title: Combined small-cell carcinoma of the lung with quadripartite differentiation of epithelial, neuroendocrine, skeletal muscle, and myofibroblastic type.
abstract: The combined variant of small-cell lung carcinoma (SCLC) refers to the variable admixture of small cell and non-small cell carcinoma, whereas the association with sarcoma or sarcoma-like elements is exceedingly rare. A 76-year-old Caucasian man underwent right upper lobectomy with regional lymphadenectomy because of a symptomatic 7 cm-sized tumor mass. Formalin fixed-paraffin embedded material was used to highlight several differentiation cell lineages by means of immunohistochemistry, electron microscopy, and mutational assay. The tumor was discovered as being IIB stage (pT2b pN1(1/51) pM0) and featured biphasic appearance with close intermingling of SCLC (40%) and collagen-rich spindle cell sarcoma (60%). Epithelial (cytokeratins, TTF-1), neural (neurofilaments, GFAP), endocrine (chromogranin, synaptophysin, CD56), and skeletal muscle (desmin, sarcomeric actin, myogenin) markers were variably co-expressed by SCLC elements, whereas mesenchymal (vimentin), smooth muscle (actin, myosin, H-caldesmon, calponin), fibroblastic (CD10), and, more focally, skeletal muscle (desmin, sarcomeric actin and myogenin) markers were highlighted in the spindle cell sarcoma elements. TP53 codon V274F mutation in exon 8 was shared by either cell component. After undergoing adjuvant chemotherapy, the patient is currently alive and well at the 40-month follow-up. To the best of our knowledge, this is the first report of combined SCLC with quadripartite differentiation of epithelial, neuroendocrine, skeletal muscle, and myofibroblastic type, somewhere at the level of the same individual tumor cells. This tumor had probably derived for clonal evolution of a p53-mutated common ancestor lesion.
authors.affiliation: Division of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy. giuseppe.pelosi@istitutotumori.mi.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pelosi
authors.forename: Angelica
authors.initials: A
authors.lastname: Sonzogni
authors.forename: Domenico
authors.initials: D
authors.lastname: Galetta
authors.forename: Federica
authors.initials: F
authors.lastname: Perrone
authors.forename: Paola
authors.initials: P
authors.lastname: Braidotti
authors.forename: Michela
authors.initials: M
authors.lastname: Manzotti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fabbri
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Spaggiari
authors.forename: Giulia
authors.initials: G
authors.lastname: Veronesi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D002454:Cell Differentiation; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004847:Epithelial Cells / Q000473:pathology; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D008297:Male; D046529:Microscopy, Electron, Transmission; D018482:Muscle, Skeletal / Q000473:pathology; D058628:Myofibroblasts / Q000473:pathology; D009367:Neoplasm Staging; D009490:Neurosecretory Systems / Q000473:pathology; D011013:Pneumonectomy; D055752:Small Cell Lung Carcinoma / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D012907:Smoking / Q000009:adverse effects
chemical_list: D014408:Biomarkers, Tumor; D005047:Etoposide; D002945:Cisplatin