A 68-year-old Chinese man presented with proptosis, epiphora and discomfort in the right eye associated with impaired visual acuity. Contrast computed tomography scan revealed a 3.3 cm × 2.1 cm heterogeneously enhancing mass at the superotemporal aspect of the right orbit with displacement of the lateral rectus muscle (Fig 1). A pigmented tumour with dense adhesions to the surrounding structures was found in orbitotomy with leakage of the pigmented content upon surgical exploration. The lesion was excised as much as possible. Detailed clinical examination showed no evidence of intraocular melanoma, conjunctival or eyelid melanoma, or melanoma anywhere else. Systemic examination and whole-body positron emission tomography-computed tomography scan were unremarkable. The patient was alive with no evidence of disease at 9-month follow-up.

The tumour was a solid, dark brownish multinodular mass covered by fat and skeletal muscle, comprising lobulated sheets of epithelioid and spindly melanocytes with vesicular chromatin, prominent nucleoli, and variable amounts of melanin pigment (Figs 2, 3, and 4). The mitotic count was 1 per 10 HPFs. The neoplastic melanocytes were positive for S100 and SOX10 but negative for BRAF. BRCA1-associated protein 1 immunostaining was intact. Sanger sequencing revealed a GNA11 Q209L mutation. No mutation was found in GNAQ, NRAS, KRAS, BRAF or KIT.

Ocular melanoma most frequently involves the uveal tract (choroid, ciliary body, and iris) and the conjunctiva, where melanocytes are normally present. According to The Cancer Genome Atlas uveal melanoma project, mutually exclusive mutations in GNAQ, GNA11, CYSLTR2 and PLCB4 are the tumour-initiating mutations whereas BAP1, EIF1AX and SF3B1/SRSF2 mutations are associated with prognosis in uveal melanoma.1 In contrast, conjunctival melanoma typically exhibits BRAF, NRAS and NF1 mutations of the MAPK pathway with UV-induced C→T mutation signature.2 Orbital soft tissue melanoma is uncommon with >90% representing secondary tumours as a result of contiguous spread or metastasis from uveal, conjunctival, cutaneous or sinonasal melanomas.3 Primary orbital melanoma is exceedingly rare and has been postulated to arise in embryological remnants of melanocytes arrested in the region since a substantial proportion of cases are associated with blue nevus, orbital melanocytosis or oculodermal melanocytosis (nevus of Ota). Alternatively, it may arise from isolated melanocytes found in the optic nerve sheath, orbital fat, extraocular muscles or orbital periosteum. The majority of patients are white Europeans in their fourth to fifth decade. Histologically, it comprises epithelioid, spindle or mixed populations of neoplastic melanocytes that are frequently pigmented but with a lesser degree of nuclear pleomorphism than their cutaneous and mucosal counterparts. The prognosis is generally poor but a small proportion of patients survive long term. The most frequent site of metastasis is the liver.3 4 The clinicopathological features of primary orbital melanoma are very similar to those of uveal melanoma. The findings of GNAQ, SF3B1, EIF1AX mutations5 and GNA11 mutation in this case provide further evidence that primary orbital melanoma has a close pathogenic relationship with uveal melanoma.

All authors contributed to the concept or design of the study, acquisition of the data, analysis or interpretation of the data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

As an adviser of the journal, HKL Yuen was not involved in the peer review process. Other authors have disclosed no conflicts of interest.

This case was presented as a poster at the Annual Scientific Meeting of The College of Ophthalmologists of Hong Kong and Hong Kong Ophthalmological Society on 14 to 15 December 2019.

This pictorial medicine paper received no specific grant from any funding agency in the public, commercial, or not-forprofit sectors.

The patient was treated in accordance with the tenets of the Declaration of Helsinki. Informed consent was obtained from the patient.

References

1. Bakhoum MF, Esmaeli B. Molecular characteristics of uveal melanoma: insights from the Cancer Genome Atlas (TCGA) Project. Cancers (Basel) 2019;11:1061.Crossref

2. Swaminathan SS, Field MG, Sant D, et al. molecular characteristics of conjunctival melanoma using whole-exome sequencing. JAMA Ophthalmol 2017;135:1434-7. Crossref

3. Rose AM, Luthert PJ, Jayasena CN, Verity DH, Rose GE. Primary orbital melanoma: presentation, treatment, and long-term outcomes for 13 patients. Front Oncol 2017;7:316. Crossref

4. Shields JA, Shields CL. Orbital malignant melanoma: the 2002 Sean B Murphy lecture. Ophthalmic Plast Reconstr Surg 2003;19:262-9. Crossref

5. Rose AM, Luo R, Radia UK, et al. Detection of mutations in SF3B1, EIF1AX and GNAQ in primary orbital melanoma by candidate gene analysis. BMC Cancer 2018;18:1262. Crossref

A 65-year-old Chinese woman was referred to the ophthalmology clinic complaining of grittiness in both eyes for 1 month. She had been diagnosed with stage IV metastatic pulmonary adenocarcinoma with positive mutation in epidermal growth factor receptor (EGFR) gene (L858R) and had been prescribed erlotinib 4 months previously as palliative treatment (Table).

Physical examination revealed bilateral long thick curly eyelashes (Figs 1 and 2) affecting all four eyelids. A papulopustular rash over the periocular region was also evident. The patient denied use of topical prostaglandin analogue for either medical or cosmetic use. A diagnosis was made of drug-induced trichomegaly. Corneal punctate epithelial erosion as a result of the misdirected lashes was treated symptomatically with regular epilation and topical lubricants.

Upon follow-up, gradual partial reversal of trichomegaly was evident at 6 weeks after erlotinib cessation. There was also improvement of the periorbital papulopustular rash. The reversal of trichomegaly after EGFR inhibitor cessation is not well documented in the literature. This case illustrates the presentation and partial resolution of drug-induced trichomegaly.

Eyelash trichomegaly is a rare condition characterised by increase in length, thickness, pigmentation, and curling of the eyelashes. The eyelash follicle, just as the scalp hair follicle, undergoes the cycle of anagen, catagen, and telogen phase. The anagen phase of eyelashes (ie, the growth phase) typically spans 8 weeks in Asian patients and occurs in 18% of eyelashes at any given time.1

Drug-induced trichomegaly is the most common form of trichomegaly to present in a general ophthalmology setting. Prostaglandin analogues such as latanoprost and bimatoprost, although commonly used as antiglaucomatous drugs, are well known for their side-effect of eyelash trichomegaly. The effect is due to up-regulation of prostaglandin E2, D2 receptor expressed in hair follicles.2

The occurrence of EGFR inhibitor–induced trichomegaly is seen less often but is not uncommon in the ophthalmology setting. It has been postulated that EGFR inhibitors inactivate the nuclear factor of activated T-cells. This leads to activation of stem cell bulge and suprabulbar region of the eyelash hair follicles.3 In a typical course, trichomegaly develops between the second and fifth month of EGFR inhibitor treatment.4 An Asian study reported that 2% of patients prescribed EGFR inhibitor treatment had trichomegaly.5 The EGFR inhibitor is also well known to cause a series of cutaneous adverse effects known as the PRIDE syndrome (papulopustules and/or paronychia, regulatory abnormalities of hair growth, itching, and dryness).6 In this case, the patient exhibited PRIDE syndrome affecting the periocular skin as demonstrated in Figures 1 and 2.

Trichomegaly is a benign condition, but long misdirected lashes may lead to corneal punctate epithelial erosion and corneal abrasion. Frequent trimming, epilation, and topical lubricants serve as first-line treatment. Electro-epilation or cryoablation directed at the affected hair follicles may be considered in instances of recurrent misdirected lashes with corneal complications such as infective corneal ulcer.

This case highlights the clinical course of EGFR inhibitor–induced trichomegaly upon cessation of drug therapy, which is not well documented in the literature. Partial reversal of trichomegaly was achieved after stopping erlotinib for 6 weeks. It is evident that the time required for trichomegaly resolution follows the typical eyelash follicle cycle.

All authors contributed to the design, acquisition of data, analysis of data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

As an adviser of the journal, HKL Yuen was not involved in the peer review process. Other authors have disclosed no conflicts of interest.

This pictorial medicine received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

The patient was treated in accordance with the Declaration of Helsinki. The patient provided written informed consent for the treatment/procedures, and consent for publication.

1. Na JI, Kwon OS, Kim BJ, et al. Ethnic characteristics of eyelashes: a comparative analysis in Asian and Caucasian females. Br J Dermatol 2006;155:1170-6. Crossref

2. Colombe L, Michelet JF, Bernard BA. Prostanoid receptors in anagen human hair follicles. Exp Dermatol 2008;17:63- 72. Crossref

3. Dalal A, Sharma S, Kumar A, Sharma N. Eyelash trichomegaly: a rare presenting feature of systemic lupus erythematosus. Int J Trichology 2017;9:79-81. Crossref

4. Jeon SH, Ryu JS, Choi GS, et al. Erlotinib induced trichomegaly of the eyelashes. Tuberc Respir Dis (Seoul) 2013;74:37-40. Crossref

5. Chanprapaph K, Pongcharoen P, Vachiramon V. Cutaneous adverse events of epidermal growth factor receptor inhibitors: A retrospective review of 99 cases. Indian J Dermatol Venereol Leprol 2015;81:547. Crossref

6. Lacouture ME, Lai SE. The PRIDE (Papulopustules and/or paronychia, Regulatory abnormalities of hair growth, Itching, and Dryness due to Epidermal growth factor receptor inhibitors) syndrome. Br J Dermatol 2006;155:852-4. Crossref

In April 2019, a 22-year-old woman was admitted to Union Hospital, Hong Kong, with right loin pain and fever. She had developed acute cystitis symptoms 1 week prior to the admission and was prescribed a course of oral antibiotic. She had good past health with no history of urinary tract infection. On admission she had a temperature of 39°C. The abdomen was soft and non-tender. Laboratory tests revealed a normal white cell count of 6.09 × 10⁹/L and normal serum creatinine level of 54 μmol/L. The C-reactive protein level was elevated at 45.5 mg/L. Urine tests revealed a slightly turbid urine with elevated white blood cell count of 260 cells/µL. There was no significant growth on urine culture. An urgent contrast computed tomography scan revealed features suggestive of pyelonephritis at the lower pole of the right kidney (Fig 1). There was no obstructive urinary stone. In addition, the imaging demonstrated an atypical right pelvicalyceal system (Fig 2). A course of antibiotic was prescribed with good clinical response. Repeat urine microscopy was unremarkable 8 weeks after the initial presentation. Follow-up computed tomography scan confirmed resolution of right pyelonephritis but the unusual finding of the right pelvicalyceal system remained unchanged (Fig 3).

The radiological features were diagnostic of congenital megacalycosis. The anomaly is characterised by caliectasis with malformation. The classic triangular or conical shape of the renal calyces is replaced by a semilunar configuration. The pyramids of Malpighi are hypoplastic and the tip of each papilla is flat. The calyces have a rounded appearance with neither fornix nor papillae impressions. Polycalycosis is another feature of the condition and typically 20 to 25 calyces can be identified. The condition is differentiated from obstruction by the finding of a non-dilated renal pelvis, infundibulum, and ureter. The renal cortex was of normal thickness with good concentration of contrast medium in the distended calyces (Figs 2 and 3).

Congenital megacalycosis is a rare condition with approximately 100 cases reported in the literature. The anomaly is found predominantly in men and usually affects only one kidney. The exact pathogenesis remains unclear.1 2 3 The condition is usually asymptomatic and is detected during workup of urinary stone disease or urinary tract

infection in adults. On the contrary, reports of congenital megacalycosis in paediatric patients are on the rise with the increasing use of imaging in antenatal screening.4 Although urinary stasis in the distended calyces may predispose to infection and stone formation,1 2 renal function remains normal and neither anatomic nor functional deterioration occur over time.5 The benign nature suggests that megacalycosis should be considered a condition rather than a disease, and the term “megacalycose” has been suggested as an alternative term by some authors. Treatment should target complications only. Identification of the condition is important to avoid unnecessary investigation and intervention in a normally functioning kidney despite the inherent anatomic defect.2

Concept or design: CL Cho.
Acquisition of data: All authors.
Analysis or interpretation of data: All authors.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important intellectual content: All authors.

All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

The authors have disclosed no conflicts of interest.

This pictorial medicine paper received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

This study was conducted in accordance with the principles outlined in the Declaration of Helsinki. Verbal consent was obtained for the purpose of case study.

1. Puigvert A. Le megacalice. J Urol Nephrol 1964;70:321-6. Crossref

2. Kimche D, Lask D. Megacalycosis. Urology 1982;19:478-81. Crossref

3. Kalaitzis C, Patris E, Deligeorgiou E, et al. Radiological findings and the clinical importance of megacalycosis. Res Rep Urol 2015;7:153-5. Crossref

4. Kasap B, Kavukçu S, Soylu A, et al. Megacalycosis: report of two cases. Pediatr Nephrol 2005;20:828-30. Crossref

5. Redman JF, Neeb AD. Congenital megacalycosis: a forgotten diagnosis? Urology 2005;65:384-5. Crossref

A 44-year-old woman presented to our anaphylaxis clinic with first episode of anaphylaxis. She had no known prior food or drug allergies. She was previously prescribed esomeprazole 20 mg daily as required for dyspepsia by her private physician, but took it only very occasionally. Two months previously she took one tablet of esomeprazole (20 mg) and one of paracetamol (500 mg) together with a slice of plain bread for abdominal discomfort and influenza-like symptoms. Within 10 minutes, she experienced generalised pruritus and collapsed at home. She awoke after hitting the floor and telephoned for an ambulance. She was treated with intramuscular adrenaline in the ambulance because systolic blood pressure had fallen to <80 mm Hg. Initial investigations revealed a significant rise in acute tryptase (12.3 ng/mL) with a normal baseline level (2.1 ng/mL). Initially wheat or wheat-dependent cofactor augmented anaphylaxis was suspected. She was advised to avoid wheat, cyclooxygenase inhibitors, and proton pump inhibitors (PPI) until review.

Results for specific immunoglobulin E to wheat and omega-5-gliadin were negative. Skin prick test (SPT) to wheat solution (Inmunotek, Madrid, Spain) and prick-to-prick with the index bread slice was also negative. Skin prick test and intradermal tests (IDT) to paracetamol (both 100 mg/mL, GlaxoSmithKline, London, United Kingdom) were also negative. The patient tolerated an oral challenge with 500 mg of paracetamol together with a slice of the same index bread with no adverse reaction.

The SPT (8 mg/mL) and IDT (8 mg/mL, 0.8 mg/mL and 0.08 mg/mL; AstraZeneca, Bedfordshire, United Kingdom) were performed and are shown in the Figure. Skin prick test to histamine (positive control) and normal saline (negative control) was positive at 5 mm and negative at 0 mm, respectively. Skin prick test to esomeprazole was borderline positive with a 3-mm wheal and flare. Intradermal test to esomeprazole was positive at concentrations of 8 mg/mL, 0.8 mg/mL and 0.08 mg/mL; with 18-mm, 8-mm and 3-mm wheal expansion, respectively. The SPT and IDT with 8 mg/mL and 0.8 mg/mL were negative in a healthy control (the author) as shown in the Figure. To assess for potential cross-reactivity, SPT (4 mg/mL) and IDT (4 mg/mL and 0.4 mg/mL) to pantoprazole were also performed and are also shown in the Figure. The SPT was negative, but IDT was positive with 4 mg/mL and 0.4 mg/mL dilutions with 7-mm and 4-mm wheal expansion, respectively.

She was diagnosed with severe type I hypersensitivity to esomeprazole with cross-sensitisation to pantoprazole. Drug provocoation testing was not indicated in view of the compatible clinical history, strongly positive skin tests, and high risk of anaphylaxis. The patient declined testing with other PPI and was advised to avoid the entire class until further workup. She was prescribed famotidine 20 mg twice a day for her dyspepsia with no adverse effects.

This is the first reported case in Hong Kong of PPI anaphylaxis and demonstrates the utility of skin testing to assess potential cross-reactivity. Although relatively uncommon, reports of hypersensitivity to PPI are increasing, in parallel with their increasing use worldwide. The majority of hypersensitivity reactions appear to be of the immediate type.1 Previous exposure to esomeprazole may have been initial sensitising events. Despite common misconception, clinicians should bear in mind that prior tolerance of a certain drug does not preclude it as a future cause of drug allergy. Although patterns of cross-reactivity among various PPIs have been reported, these remain controversial and a thorough allergological workup should be performed for every patient.2 Clinicians are reminded to be vigilant of this uncommon cause of anaphylaxis and beware of potential cross-reactivity. The SPT and IDT have high specificity, but patients with suspected PPI hypersensitivity and negative skin tests should undergo drug provocation tests to confidently exclude this important diagnosis.3

The author contributed to the concept or design, acquisition of data, analysis or interpretation of data, drafting of the manuscript, and critical revision for important intellectual content. The author had full access to the data, contributed to the study, approved the final version for publication, and takes responsibility for its accuracy and integrity.

The author has disclosed no conflicts of interest.

This pictorial medicine paper received no specific grant from any funding agency in the public, commercial, or not-forprofit sectors.

The patient consented to this publication.

1. Otani IM, Banerji A. Immediate and delayed hypersensitivity reactions to proton pump inhibitors: evaluation and management. Curr Allergy Asthma Rep 2016;16:17. Crossref

2. Tourillon C, Mahe J, Baron A, et al. Immediate-type hypersensitivity cross-reactions to proton pump inhibitors: a descriptive study of data from the French National Pharmacovigilance Database. Int Arch Allergy Immunol 2019;178:159-66. Crossref

3. Kepil Özdemir S, Yilmaz I, Aydin Ö, et al. Immediate-type hypersensitivity reactions to proton pump inhibitors: usefulness of skin tests in the diagnosis and assessment of cross-reactivity. Allergy 2013;68:1008-14. Crossref

Schwannoma is a rare tumour in the liver. It is likely to arise from the hepatobiliary nerves among the hepatic plexus in the liver hilum as well as interlobular connective tissues and hepatic arteries. To the best of our knowledge, no prior publications have reported cases in Hong Kong.

We report the case of a 64-year-old man with a history of nasopharyngeal carcinoma and colon carcinoma and a new liver lesion detected on follow-up imaging for surveillance in 2018 following detection of a slightly elevated serum MEDICINEcarcinoembryonic antigen level (4.7 μg/L). Alpha fetoprotein level was within the normal range (3.9 μg/L). Liver function tests were normal and he was asymptomatic with no history of neurofibromatosis.

Triphasic contrast computed tomography (CT) of the liver revealed a 5.2-cm ovoid hypodense lesion with heterogeneous enhancement in the caudate lobe of the liver (Fig 1). No washout of contrast was evident in the portal venous or delayed phases. Fluorodeoxyglucose-18 positron emission tomography–CT showed a moderately hypermetabolic lesion at the caudate lobe with a maximum standardised update value of 5.8 (Fig 2).

Surgical resection of the lesion was performed (Fig 3). Pathology showed a schwannoma and degenerative changes. Histological examination revealed an encapsulated tumour consisting of highly ordered Antoni type A and B areas (Fig 4). Immunohistochemical analysis showed the tumour cells to be diffusely positive for S100, consistent with neural differentiation (Fig 4). HerPar1, a mitochondrial antigen of hepatocytes, was negative. The CD34, a cell surface glycoprotein that is positive in gastrointestinal stromal tumour, was also negative.

Schwannoma is most commonly found in the limbs and the head and neck region. A fifth of cases shows association with neurofibromatosis type 1. The mediastinum and retroperitoneum are other possible sites. It is uncommon in the gastrointestinal tract and extremely rare in the liver.1 It was first reported in 1978 by Pereira et al.2 A literature search through PubMed and MEDLINE revealed 32 reported cases. No cases have been published in Hong Kong.

The origin of hepatic schwannoma is the hepatobiliary nerves among the hepatic plexus in the liver hilum as well as interlobular connective tissues and the hepatic arteries.1 3 They are usually well-encapsulated and grow very slowly, usually smaller than 5 cm at the time of diagnosis. Larger schwannomas may undergo secondary degeneration with consequent pseudocystic regression, haemorrhage, and calcification. Malignant transformation is very rare.3

Pathologically, a schwannoma is an encapsulated tumour that arises within the nerve sheaths. It consists of a highly ordered cellular component (Antoni type A area) characterised by spindle cells with twisted nuclei arranged in short bundles, and a hypocellular area in a loose myxoid stroma (Antoni type B area) that comprises a loose meshwork of gelatinous and microcystic tissue.4

On imaging, hepatic schwannoma is usually well circumscribed with various signal characteristics, depending on the distribution of Antoni A and Antoni B areas.1 It is commonly of low density with heterogeneous enhancement on CT, hypointense on T1-weighted, and hyperintense on T2-weighted magnetic resonance imaging.5 There have also been reports of malignant tumours but there are no distinct radiological features that differentiate them from benign tumours.3 A hepatic schwannoma may be fluorodeoxyglucose-avid depending on inflammatory activity and cellularity. Fluorodeoxyglucose-18 positron emission tomography–CT alone may enable differentiation of a schwannoma from malignant lesions of the liver.1

Hepatic schwannoma is an extremely rare tumour and preoperative diagnosis with imaging is challenging. Biopsy or surgical resection is usually required for definitive diagnosis.

Concept or design: All authors.
Acquisition of data: HL Tsui and CH Lau.
Analysis or interpretation of data: HL Tsui, SM Yu, and CH Lau.
Drafting of the manuscript: HL Tsui, SM Yu, and CH Lau.
Critical revision of the manuscript for important intellectual content: All authors.

All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

All authors have disclosed no conflicts of interest.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

This study is approved by the cluster Research Ethics Committee (Ref KC/KE-19-0247/ER-3). Written patient consent was also obtained.

1. Hayashi M, Takeshita A, Yamamoto K, Tanigawa N. Primary hepatic benign schwannoma. World J Gastrointest Surg 2012;4:73-8. Crossref

2. Pereira Filho RA, Souza SA, Oliveira Filho JA. Primary neurilemmal tumour of the liver: case report. Arq Gastroenterol 1978;15:136-8.

3. Ozkan EE, Guldur M, Uzunkoy A. A case report of benign schwannoma of the liver. Intern Med 2010;49:1533-6. Crossref

4. Wan DL, Zhai ZL, Ren KW, Yang YC, Lin SZ, Zheng SS. Hepatic schwannoma: a case report and an updated 40-year review of the literature yielding 30 cases. Mol Clin Oncol 2016;4:959-64. Crossref

5. Yamamoto M, Hasegawa K, Arita J, et al. Primary hepatic schwannoma: a case report. Int J Surg Case Rep 2016;29:146-50. Crossref