Ocular surface squamous neoplasia in Zambia

In this blog one may find lots of pictures of OSSN. Finally we got some science for that!

Clinical and Pathologic Presentation of Primary Ocular Surface Tumors among Zambians
Peter Julius et al. Ocul Oncol Pathol. 2021 Mar;7(2):108-120.
doi: 10.1159/000511610. Epub 2021 Jan 21.

Peter Julius 1 , Stepfanie N Siyumbwa 1 , Phyllis Moonga 2 , Fred Maate 1 , Trevor Kaile 1 , Guobin Kang 3 , John T West 4 , Charles Wood 3 , Peter C Angeletti 3

1 Department of Pathology and Microbiology, School of Medicine, Lusaka, Zambia.
2 University Teaching Hospital, Eye Hospital, Lusaka, Zambia.
3 Nebraska Center for Virology and the School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
4 Nebraska Center for Virology and the Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.

PMID: 33869164
PMCID: PMC8024974 (available on 2022-03-01)
DOI: 10.1159/000511610

Aim: This study aimed to characterize the clinical and pathologic presentation of ocular surface tumors (OSTs) and to more precisely differentiate the grades of ocular surface squamous neoplasia (OSSN) and benign lesions among Zambians.

Methods: Two-hundred sixty-five Zambian patients presenting with ocular surface growths, suspicious for OSSN, were recruited between November 2017 and November 2019 to a cross-sectional study to investigate their lesions. Sociodemographic data were collected, HIV infection status and vision tests were performed, and lesions were measured and documented. Lesions >2 mm in diameter were excised and sent for pathology analysis. In addition to the biopsies, tears, blood, and buccal swabs were collected. CD4+ T-cell counts were measured by flow cytometry. Lesions were classified according to the WHO guidelines. χ2 and bivariate correlations were used to analyze variable associations and strengths with phi/Cramer’s V and correlation coefficients, respectively. Binary logistics was used to adjust for covariance.

Results: In this study, 68.3% of the participants were found to be HIV positive. The most frequent diagnoses were invasive OSSN (45.3%), preinvasive OSSN (29.1%), and pterygium (22.6%). Invasive OSSN comprised keratinizing squamous cell carcinoma (SCC) (87.5%), basaloid SCC (3.3%), and spindle cell carcinoma (3.3%). Unusual carcinomas, not described previously, included hybrid SCC (5.0%) and acantholytic SCC (0.8%). Invasive OSSN had advanced tumor (T3/T4) staging (93.3%) at diagnosis. Lymphadenopathy was rare (2.3%), and metastasis was absent. Patients were mostly female (59.2%). Median age was 36 (interquartile ranges 33-41) years (ranges 18-81). Patients with invasive OSSN were more likely to present with pain (p = 0.007), redness (p = 0.034), excessive tearing (p = 0.0001), discharge (p = 0.011), bleeding (p = 0.007), reduced vision (p = 0.0001), fungating lesion (p = 0.001), and blindness (p = 0.005); location at temporal limbus (p = 0.0001), inferior limbus (p = 0.0001), or circumlimbal (p = 0.001); and extension to cornea (p = 0.006) and forniceal palpebral conjunctiva (p = 0.001). Invasive OSSN was associated with any smoking habit and alcohol consumption (p = 0.04 and 0.03, respectively). HIV positivity was strongly associated with OSSN (74.6% OSSN vs. 49.3% benign lesions; p = 0.0001; phi: 0.237 [p = 0.0001]).

Conclusion: OSTs are very common in Zambia and are strongly associated with HIV coinfection. Patients with OSSN were more likely to be HIV positive than those with pterygia. Despite the commonality of OSTs in sub-Saharan Africa, these cancers have historically been poorly characterized

Eye precancerous lesions mimic benign pyogenic granuloma

Not all pyogenic granulomas are equally safe. Some of them may comprise an elements of ocular surface squamous neoplasia, OSSN (conjunctival intraepithelial neoplasia, CIN). The paper Herwig-Carl MC, Grossniklaus HE, Müller PL, et al. Br J Ophthalmol Epub. doi:10.1136/ bjophthalmol-2018-312960 highlighted 9 such cases.

OSSN is extremely common in the areas with widespread HIV-prevalence. Human papilloma virus is responsible for this, as a typical opportunistic infection. Knowledge of the potential of OSSN to mimic pterygia and pyogenic granulomas is crucial, especially for the mid level ophthalmic personnel, as they are the primary surgeons for these conditions in many areas.

Pyogenic Granuloma Associated With Conjunctival Epithelial Neoplasia: Report of Nine Cases

Aims: To systematically describe the clinical and histopathological features of a case series of conjunctival carcinomatous lesions underlying as-and also masquerading-pyogenic granuloma.

Methods: Nine cases of conjunctival carcinomatous lesions underlying a pyogenic granuloma (which were clinically predominant) were retrospectively identified. Patients’ records were analysed for demographic data, clinical appearance and the postoperative course. Formalin-fixed paraffin-embedded specimens were routinely processed and stained with H&E and periodic acid-Schiff. Immunohistochemical stains for cytokeratin were performed in selected cases.

Results: All nine tumours were located in the conjunctiva (bulbar, tarsal, limbal conjunctiva) of patients between 44 and 80 years. The lesions exhibited clinical features of pyogenic granuloma which dominated the clinical appearance. Additional features comprised a papillomatous appearance of the adjacent conjunctiva, a more whitish aspect of the lesion and a history of squamous cell carcinoma (SCC) respectively surgery for other entities. Histopathological analysis revealed a carcinomatous lesion (conjunctival intraepithelial neoplasia or SCC) at the base of a classic pyogenic granuloma in all nine cases. Surgical removal (R0 resection) was performed. Three cases received adjuvant mitomycin C or interferon α2b treatment. Two lesions locally recurred within 2 years after initial presentation.

Conclusion: Carcinomatous lesions may be accompanied by a pyogenic granuloma which may dominate the clinical pictures. As the tumour is usually located at the base of the lesion, a complete surgical excision followed by histopathological analysis is mandatory for each lesion appearing as conjunctival pyogenic granuloma.

Keywords: conjunctival intraepithelial neoplasia; histology; pyogenic granuloma; squamous cell carcinoma; tumour.

One more squamous cell carcinoma of conjunctiva

In EnglishEN: A case of September 2016. Squamous cell carcinoma of conjunctiva (SCC). A young male patient had recently found out his positive HIV status. This SCC is yet presumably non-invasive to the sclera. This tumor was unresponsive to three on-off cycles of 5-fluorouracyl (5-FU) eye drops. The risk of recurrence after simple excision with antimetabolites is relatively high.

Of interest: the eye removal (enucleation) was not indicated. The tumor was excised (no-touch technique) with application of 5-FU. Superficial sclerectomy is also a good additional measure to avoid recurrence in cases suggestive of sclera invasion. However in this case an additional cryotherapy was planned, but failed due to machine failure. The patient was referred for the cryo into the capital city.

Also of interest: it is not wise to cover the resultant defect with conjunctiva, there is a risk of recurrence, which we can thus miss. Nevertheless, the option of amniotic membrane coverage is described in the literature, and I witnessed this technique in the USA.

The chances for exenteration in future in African setup are relatively high! The patients with the eyes, which can see 1,0, rarely allow eye amputation, thus receiving often a super-huge tumors, amenable only to exenteration!

A similar case was already presented in the Atlas (see the link below).

in Russian / по-русскиRU: Случай от сентября 2016 г. Плоскоклеточный рак конъюнктивы. Молодой пациент, недавно узнавший о своём положительном статусе по ВИЧ. Плоскоклеточный рак, предположительно пока без склеральной инвазии. Этой опухоли не помогли три цикла химиоредукции с 5-фторурацилом. Крайне высокие риски на рецидив, даже с применением антиметаболитов.

Ложе после удаления опухоли конъюнктивой не покрывается: это чревато пропуском рецидивов. Тем не менее, в США я наблюдал покрытие ложа амнионом. Такое описано в литературе и часто практикуется.

Тактика на момент лечения не включала в себя удаление глаза! Эта опухоль была иссечена. Недостаточно глубоко.. Планировал крио, но вышли проблемы с газом. При отсутствии крио шансы на повторный рост были очень высокие: такие опухоли требуют помимо аппликации антиметаболитов и некоторый объём склерэктомии (чего в данном случае не было сделано). Пациент был направлен на криолечение в столицу. Шансы на то, что закончиться это могло, тем не менее, не энуклеацией – экзентерацией, – относительно немалые, по простой причине: пациенты, особенно с рецидивами, и особенно со зрением единица – не готовы к удалению глаза, запуская рост опухоли до крайних размеров.

Аналогичный случай с похожей опухолью уже представлен в атласе: Conjunctival Squamous Cell Carcinoma.

Advanced OSSN

Advanced OSSN

Advanced OSSN

Advanced OSSN

Advanced OSSN ultrasound biomicroscopy

Invasive squamous cell carcinoma of conjunctiva looks like melanoma

In EnglishEN: Case of May 2016: patient presented with this brown elevated slowly-growing mass. Differential in our setup will always include OSSN. We know that conjunctival melanoma, uveal melanoma and skin melanoma are all quite rare in dark skinned people, though we consider it for differential as well (PMID 18191091). Histopathology confirmed invasive squamous cell carcinoma. It is hardly probable for OSSN to be black in white people. Nevertheless it is quite common in blacks.

Ideal treatment: wide excision with no-touch technique, followed by antimetabolites (5-FU/MMC) or cryotherapy. Lamellar sclerectomy is indicated when invasion is suspected. This case was managed without cryo. The technique for cryo is good described here:

Cryoprobe was placed on the lifted conjunctival margin for 3 seconds and then allowed to thaw. • A subsequent 3-second application would be applied adjacent to and slightly overlapping the prior application. Upon reaching the limbal margin, the cryoprobe was placed such that it would freeze the limbus and about 0.5mm of cornea.


in Russian / по-русскиRU: Инвазивный плоскоклеточный рак: чёрный маскарад. Случай от мая 2016 г.
Редкий случай чёрной поверхностной неоплазии глаза. В дифференциальный диагноз входила меланома, однако гистология подтвердила инвазивный плоскоклеточный рак. Довольно нетипичная пигментация, даже для чернокожих. Известно, что поверхностная неоплазия у белых людей практически не бывает пигментированной. В то же время, это не редкость среди людей с тёмной кожей. Полезный факт – всё глазные варианты меланомы – меланома кожи, сосудистой оболочки глаза и конъюнктивы глаза – встречаются значительно реже у чернокожих людей. Средняя по больнице заболеваемость конъюнктивальной меланомой – 0,012 на 100 тыс. населения (PMID 9763137). Но у чернокожих людей частота меланомы минимум в 3-4 раза меньше, чем у белых (PMID 18191091).

Invasive pigmented squamous cell carcinoma of conjunctiva. DDx: melanoma.

Invasive pigmented squamous cell carcinoma of conjunctiva. DDx: melanoma.