Darier disease: Histopathology revisited.

ABSTRACT: Darier disease (DD) is a rare genodermatosis. Literature on this topic is overwhelmingly dominated by case reports with rare clinical presentations, which have mentioned the histopathologic features briefly. The aim of this study was to document the histopathology of DD. Skin biopsies diagnosed as Darier disease based on clinicopathologic correlation over 12 years were reviewed for various epidermal and dermal features. There were 16 patients included, who most commonly presented in the third decade, with slight female predilection. The most common clinical presentation was hyperpigmented, hyperkeratotic, papules and plaques (91%), with 69% affecting the trunk. In addition to the classic suprabasal acantholytic clefts, we noted some unusual features: absence of parakeratosis (19%), a cornoid lamella-like pattern (62%), follicular acantholysis (13%) and multiple foci of involvement within a single biopsy (63%). Features such as the presence of dyskeratotic cells and minimal dermal lymphocytic infiltrates were concordant with previous literature. The limitation of this study was the small sample size. To conclude, pathologists must be aware of the variations in histopathology of Darier's disease, especially when challenged with atypical clinical presentations. The Darier-like pattern is met within several acantholytic diseases, and clinicopathologic correlation has the last word in arriving at a diagnosis.

Vulvar Lichenoid Dermatoses With Emphasis on the Distinction Between Lichen Sclerosus and Lichen Planus: A 10-Year Study.

OBJECTIVES: Lichen planus (LP) and lichen sclerosus (LS) are the most common vulvar lichenoid dermatoses. The diagnostic challenges are due to site-specific variation in microscopic appearance and small-sized biopsies. Authentication of diagnostic criteria to distinguish LS and LP to uncover any resemblance or divergence in presentation of these conditions is attempted. METHODS: Cases of vulvar LP and LS diagnosed between January 2012 to December 2022 were included. The clinical details included age, presenting symptoms, examination findings, and other organ involvement. Histopathological analysis of epidermal, dermal, and adnexal findings was done. RESULTS: There were 28 cases of vulvar LP and 72 cases of LS, with a median age of 51 and 60 years, respectively. Depigmentation and atrophy were the major clinical features in LS, whereas ulcers/erosions and erythema were more prevalent in LP with a significantly higher incidence of oral involvement. The most diagnostic feature in LS was diffuse dermal sclerosis (76.8%) and interstitial pattern of inflammation (81.4%), whereas the characteristic features in LP cases was a lichenoid pattern of inflammation (85.7%), necrotic keratinocytes, and lymphocytic exocytosis. In 44.4% of LS, unconventional features like compact orthokeratosis, parakeratosis, thickened/wedge-shaped hypergranulosis, and sawtooth rete pegs were noted. Lichen sclerosus with lichenoid inflammation (21.4%) mimicked LP, from which it was distinguished by presence of thickened or diminished granular layer with basal melanin absence (60%) and dermal homogenization (80%). CONCLUSION: Although the classical, well-established variant of LS poses no diagnostic difficulty, the unconventional variant may mimic LP. Identification of the subtle histological clues demonstrated in this study can help to arrive at the correct diagnosis.

The master of masquerade: A case series of unusual presentations of cutaneous tuberculosis in the immunocompromised host.

Cutaneous tuberculosis is known for its varied presentations, especially in the setting of immunosuppression. Clinical manifestations can be modified by the site of involvement as well as the type of cutaneous tuberculosis in a particular patient. Although cutaneous tuberculosis only accounts for a small percentage (1-2%) of extrapulmonary cases, it is encountered fairly frequently in dermatology practice in an endemic country like India. These cases are being presented to highlight unusual presentations of well-known forms of cutaneous TB (TB gumma and erythema induratum of Bazin) and rare morphologies (panniculitis) in immunosuppressed individuals, thereby emphasizing the need for the dermatologist in a TB-endemic country to be constantly vigilant.

MIC and Upper Limit of Wild-Type Distribution for 13 Antifungal Agents against a Trichophyton mentagrophytes-Trichophyton interdigitale Complex of Indian Origin.

Dermatophytosis due to the Trichophyton mentagrophytes-Trichophyton interdigitale complex is being increasingly reported across India. Reports of therapeutic failure have surfaced recently, but there are no clinical break points (CBP) or epidemiological cutoffs (ECVs) available to guide the treatment of dermatophytosis. In this study, a total of 498 isolates of the T. mentagrophytes-interdigitale complex were collected from six medical centers over a period of five years (2014 to 2018). Antifungal susceptibility testing of the isolates was carried out for itraconazole, fluconazole, ketoconazole, voriconazole, luliconazole, sertaconazole, miconazole, clotrimazole, terbinafine, amorolfine, naftifine, ciclopirox olamine, and griseofulvin. The MICs (in mg/liter) comprising >95% of the modeled populations were as follows: 0.06 for miconazole, luliconazole, and amorolfine; 0.25 for voriconazole; 0.5 for itraconazole, ketoconazole, and ciclopirox olamine; 1 for clotrimazole and sertaconazole; 8 for terbinafine; 16 for naftifine; 32 for fluconazole; and 64 for griseofulvin. A high percentage of isolates above the upper limit of the wild-type MIC (UL-WT) were observed for miconazole (29%), luliconazole (13.9%), terbinafine (11.4%), naftifine (5.2%), and voriconazole (4.8%), while they were low for itraconazole (0.2%). Since the MICs of itraconazole were low against the T. mentagrophytes-interdigitale complex, this could be considered the choice of first-line treatment. The F397L mutation in the squalene epoxidase (SE) gene was observed in 77.1% of isolates with a terbinafine MIC of ≥1 mg/liter, but no mutation was detected in isolates with a terbinafine MIC of <1 mg/liter. In the absence of CBPs, evaluation of the UL-WT may be beneficial for managing dermatophytosis and monitoring the emergence of isolates with reduced susceptibility.

"Joining the Spots in Adults and Young Tots": A Clinicopathological Study of Henoch-Schönlein Purpura (IgA Vasculitis).

INTRODUCTION: Henoch-Schönlein Purpura (HSP; IgA vasculitis), the most common vasculitis of childhood, has a wide spectrum of clinical manifestations ranging from palpable purpura with abdominal pain and arthritis to the more morbid renal involvement. AIMS AND OBJECTIVES: To study and correlate the clinical presentation, laboratory values, skin and renal histopathology and immunofluoroscence findings in HSP. MATERIAL AND METHODS: A total of 44 cases of HSP from March 2011 to February 2014 were studied for the above features along with their clinical outcomes. RESULTS: The mean age of the patients at presentation was 28.4 years (range 4.5-69 years) with 26.2% being children younger than 15 years. Purpura at presentation was seen in all with 77.1% cases exhibiting extracutaneous involvement. Skin biopsy revealed leukocytoclastic vasculitis in all cases, dominant IgA deposition in the papillary dermal vessels in 43 cases (97.7%), associated C3 in 10 cases (23.3%), and full-house positivity in 1 case. One case without skin immunofluorescence had renal mesangial IgA deposits. Nine cases (20.9%) with an average age of 39 years had renal symptoms and displayed varied histology from focal mesangioproliferative glomerulonephritis to crescentic. All of them had dominant mesangial IgA deposits, majority falling into International Study of Kidney Disease in Children (ISKDC) class IIIb. Peritubular capillaritis was noted in 3 cases. Two patients (4.5%) progressed to end stage renal disease, one of whom had cellular crescents at presentation. CONCLUSIONS: HSP was seen both in children and adults. Renal involvement was seen in 20.9% cases, all older than 14 years, and 66.7% with extracutaneous manifestations. The outcome in this series was favorable in 96% cases.

Papulonecrotic tuberculid-clinicopathologic and molecular features of 12 Indian patients.

BACKGROUND: Papulonecrotic tuberculid (PNT) is said to be a hypersensitivity reaction to M. tuberculosis. Some reports indicate that organisms are demonstrable by polymerase chain reaction (PCR). METHODS: We describe 12 patients with PNT over 6 years. We reviewed the histopathologic features, clinical data and follow-up. PCR for M. tuberculosis DNA was done in all cases. RESULTS: There were 7 men and 5 women. The ages ranged from 3-58 years. Upper limbs were commonly involved (8 cases). All patients had multiple papulonodular lesions, 5 showed ulceration and scarring. Mantoux test was strongly positive in all. Seven patients had systemic tuberculosis. On microscopy, necrosis was seen in 11 cases, varying from minimal to extensive. Epithelioid granulomas were common, except for 1 case with palisading and interstitial patterns. The infiltrate showed mostly lymphocytes, while 3 cases showed eosinophils. Vasculitis was seen in 8 cases. Two cases had dermal mucin, one also with interface dermatitis. This patient had concurrent LE. Mycobacterial DNA was detectable by PCR in 3 cases. Seven patients showed improvement/resolution of lesions on treatment. CONCLUSIONS: PNT is a rare disease. A positive PCR reiterates the question whether these are "tuberculids". PNT may be better classified as true cutaneous tuberculosis and patients screened for systemic disease.

Histopathology of scarring alopecia in Indian patients.

OBJECTIVES: Diagnosis of scarring alopecias (SAs) are challenging, especially when lesions late in the process of development are met with. There is a paucity of literature that profiles the role of histopathology in unscrambling this puzzle, especially in Indian patients. Our aim is to review the histological features of SA in Indian patients and attempt to assign a specific diagnosis. MATERIALS AND METHODS: We reviewed 37 cases of SA from 2005 to 2009. Sections were assessed for various histological parameters. RESULTS: There were 18 of 37 cases (49%) of lupus erythematosus, 15 of 37 (41%) lichen planopilaris (LPP), 1 folliculitis, and 3 alopecia areata. The important findings in lupus erythematosus are epidermal atrophy, papillary dermal fibrosis, mucin, peribulbar inflammation, and haphazard spacing of scars. LPP shows an essentially normal epidermis, peri-infundibular infiltrate, and even spacing of scars. Twelve cases had total absence of follicles and yet could be classified based on the connective tissue changes. Alcian blue-periodic acid-Schiff stain highlighted follicular remnants within scars in 9 cases. Three cases of alopecia areata demonstrated peribulbar inflammation, evenly spaced scars, and remnants of catagenic basement membrane. Cases termed as "pseudopelade" clinically were predominantly LPP on histology. CONCLUSIONS: Histopathology is a dependable tool in identifying the underlying cause in SA. Even in cases that show a complete loss of follicles, it is possible to suggest the etiology based on epidermal and connective tissue changes.

Follicular mycosis fungoides - A report of four Indian cases.

BACKGROUND: Follicular Mycosis Fungoides (FMF) is an under-recognized disease in India. Its clinical mimics include Hansen's disease and Sarcoidosis. AIMS: To describe the clinical and pathological features of FMF. MATERIALS AND METHODS: All cases of FMF between January and December 2007 were retrieved. Cases of conventional epidermotropic MF with a minor follicular component were excluded. Slides were reviewed by two observers. The following criteria were assessed: degree and density of folliculotropism of lymphocytes, location of folliculotropism (infundibular / isthmic / bulbar), follicular mucin, eosinophils, granulomas, and conventional epidermotropism. Each feature was assigned a semi-quantitative grade. RESULTS: There were four cases of FMF, with an equal gender distribution and a mean age of 17.5 years. All lesions were on the face. They presented as: hypopigmented patches (2) and erythematous plaques (2). Alopecia was seen in two cases. The clinical diagnosis was Hansen's disease in all four, with a differential of Alopecia mucinosa / Sarcoidosis in two cases.The histological features seen were: disproportionate folliculotropism, lymphocyte tagging with haloes, follicular mucin, and nucleomegaly / convolution in all four cases, prominent eosinophils (2), epithelioid granulomas (1), eccrine infiltration (4), parakeratosis at the follicular ostia (2), and sebaceotropism (1). The infiltrate was bulbar (4) and isthmic (2). The rest of the epidermis showed no hint of conventional MF. CONCLUSION: The preferential features for FMF were involvement of face, dominant folliculotropism, nuclear atypia and convolution, and follicular mucin. Presence of granulomas and eosinophils necessitated exclusion of infectious causes. The absence of findings of MF in the rest of the epidermis should not deter pathologists from rendering this diagnosis.

Intra-abdominal, crystal-storing histiocytosis due to clofazimine in a patient with lepromatous leprosy and concurrent carcinoma of the colon.

We report a case with abdominal complications of clofazimine treatment which included blackish discolouration of the lymph nodes, omentum and peritoneum. A 44-year-old female with lepromatous leprosy and a history of adverse reaction to clofazimine 2 years previously, presented with rectosigmoid junction adenocarcinoma. Laparotomy revealed an inoperable tumour with pigmentation of the bowel, serosa and peritoneum. A second operation had o be performed for transverse loop colostomy and a mesenteric lymph node biopsy sent for frozen section showed typical clofazimine crystals. Despite widespread use for many years in the treatment of leprosy, this drug is not known to be carcinogenic and this case provides no evidence for an association or link between its use and the patient's cancer. Apart from its use in leprosy, clofazimine may be used in the treatment of disseminated Mycobacterium avium-intracellulare infection, Buruli ulcer due to M. ulcerans and occasionally in other mycobacterial infections. An awareness of the rare side-effect described above may help in the clinical assessment and management of such cases, including the avoidance of unnecessary laparotomy.