19,21) and the Kirsten Rat Sarcoma Viral Oncogene Homolog (K-RAS) (exon 2) were all negative. On the basis of the clinical presentation, the rapid disease course and the histology, a diagnosis of NMC was suggested. Thus, NUT-fusion protein expression linked to the translocation t(15;19) was tested by a specific anti-NUT antibody. The immunohistochemistry confirmed the hypothesis with 80% of nuclei showing a positive signal.

Bottom Line: In a few days, the patient developed a superior vena cava syndrome and an acute respiratory failure.In the meantime, the diagnosis of NMC was confirmed.A surprising clinical benefit was obtained after the first cycle of chemotherapy, and after 6 cycles a PET-CT scan showed a very good response.

View Article: PubMed Central - PubMed

Affiliation: Division of Oncology, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of Modena and Reggio Emilia, Modena, Italy.

ABSTRACT

Background: NUT midline carcinoma (NMC) is a rare, highly lethal malignancy that results from a chromosome translocation and mostly arises in the midline organs. To date, no treatment has been established. Most patients receive combinations of chemotherapy regimens and radiation, and occasionally subsequent resection; nevertheless, patients have an average survival hardly exceeding 7 months.

Case report: A 21-year-old patient was admitted to our division with a large mediastinal mass with lung nodules, multiple vertebral metastases, and massive nodal involvement. In a few days, the patient developed a superior vena cava syndrome and an acute respiratory failure. Due to the rapid course of the disease, based on preliminary histology of poorly differentiated carcinoma, a dose-dense biweekly chemotherapy with paclitaxel, ifosfamide, and cisplatin was started. In the meantime, the diagnosis of NMC was confirmed. A surprising clinical benefit was obtained after the first cycle of chemotherapy, and after 6 cycles a PET-CT scan showed a very good response. At this point, radiotherapy was started but the disease progressed outside of the radiation field. The patient entered into a compassionate use protocol with Romidepsin, but a PET/CT scan after the first course showed disease progression with peritoneal and retroperitoneal carcinosis. A treatment with Pemetrexed was then started but the patient eventually died with rapid progressive disease.

Conclusions: Our case history adds some interesting findings to available knowledge: NMC can be chemosensitive and radiosensitive. This opens the possibility to study more aggressive treatments, including high-dose consolidation chemotherapy and to evaluate the role of biological agents as maintenance treatments.

No MeSH data available.


Related in: MedlinePlus