Enabling healthcare providers in resource-limited settings to submit skin biopsy specimens in difficult clinical cases that have been submitted for teledermatology evaluation has allowed for definitive diagnosis and appropriate management of patients with serious dermatological conditions. In countries where pathology services are limited or unavailable, the transport of fixed tissue to an experienced pathology laboratory may be a feasible option for histological analysis of skin biopsies. In the biopsies submitted for analysis through the African Teledermatology Project, the clinical diagnosis was confirmed by histological examination in 58% of cases and provided useful information in the management of patients with both malignant and benign conditions. Over half of cases confirmed malignancies, of which 81% (13/16) represent HIV-associated KS in patients with very low CD4 counts. Prior to initiating the scarcely available and costly chemotherapy in resource-limited settings, histological diagnosis is imperative. In the one case of tumoral stage cutaneous T-cell lymphoma, the confirmation of a malignant process and exclusion of infectious etiology allowed for targeted therapy and avoidance of unnecessary complications. Histological confirmation of benign diagnoses is equally important: confirmation of multiple steatocystomas on the chest of a young African man permitted reassurance and prevented the proposed surgical excision and subsequent deformation of the entire chest wall. Clinicopathological correlation and histological confirmation allow for the delivery of high-quality health care and avoidance of empiric treatments that may lead to worsening of the condition and unnecessary costs. In order to optimize the use of resources, clinicopathological correlation should be reserved for the most difficult cases with management implications.
KS diagnoses deserve special attention given the prevalence of HIV infection in patients presenting to dermatology clinics in sub-Saharan Africa. The HIV status of 50% of the 345 consultation cases submitted through the African Teledermatology Project is known, and of these 174 cases, 71.8% were HIV-infected and/or had HIV/AIDS-associated skin conditions.2
This prevalence explains clinicians' high suspicion for KS diagnoses in biopsy specimens and the common request for special stains to confirm the suspected diagnosis. Prior studies have demonstrated up to 90–100% sensitivity and 100% specificity for monoclonal antibodies to HHV-8 ().9–11
Histology demonstrating KS, with an atypical spindle cell proliferation with extravasated red blood cells (left) and positive nuclear HHV-8 staining (right). (Original power × 400)
Over half of cases lacking clinicopathological correlation (11 out of 21) involved clinically suspected or microscopically confirmed KS. In 10 cases, KS was suspected clinically but revealed different disease processes histologically. Three of these 10 cases represent lichenoid tissue reactions with prominent pigment incontinence on histology. Clinically these cases represent flat hyper-pigmented patches and thin plaques, which mimic early patch stage KS. The case of vasculitis by histology had a clinical history highly suggestive of KS; the clinical lesion presented as a nodule on the lower extremity of an HIV+ patient with a CD4 count of 200. Three cases suspected of KS clinically were confirmed as infections and, in these cases, appropriate antimicrobial therapy resulted in clinical improvement.
In only one histologically confirmed case of KS was the diagnosis not clinically suspected or included in the differential diagnosis and clinical history. This particular single lesion presented on the chin of a child and initially improved on oral antibiotic therapy but recurred as an ulcerated nodule. In another case, the clinician had a low suspicion for KS based upon the patient's CD4 count of 950 (). KS was listed on the differential diagnosis and was confirmed by histology and HHV-8+ staining. These cases underscore the important role of histology in definitively diagnosing a serious dermatological disease in immunocompromised patients in whom the differential diagnosis is broad and the management is complex.
Patient with a CD4 count of 950 with nodule ultimately diagnosed as KS
There are limitations to this study. First, the retrospective nature and inclusion criteria permit us only to look at cases submitted in consultation and therefore may not represent the true population burden of disease in the local areas from which they derive. Second, scarcity of resources in Africa, namely biopsy kits and formalin, create an inherent selection bias for only the most challenging cases that require histological assistance for diagnosis. Selection of only the most difficult cases might explain, in part, the relatively low rate of clinicopathological correlation. Furthermore, clinicopathological correlation requires the presence of accurate clinical information, which often was not included with the case. Third, not all biopsy specimens resulted in a clearly defined histological diagnosis. The transportation time of the biopsies from Africa to the USA was on average less than one week; however, in rare cases the time from obtaining the specimen to arrival in the processing laboratory exceeded one month. In transport, one of the non-diagnostic cases was lost for weeks and arrived dry without formalin in the biopsy cup. Finally, this study does not evaluate the impact of diagnostic data derived from histological examination. Clinicians submitting specimens are responsible for identifying and managing the patients in question, and due to the method by which specimens are sent, there are no structured mechanisms in place to inform dermatopathologists of the ultimate patient outcome. Further investigation and research in these areas is required.
This study highlights the significant contribution dermatopathology services can provide in the diagnosis and treatment of skin disease in the developing world. Efforts to expand dermatological care to rural parts of the developing world will rely heavily on partnerships between local clinics and urban academic medical centers, as well as creative implementation of technology and reappropriation of resources. Store and forward teledermatology can be used to provide dermatological care and education in settings where no specialists exist. Histological examination of skin biopsy specimens in difficult clinical cases can assist in definitive diagnosis. In countries where there are no histological services, one solution is the shipment of wet tissue to experienced laboratories. In order to ship the tissue in a cost-effective manner in resource-limited settings, innovative specimen containers, such as old medicine vials, are often used to hold formalin-fixed tissue (). The obvious logistic limitations to this practice are the time to send specimens and cost of shipment.
Creative solutions to resource scarcity include the reuse of empty medicine vials as histology specimen containers
We have examined other possibilities for histological evaluation of skin specimens, including wet tissue processing at local sites and the use of teledermatopathology. Eighty-six percent of Sub-Saharan African countries report the presence of histology or lab processing service; however, the extensive time to receive results is often prohibitive.4
Digital images of scanned slides could be reviewed in a store-forward fashion over the existing web-based African Teledermatology Project in a manner similar to that currently used for clinical images; however, this would require local tissue processing, slide scanning technology, and internet with sufficient bandwidth. Alternatively, a robotic microscope can be installed at the local site, and slides may be loaded to be reviewed remotely in real time by a remote expert. A robotic microscope has been established in Botswana in conjunction with the University of California Los Angeles and the University of Pennsylvania and is currently in use by one author (CLK) in the USA. This method, however, also relies on the ability to process tissue locally as well as a local pathologist with whom to partner and collaborate.
These exciting technologies offer several possible solutions to increasing access to dermatopathology services and expert physician consultation as an adjunct to clinical teledermatology. Numerous modalities need to be evaluated and researched to develop the best strategies to increase access to care in the developing world and allow for clinicopathological correlation. Dermatopathology solutions also will need to be tailored to specific sites, as their capabilities and access to resources vary greatly.