Scientific Letter
Solitary Pulmonary Nodule as a Form of Presentation of Cryptococcosis in a Renal Transplant Recipient
Nódulo pulmonar solitario como forma de presentación de la criptococosis en el trasplantado renal
Saulo Fernández Granados
, Ernesto Fernández Tagarro, Ana Ramírez Puga, Rita Guerra Rodríguez, César García Cantón
Corresponding author
Servicio de Nefrología, Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria, Las Palmas, Spain
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He attended a routine follow-up visit, where he was seen to be totally asymptomatic, with no suspicious respiratory or infectious clinical symptoms. No significant findings were made on physical examination. Chest X-ray revealed an ovoid lesion in the posterior segment of the right upper lobe (RUL), 12<span class="elsevierStyleHsp" style=""></span>mm in diameter, not observed in the study performed 1 year previously. The lesion was explored in greater depth with a chest CT, which showed a lung nodule suggestive of neoplasm in the RUL (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), consistent with stage IA (T1aN0MX). The PET scan showed pathological uptake of this lesion, so malignancy was suspected. The nodule was resected surgically via an atypical segmentectomy with diagnostic and therapeutic intent.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The histological study reported necrotizing granulomatous inflammation with the presence of small rounded structures, heterogeneous in size and with frequent fragmentation, located predominantly within the cytoplasm with signs indicating budding, grayish or eosinophilic on hematoxylin–eosin staining. Stains performed for fungal structures were positive for periodic acid-Schiff (PAS), Grocott's methenamine-silver, mucicarmin, and Alcian Blue, and negative for Ziehl–Neelsen staining, so morphologically the microorganisms were indicative of cryptococcus.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Microbiological testing was completed with serologies that were negative for both <span class="elsevierStyleItalic">C. neoformans</span> and human immunodeficiency virus antibodies. Brain CT scan showed no pathological findings, so lumbar puncture was not performed and additional antifungal treatment was not started. The patient subsequently made good clinical progress and currently remains totally asymptomatic.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Fungal infections are the third cause of infection in solid organ transplantation.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Specifically, the prevalence of <span class="elsevierStyleItalic">C. neoformans</span> infection in kidney transplantation is low, affecting 0.5%–2.8% of transplanted patients, but it is the third leading cause of fungal infection after <span class="elsevierStyleItalic">Candida</span> spp. and <span class="elsevierStyleItalic">Aspergillus</span> spp.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">C. neoformans</span> is an encapsulated yeast present in soil contaminated with bird and bat droppings.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Infection is acquired by inhalation of the microorganism,<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,4</span></a> and the main form of host defense is innate and T-cell-mediated immunity,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> probably explaining the predisposition to this disease among individuals receiving immunosuppressive treatment.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The most frequent form of infection is reactivation of latent microorganisms acquired in a previous infection.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The annual incidence of cryptococcosis has been calculated at more than 2:1000 renal transplant patients. Some authors believe that the incidence is increasing because of the increased survival of these patients,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> while others, in contrast, report that the incidence remains unchanged.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The mean time between transplantation and the onset of cryptococcosis is 25 to 33 months, so presentation in our case is unusually late (120 months). Mortality is as high as 20%<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and appears to be greater if the infection appears in the first year after transplantation,<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> when mortality is between 20% and 27%.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Clinical manifestations of cryptococcal infection in the transplanted population are often non-specific and depend on the organ involved. Central nervous system (CNS) involvement, such as subacute meningoencephalitis, is the most common form of clinical presentation.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> The second most affected organ is the lung.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The clinical manifestations of this form cover a broad spectrum, from acute processes such as pneumonia or pleuritis to radiological findings in asymptomatic patients, especially single nodule or multiple nodules observed on a routine chest X-ray.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> The importance of this form of presentation lies in the fact that the lung is the gateway to disseminated infection, so an intensive diagnostic and therapeutic approach should be taken even in asymptomatic infection. After clinical reassessment, in the absence of neurologic symptoms, negative brain imaging, lack of uptake in PET testing at other levels, and negative serologies against cryptococcus, disseminated disease and CNS involvement could be excluded in our patient.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Microbiological diagnosis of pulmonary cryptococcosis can be confirmed by culturing the fungus in a sputum sample or by detecting cryptococcal antigen in serum.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Serological detection usually means that the infection is disseminated, which always requires the disease to be ruled out at other levels, especially CNS.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Another way to diagnose this infection, as in the case presented, is by histological study of a biopsy or surgical specimen, demonstrating the presence of encapsulated yeasts with the usual fungal stains such as PAS and Grocott, and especially mucin, mucicarmin and Alcian blue stains, since the <span class="elsevierStyleItalic">Cryptococcus</span> genus is the only frequently pathogenic fungus that produces mucinous capsular material.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Fluconazole may be used in mild forms of cryptococcal lung infection. In severe cases with diffuse pulmonary infiltrates or in the context of disseminated infection, treatment is based on amphotericin B combined with flucytosine.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Surgical treatment, as described, may be indicated in case of diagnostic uncertainty or therapeutic failure. Finally, because infection after transplantation is exceptional and occurs late, antifungal prophylaxis is not indicated.</p><p id="par0060" class="elsevierStylePara elsevierViewall">In conclusion, cryptococcal infection should be considered in the differential diagnosis of SPN in immunocompromised patients, such as the transplanted population, and the diagnostic and therapeutic approach should be proactive as the respiratory tract is considered the gateway to disseminated infection.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Fernández Granados S, Fernández Tagarro E, Ramírez Puga A, Guerra Rodríguez R, García Cantón C. Nódulo pulmonar solitario como forma de presentación de la criptococosis en el trasplantado renal. Arch Bronconeumol. 2020;56:396–398.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 494 "Ancho" => 800 "Tamanyo" => 42848 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Chest CT showing a solitary nodule 1 cm in diameter in the right upper lobe.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Solitary pulmonary nodules: Part I. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 6 | 4 | 10 |
| 2024 October | 45 | 20 | 65 |
| 2024 September | 51 | 19 | 70 |
| 2024 August | 63 | 37 | 100 |
| 2024 July | 41 | 18 | 59 |
| 2024 June | 51 | 29 | 80 |
| 2024 May | 81 | 34 | 115 |
| 2024 April | 30 | 29 | 59 |
| 2024 March | 39 | 20 | 59 |
| 2024 February | 39 | 26 | 65 |
| 2023 March | 5 | 3 | 8 |
| 2023 February | 49 | 19 | 68 |
| 2023 January | 39 | 36 | 75 |
| 2022 December | 50 | 26 | 76 |
| 2022 November | 52 | 18 | 70 |
| 2022 October | 63 | 35 | 98 |
| 2022 September | 28 | 15 | 43 |
| 2022 August | 39 | 48 | 87 |
| 2022 July | 29 | 48 | 77 |
| 2022 June | 25 | 34 | 59 |
| 2022 May | 23 | 28 | 51 |
| 2022 April | 37 | 25 | 62 |
| 2022 March | 39 | 31 | 70 |
| 2022 February | 12 | 14 | 26 |
| 2021 November | 1 | 0 | 1 |
| 2020 October | 2 | 0 | 2 |
| 2020 June | 1 | 0 | 1 |
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