RESUMEN
Merkel cell carcinoma (MCC) is a rare neoplasm that arises in the skin of elderly patients on sun-exposed areas such as the head, neck, and extremities. Involvement of the epidermis by tumor cells is a relatively uncommon phenomenon. However, a few cases have been reported of Merkel cell carcinoma in situ (MCCIS) in which tumor cells are confined exclusively to the epidermis without dermal involvement. Herein, we present a peculiar MCCIS lesion in a 66-year-old man composed of tumor cells in a nested and lentiginous growth pattern, exhibiting variable quantities of intracytoplasmic dusty brown pigment consistent with melanin, thus closely mimicking melanoma in situ. In addition, the lesion was associated with invasive squamous cell carcinoma, which has not been previously reported in the literature. An extensive search of the PubMed-indexed, English-language literature yielded only 17 case reports of MCCIS without documented invasion in which clinical data were available. Out of the cases with available clinical information, individuals with strict MCCIS (n = 13) showed no evidence of recurrence or metastases. The median follow-up time in the cases with available data (n = 9) was 12 months (mean 12.8 months, range 6-21). Thus, MCCIS without invasion may have a favorable clinical course in contrast to invasive MCC tumors.
Asunto(s)
Carcinoma de Células de Merkel , Carcinoma de Células Escamosas , Melanoma , Neoplasias Cutáneas , Masculino , Humanos , Anciano , Carcinoma de Células de Merkel/diagnóstico , Carcinoma de Células de Merkel/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Melanoma/diagnóstico , Carcinoma de Células Escamosas/patología , Melanoma Cutáneo MalignoRESUMEN
Drosophila melanogaster produces fatty acid amides, and thus, provides a model to unravel the pathways for their biosynthesis. We previously demonstrated that arylalkylamine N-acetyltransferase-like 2 (AANATL2) from D. melanogaster will catalyze the formation of long-chain N-acylserotonins and N-acyldopamines in vitro. Generating silencing RNA via the UAS/GAL4 bipartite approach for targeted gene expression effectively decreased the endogenous levels of the AANATL2 transcripts in D. melanogaster, as shown by reverse transcription quantitative polymerase chain reaction. Consistent with these data, western blot analysis of the offspring of the AANATL2 knockdown flies using an anti-AANATL2 antibody revealed a significant reduction in the expression of the AANATL2 protein. Reduced expression of AANATL2 decreased the cellular levels of N-palmitoyldopamine (PALDA), providing strong evidence that AANATL2 is responsible for the biosynthesis of PALDA in vivo. This is the first time that the expression of an AANAT has been reduced in D. melanogaster to link one of these enzymes to the in vivo production of an N-acylarylalkylamide.
Asunto(s)
Aciltransferasas/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Aciltransferasas/genética , Animales , Dopamina/análogos & derivados , Dopamina/biosíntesis , Proteínas de Drosophila/genética , Drosophila melanogaster/enzimología , Drosophila melanogaster/metabolismo , Silenciador del GenRESUMEN
BACKGROUND: Sinonasal adenosquamous carcinoma is rare, and there are almost no studies detailing morphology or characterizing their genetic driver events. Further, many authors have termed sinonasal tumors with combined squamous carcinoma and glands as mucoepidermoid carcinoma but none have analyzed for the presence of MAML2 rearrangement. METHODS: Cases from 2014 to 2020 were collected and diagnosed using World Health Organization criteria. They were tested for p16 expression by immunohistochemistry (70% cut-off), DEK::AFF2 fusion by fluorescence in situ hybridization (FISH) and AFF2 immunohistochemistry, MAML2 rearrangement by FISH, and low- and high-risk HPV by RNA ISH and reverse transcription PCR, respectively. Detailed morphology and clinical features were reviewed. RESULTS: There were 7 male (64%) and 4 female (36%) patients with a median age of 69 years, most Caucasian (10 of 11 or 91%). Most had tobacco exposure (8/11, 73%) and most presented with epistaxis, a visible nasal mass, and/or facial pain. Several had a precursor papillomas (3 of 11, 27%). The squamous component had variable keratinization, 5 of 11 (46%) of which would be described as keratinizing, 3 non-keratinizing, and 2 with mixed features. All had gland formation, by definition, and 2 of 11 (18%) had ciliated tumor cells. None of the 11 cases had MAML2 rearrangement and one had DEK::AFF2 fusion with associated positive nuclear AFF2 protein immunostaining. Most were p16 positive (7 of 11, 64%) and all 7 of these were hrHPV positive either by RNA ISH or RT-PCR. Two of the p16-negative tumors were positive for lrHPV by RNA ISH. Treatment included surgery alone (4 of 11, 36%), surgery with adjuvant radiation (5 of 11, 45%), and surgery with radiation and chemotherapy (2 of 11, 18%). Four of 11 patients (36%) suffered disease recurrence, two requiring re-operation and who were disease free at last follow-up, one receiving additional chemotherapy and who was alive with disease. The other elected to undergo palliative therapy and died of disease. CONCLUSION: Sinonasal adenosquamous carcinoma is a somewhat heterogeneous tumor not infrequently arising ex papilloma and having various drivers including high- and low-risk HPV and rarely DEK::AFF2 fusion. The prognosis appears favorable when proper treatment is possible.
Asunto(s)
Carcinoma Adenoescamoso , Carcinoma Mucoepidermoide , Infecciones por Papillomavirus , Neoplasias de los Senos Paranasales , Humanos , Masculino , Femenino , Anciano , Carcinoma Adenoescamoso/patología , Virus del Papiloma Humano , ARN Mensajero , Hibridación Fluorescente in Situ , Infecciones por Papillomavirus/complicaciones , Factores de Transcripción/genética , Proteínas Nucleares/genética , Neoplasias de los Senos Paranasales/genética , Neoplasias de los Senos Paranasales/patología , Carcinoma Mucoepidermoide/patología , Transactivadores/genéticaRESUMEN
Patients can be seen where "fungal debris," "mycetoma," or "mass-like obstruction" of the sinonasal tract is suspected clinically but lack fungus and instead have granular, eosinophilic debris and bacterial colonies. We report and characterize 15 such cases, tentatively termed "bacteromas," compared with randomly selected cases of mycetoma and allergic fungal sinusitis (AFS). Pathology reports from 2016 to 2021 were searched. All candidate cases were examined microscopically and included if they had granular, amorphous debris with negative Grocott methenamine silver staining and lacked diagnostic features of other entities. The 7 males and 8 females ranged from 21 to 78 years old. Imaging frequently revealed opacification of the paranasal sinuses. Operative reports showed all to have paranasal sinus involvement. Most were unilateral (13/15, 87%). The maxillary sinus was involved in 11/15 (73%) cases, sphenoid sinus in 2/15 (13%), and frontal and ethmoid sinuses in 1/15 (7%), each. Bacteroma patients frequently had a history of allergic rhinitis (8/15, 53%), more than mycetomas (1/15, 7%) and AFS (5/15, 33%) ( P =0.0142). Facial pain was a common presenting symptom (13/15, 87%) in bacteromas compared with mycetomas (5/15, 33%) or AFS (1/15, 7%). Morphologically, cases consisted of large aggregates of paucicellular to acellular debris with a characteristic densely eosinophilic granular appearance, commonly associated with bacteria. Four of the 10 cultured patients grew Pseudomonas aeruginosa . Course posttreatment ranged from symptom resolution 1 week postoperatively to recurrent infections and symptoms 23 months from the initial operation. In summary, "bacteroma" is a heretofore undescribed pathologic entity of the sinuses that appears to be related to chronic bacterial infection and is distinct from mycetoma, AFS, and rhinolithiasis.