A Pigmented Facial Nodule

A 65-year-old male patient presented in a medicine emergency with a chief complaint of abnormal body movements for two days. The patient was apparently well two months ago, when he started having moderate to severe headaches associated with vertigo, mainly in the occipital region. It was associated with episodes of vomiting. He had a new onset cough with expectoration for four to five days, followed by altered sensorium and two episodes of seizures for two days. A dermatological consult was sought for a cutaneous lesion, which was a dark black to brown coloured crusted nodular lesion, present on the right nasolabial fold [Figure 1]. On palpation, it was firm, non-tender and without any discharge exuding from its surface. The surrounding areas were unremarkable. No group of lymph nodes was palpable. A dermoscopy of the lesion revealed blue–black areas, dark red to yellow crusting and no vascular structures [Figure 2]. On investigation, computed tomography of the brain revealed multiple variable-sized rounds to oval heterogeneously enhancing hypodense lesions with perilesional oedema seen scattered in bilateral cerebral and cerebellar hemispheres, suggestive of infective or metastatic cause [Figure 3]. The CSF examination revealed lymphocytic pleocytosis, low proteins and low sugar levels. FNAC smear of the cutaneous lesion revealed blood admixed hypercellularity, secondary to a yeast form with a central cytoplasmic body and perilesional clear capsule, along with cyst macrophages, few neutrophils and mononuclear cells [Figure 4]. Figure 4b shows the PAS staining findings of the FNAC smear.Figure 1: Dark black to brown, crusted, nodular lesion, measuring 2.7 cm in diameter over the right nasolabial fold. a. Front view b. Right lateral viewFigure 2: Dermoscopy image of the lesion captured by Heine delta 20T dermatoscope in polarised mode (10×) showing irregularly distributed blue–black areas, and red to yellow crustingFigure 3: Computed tomography of the brain (axial sections) revealed multiple variable-sized round to oval heterogeneously enhancing hypodense lesions with perilesional oedema seen scattered in bilateral cerebral and cerebellar hemispheresFigure 4: Cytological smear (400×) of the cutaneous lesion showing hypercellularity, secondary to a yeast form with central cytoplasmic body and perilesional clear capsule a. Giemsa stain b. PAS stainWhat is your diagnosis? Cryptococcosis Discussion The epidemiology of cryptococcosis has continued to evolve around the world from recognition of cryptococcosis as an infection-causing multisystem disease that began in the late nineteenth century, to it then becoming an epidemic of meningeal and respiratory disease during the HIV pandemic in the twentieth century and to the presently reduced number of cases by virtue of the impact of antiretroviral therapies.[1-3] The risk factors for contracting an infection of this sugar-coated yeast are immunosuppression, diabetes, malignancy, liver failure, renal failure, alcoholism, and collagen diseases. However, recently, disseminated cryptococcus infection has been linked to genetic variants in immune genes and subsequent immunological perturbation by producing abundant GM-CSF antibodies in immunocompetent hosts.[4] The primary manifestations of cryptococcosis are due to lung involvement, presenting either as cough, dyspnoea or pleuritic pain. Extrapulmonary cryptococcosis frequently involves CNS, presenting as headache, seizures, hearing loss, photophobia, papillary oedema, cranial nerve palsies and visual disturbances. Similarly, cutaneous manifestations of cryptococcosis are also protean, ranging from a solitary papule, maculopapular lesion with an ulcerated centre, discharging sinus to the underlying deep abscess or the underlying bone, panniculitis, cellulitis and multiple umbilicated papular lesions that can be mistaken for molluscum contagiosum. These cutaneous and mucous membrane lesions occur in about 10–3% of cases, overall, but when present are considered the marker of disseminated disease or systemic spread.[5] However, the term primary cutaneous cryptococcosis is used erroneously to describe a solitary lesion of cryptococcosis on the skin as in many such cases there is evidence of systemic spread, implying that the skin lesion has developed after bloodstream spread from a primary lung focus.[6] The clinical manifestation in the present case was, however, a crusted pigmented lesion, which evolved slowly over eight months over an UV exposed site in an otherwise immunocompetent host. Although no clear source of infection was documented, inoculation after trauma cannot be ruled out in this case, as the nodular lesion started to develop long before the appearance of lung and neurological manifestations. In the already existing literature also, the documented cases of primary cutaneous infection by inoculation are rare and exceptional.[7] The differential diagnoses for cutaneous cryptococcosis are summarized in Table 1.Table 1: Differential diagnoses for cutaneous cryptococcosisThis dialect of already known manifestations and course of disease has led to a fallacious provisional diagnosis of pigmented nodular melanoma and its subsequent metastatic spread to the brain and lungs. The lung and pleura are the most common sites of melanoma metastases and usually the primary sites of initial metastasis, possibly due to the convergence of blood and lymphatic systems, and the peripheral blood pumped from the right heart through the pulmonary artery.[8] Similarly, CNS involvement can be expected in 29% of the patients, while some studies have even demonstrated that 40–60% of patients with metastatic melanoma develop brain metastases at some point in the course of their disease, and one autopsy series identified CNS involvement in up to 80% of patients with metastatic melanoma.[9] In a contrasting anecdote, a per contra report was published by Sun et al.,[10] where the patient was treated for pulmonary fungal infection for eight months with no improvement, only later to be diagnosed as a case of metastatic malignant melanoma. Various modalities used in the treatment of cutaneous cryptococcosis include liposomal amphotericin B, fluconazole, itraconazole, miconazole, ketoconazole and flucytosine alone or in combinations. The cutaneous lesions can be excised in patients who fail or cannot tolerate medical management.[11] Learning points Cryptococcosis is an invasive fungal infection caused by cryptococcus neoformans and related species, mostly in immunosuppressed patients. It has a wide array of clinical as well as cutaneous manifestations, which can sometimes bemuse the treating physician and lead to delay or misdiagnosis of this treatable infection. High index of suspicion and account of all associated systemic features is required for diagnosis of such atypical cases. Dermoscopy can serve as a useful non-invasive screening tool for dermatologists to cut short the list of differential diagnoses. It is always staggering for dermatologists to come across some lesions and cases, which might seem customary, but turn out to be extraordinarily exceptional and thus add to already known clinical manifestations of a disease. Opportunistic fungal infections like cryptococcosis may also present in immunocompetent patients and should always be included in the list of differentials. Primary cutaneous cryptococcal infection due to direct inoculation is rare and cutaneous cryptococcal lesions usually serve as a marker for systemic disease. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.