An unusual variant of lichen nitidus: Generalized follicular spinous with perifollicular granulomas

Several unusual variants of lichen nitidus are described in the literature. Spinous follicular lichen nitidus with perifollicular granulomas is one such variant characterized by generalized follicular as well as nonfollicular keratotic papules, which show perifollicular granulomas on histopathology as well as a lichenoid granulomatous tissue reaction typical of lichen nitidus. Owing to its atypical clinical and histopathologic manifestations, it raises several clinical possibilities and can be a diagnostic challenge. We report this rare variant of lichen nitidus in a 19-year-old female, and discuss its clinical and histopathological differential diagnosis.     

A rare case of lupoid leishmaniasis defying diagnosis for a decade

Cutaneous leishmaniasis (CL) is a common disease affecting millions in endemic areas worldwide. We present a case of lupoid leishmaniasis, a rare variant of CL, which clinically mimicked sarcoidosis and/or granulomatous rosacea for 10 years until ultimate diagnosis. An 82-year-old U.S. citizen with an extensive travel history presented with a 10-year history of facial plaques on the cheeks and was previously diagnosed and treated as sarcoidosis. Multiple biopsies (previously and at presentation) revealed tuberculoid granulomas with negative special stains for microorganisms and negative sterile tissue cultures for acid-fast bacilli, bacteria, and fungal organisms. A diagnosis of granulomatous rosacea was rendered and multiple medical therapies were attempted, none with sustained improvement. Repeat biopsy of a new lesion revealed intracellular organisms consistent with leishmaniasis, which was confirmed by polymerase chain reaction (PCR). Lupoid leishmaniasis is a rare presentation of CL including facial plaques that can mimic granulomatous diseases affecting the face including sarcoidosis and granulomatous rosacea. CL can sometimes be challenging to diagnose through standard histopathologic examination; immunohistochemistry for CD1a can be used to augment tissue-based examination and PCR should be sent early in cases with sufficient concern.     

A case of granulomatous rosacea: sorting granulomatous rosacea from other granulomatous diseases that affect the face

Granulomatous rosacea is a variant of rosacea that may present similar to other granulomatous diseases. We present the case of a 45-year-old woman with a 2-year history of facial erythema with multiple papules and pustules on the cheeks, chin, and glabella. The patient responded to minocycline, resulting in healing 6 months without residual scarring. This patient's clinical and histological presentation and treatment outcome are to our assessment consistent with granulomatous rosacea. However, other clinically and histologically related entities will be discussed. These entities include, but are not limited to, perioral dermatitis, granulomatous periorificial dermatitis, lupus miliaris disseminatus faciei, facial afro-caribbean eruption syndrome, and sarcoidosis.     

Perifollicular fibroma in Birt-Hogg-Dubé syndrome: an association revisited

Background: Mutation in the folliculin gene in Birt–Hogg–Dubé (BHD) syndrome leads to a spectrum of benign tumors of the hair follicle, classically including both fibrofolliculoma and trichodiscoma. In addition, lesions clinically indistinguishable from fibrofolliculoma/ trichodiscoma may show histopathologic findings of perifollicular fibroma or angiofibroma. Although some consider perifollicular fibroma to be a variant of angiofibroma, the specific histopathologic findings of perifollicular fibroma are uncommon. Methods: This is a case series. Results: In 4 patients with multiple facial lesions, recognizing perifollicular fibroma would have been helpful in leading to the diagnosis of BHD syndrome. Conclusion: Perifollicular fibroma is on a spectrum with fibrofolliculoma and trichodiscoma; in a patient with multiple lesions, the diagnosis of perifollicular fibroma is suggestive of BHD syndrome.     

Facial granulomatous diseases: a study of four cases tested for the presence of Mycobacterium tuberculosis DNA using nested polymerase chain reaction

The histopathologic diagnosis of cutaneous tuberculosis (CTB) is often troublesome, because there are several other entities (tuberculids, demodicidosis, granulomatous rosacea, and acne agminata) that may display granulomatous inflammation with caseation necrosis. The current study describes four cases of granulomatous disease of the face. The final diagnosis (assessed on the basis of the clinical response to therapy) was CTB in three cases and granulomatous rosacea in one case. Histologically, epithelioid granulomas were a constant feature; in one case of CTB, they displayed a palisading (granuloma annulare-like) arrangement. Caseation necrosis was a prominent feature only in the case of granulomatous rosacea. Routinely processed biopsy specimens were evaluated with nested polymerase chain reaction (nPCR) for Mycobacterium tuberculosis (MBT) DNA. The correlation between nPCR results and clinical outcome was less than optimal; in fact, one case showed an excellent clinical response to the antituberculous drug therapy despite the absence of MBT DNA amplification. In granulomatous diseases of the face, the importance of evaluating not only nPCR but the overall clinicopathologic picture so as to avoid diagnostic misinterpretations is emphasized.     

Lupus miliaris disseminatus faciei: a distinctive rosacea-like syndrome and not a granulomatous form of rosacea

BACKGROUND: Lupus miliaris disseminatus faciei is an eruption of discrete red-brown, dome-shaped papules, histologically characterized by epithelioid cell granulomas. The pathogenesis of the disorder remains controversial. OBJECTIVE: The authors discuss the place of lupus miliaris disseminatus faciei among granulomatous disorders. METHODS: This report reviews the available literature and presents 3 patients with lupus miliaris disseminatus faciei. RESULTS: The histopathologic characteristics of lupus miliaris disseminatus faciei--an epithelioid cell granuloma with central necrosis--may be found in granulomatous rosacea, whilst the clinical features and course of lupus miliaris disseminatus faciei are often similar to cutaneous sarcoidosis. CONCLUSIONS: We put forward lupus miliaris disseminatus faciei as a distinctive rosacea-like syndrome and not as a granulomatous form of rosacea.     

Histopathology attributes of Fox–Fordyce disease

Background Fox–Fordyce disease is a rare chronic papular condition with a very characteristic clinical presentation but a nonspecific histopathology. Its traditionally described histopathologic features have been criticized as variable and indistinct. Recently, a perifollicular infiltrate of histiocytes with foamy cytoplasm has been described as a consistent and reliable diagnostic finding. Methods To evaluate the traditional and most recently described histopathologic and immunohistochemical attributes of Fox–Fordyce disease, we performed a computerized search of specimens in two dermatopathologic databases in Puerto Rico from the years 2000–2010. An additional specimen was donated by a dermatopathologist from an outside institution. Three cases were evaluated using hematoxylin–eosin‐stained sections. The tip of an axillary lipoma excision specimen was used as the control tissue. Periodic acid‐Schiff, colloidal iron, and immunoperoxidase staining for CD68 and c‐kit (CD117) were performed in all specimens. Results We were able to verify traditionally described histological features such as infundibulum dilation, hyperkeratosis, plugging, acanthosis, and lymphohistiocytic infiltrate. Infundibular spongiosis was also common. A perifollicular foam cell infiltrate was the most distinct pathologic feature among our cases. The periodic acid‐Schiff staining patterns suggested that the foam cell cytoplasm material might be similar in nature to the apocrine gland secretion content. Conclusions Our results confirmed that a perifollicular foam cell infiltrate is the most distinct histopathologic feature. In addition, findings suggest that the intracytoplasmic foam cell material may be similar in nature to the apocrine gland secretion.     

Perioral dermatitis

Perioral dermatitis is a relatively common inflammatory facial skin disorder that predominantly affects women. It is rarely diagnosed in children. A typical perioral dermatitis presentation involves the eruption of papules and pustules that may recur over weeks to months, occasionally with fine scales. The differential diagnosis includes seborrheic dermatitis, systemic lupus erythematosus, acne vulgaris, lupus miliaris disseminatus faciei, polymorphous light eruption, steroid-induced rosacea, granulomatous perioral dermatitis, contact dermatitis (allergic and irritant), and even basal cell carcinoma. The histopathology is similar to that of rosacea, with a perivascular and perifollicular lymphohistiocytic infiltrate and sebaceous hyperplasia. The etiology of perioral dermatitis is unknown, but the uncritical use of topical corticosteroids often precedes skin lesions. Physical sunscreens with high sun protection factors may cause perioral dermatitis in children.     

Lethal T- and NK-cell lymphomas mimicking granulomatous panniculitidies: a clinicopathologic study of three cases

An infiltrate mimicking subcutaneous panniculitis associated with a granulomatous response represents an uncommon histopathologic presentation of lymphoma. We report three cases, comprising one case each of nasal-type extranodal NK/T-cell lymphoma, cutaneous γ/δ T-cell lymphoma and human T-lymphotropic virus-I associated adult T-cell leukemia/lymphoma, which based on initial histopathologic and/or clinical presentation were thought to represent systemic lupus erythematosus, sarcoidosis and psoriasiform dermatitis, respectively. Excisional biopsies of indurated lesions performed at our institute; however, in each case showed an atypical subcutaneous lymphohistiocytic infiltrate associated with a variable number of granulomas. Extensive immunophenotypic characterization, in conjunction with histomorphologic and molecular analysis, established the diagnosis of lymphoma in all instances. All patients had a rapidly progressive clinical course and death was attributable to complications of lymphoma shortly after diagnosis. These cases highlight the importance of using a multimodality diagnostic approach to distinguish lymphomas masquerading as granulomatous panniculitis from inflammatory or reactive disorders associated with such histopathologic patterns.     

Unusual histopathological features of cutaneous leishmaniasis identified by polymerase chain reaction specific for Leishmania on paraffin-embedded skin biopsies

BACKGROUND: Cutaneous leishmaniasis (CL) is rare in Northern Europe and may be overlooked because colleagues have little experience with it. OBJECTIVES: To identify manifestations of CL that may escape diagnosis. METHODS: Correlation of clinical diagnosis and histopathological findings in 28 biopsy specimens taken from 19 patients with CL confirmed by polymerase chain reaction (PCR) specific for Leishmania. RESULTS: In only one patient was the clinical diagnosis CL; other diagnoses included: malignant epithelial neoplasms (5), follicular cyst (2), atypical mycobacteriosis (1), sarcoidosis (2) and lymphoma (1). Lesions were single (15) or few (4) nodules predominantly situated on the extremities or face (16). Histopathological findings were diagnostic of CL in only 10 cases. In nine cases Leishmania was not identified microscopically; histopathological diagnoses were: granulomatous dermatitis (6), lupoid rosacea (1), foreign body granuloma (1) and granuloma annulare (1). Unaltered epidermis (9), nodular infiltrates (5), numerous multinucleated histiocytes (3), palisaded granulomas with fibrinoid centres (2), sarcoidal granulomas (4) and elastophagocytosis (1) misled the histopathologists in these cases. CONCLUSIONS: CL seems often to be misdiagnosed clinically in countries where it is not endemic. Histopathologically, CL may be misinterpreted as sarcoidosis, foreign body granuloma, lupoid rosacea and granuloma annulare, especially when Leishmania is not seen microscopically. We suggest that in Northern Europe, PCR for Leishmania-specific DNA should be performed routinely in any granulomatous dermatitis presenting as a single or few nodules on the extremities or face, even when a diagnosis of CL was not considered by the referring clinician.     

SECONDARY SYPHILIS: A CLINICOPATHOLOGIC STUDY

Background. With the resurgence of syphilis in the hiv era, a greater awareness of the clinicopathologic features of the disease is desirable. This report describes and correlates the clinical and histopathologic features of secondary syphilis seen at a teaching hospital in Delhi, India. Methods. Forty biopsies of mucocutaneous lesions from 31 consecutive patients with secondary syphilis, seen between September 1987 and January 1991, were studied and the histopathologic findings correlated with the clinical findings. Results. A spectrum of histopathologic changes ranging from a minimal infiltrate to granulomatous inflammation throughout the dermis was seen. The pattern of inflammation correlated well with the type of skin lesion, with macules showing the least and nodules the most prominent changes. The predominant cell type in the infiltrate was the mononuclear cell/lymphocyte. Plasma cells were seen infrequently. except in condylomata lata. Endothelial proliferation, the “classical” feature of the histopathology of syphilis was noted infrequently. Conclusions. The histologic manifestations of secondary syphilis appear to be as varied as the clinical ones. This calls for close interaction between the clinician and the pathologist to correlate the clinical, serologic, and histologic findings to establish the diagnosis of syphilis.     

Superficial granulomatous pyoderma: a case in an 11-year-old girl and review of the literature

Superficial granulomatous pyoderma is a rare entity thought to be a variant of pyoderma gangrenosum and is often mistaken for classic pyoderma gangrenosum. Superficial granulomatous pyoderma has mainly been described in adults. We describe a case of Superficial granulomatous pyoderma in an 11-year-old girl and present a review of the literature. Superficial granulomatous pyoderma maintains clinical and histopathologic characteristics distinct from classic pyoderma gangrenosum and has a more favorable prognosis. It is often responsive to conservative treatment.     

Perioral dermatitis

Perioral dermatitis is a relatively common inflammatory disorder of facial skin, often appearing in patients with rosacea, but with less inflammation. A typical perioral dermatitis presentation occurs with the eruption of papules and pustules confined to the nasolabial folds and the skin of the chin. Clinically, small pink papules and pustules may recur over weeks to months, sometimes with fine scales. The differential diagnosis includes seborrheic dermatitis, systemic lupus erythematosus, acne vulgaris, lupus miliaris disseminatus faciei, steroid-induced rosacea, and even basal cell carcinoma. The histopathology is similar to that found in rosacea. With advancement of the process, a perivascular and perifollicular lymphohistiocytic infiltrate develops. Sebaceous hyperplasia may be prominent in some patients. The most severe forms of disease show perifollicular noncaseating epithelioid granulomas. Treatment may include topical metronidazole as for rosacea (once or twice daily), azelaic acid cream, benzyl peroxide preparations, and to a lesser degree, topical erythromycin, clindamycin, or tetracycline. Oral tetracycline, doxycycline, or minocycline may also be helpful in presentations that are more resistant.     

Clinical presentations and classification of rosacea

Rosacea is a chronic skin disease affecting up to 10% of the population in some European countries. Rosacea manifests as various combinations of characteristic signs and symptoms in a centrofacial distribution. At present, there is no consensus about the definition or classification of the clinical patterns of rosacea. Initially, four stages were differentiated (pre-rosacea then stages I through III), with several variants (e.g., persistent erythema and edema, rosacea conglobata, and rosacea fulminans). The National Rosacea Society (NRS) in the USA has classified rosacea into four subtypes (erythematotelangiectatic, papulopustular, phymatous, and ocular) and one variant (lupoid or granulomatous rosacea). This classification scheme does not mention progression from one type to another and makes no reference to pathophysiological considerations. It uses major and minor diagnostic criteria based on the physical findings and symptoms. The NRS has also developed criteria for grading disease severity. The classification of rosacea into stages or subtypes, without considering the possibility of progression from one to another, will probably remain controversial until additional knowledge on the pathophysiology of rosacea is obtained.     

Progressive nodular histiocytoma

Progressive nodular histiocytoma is a clinically distinct variant in the general group of normolipemic histiocytic proliferations. Its cardinal feature is the presence of two different lesions--a superficial yellow-brown papule and a deep nodule. We describe herein a 29-year-old man with such lesions. Histologically, a variety of fibrous and cellular patterns were seen, mimicking the wide spectrum of findings in ordinary dermatofibromas. On ultrastructural examination, the most striking feature of the preponderant cell was lipid phagocytosis.     

Lupus miliaris disseminatus faciei: A resistant case with response to cyclosporine

Lupus miliaris disseminatus faciei (LMDF) is a chronic, inflammatory dermatosis of unknown etiology, characterized by multiple, monomorphic, symmetrical, reddish‐brown papules over forehead, cheeks, and eyelids. Histopathology shows perifollicular epitheloid cell granuloma. Though numerous therapies, ranging from cyclines, macrolides, dapsone tranilast, isotretinoin, steroids, and tacrolimus have been tried, the results are inconsistent, except with systemic steroids. One approach is to administer therapies based on the histological findings and the corresponding mode of action of drugs, thus antibiotics and dapsone are effective in the early inflammatory stage while clofazamine can be used in the granulomatous stage of the disease. A case of LMDF, recalcitrant to multiple systemic therapies, who responded dramatically to cyclosporine (50 mg twice daily), which probably was due to the specific effect on T_H1 cell response which mediates cell mediated immunity responsible for granulomatous changes on histology has been reported. This case highlights that LMDF is an independent granulomatous entity (not a variant of rosacea or tuberculosis).     

Interstitial granulomatous dermatitis with plaques

BACKGROUND: Interstitial granulomatous dermatitis is a histopathologic pattern with variable clinical appearance associated with autoimmune systemic diseases. The frequency of its different cutaneous expressions and its association with autoimmune diseases are not known. OBJECTIVE: We describe the clinical, serologic, and histologic features in 17 patients with interstitial granulomatous dermatitis with a clinical presentation consisting of large erythematous plaques. METHOD: Skin biopsy specimens fulfilling criteria for diagnosis of interstitial granulomatous dermatitis were selected and correlated with the clinical and laboratory findings. RESULTS: The study included 1 man and 16 women with multiple, asymptomatic, round to oval, erythematous plaques, most often on folds of the skin, in a bilateral and somewhat symmetric distribution. Most of patients had rheumatoid polyarthralgias along with various serologic abnormalities, often connected to collagen vascular diseases. Histologic examination disclosed a distinctive interstitial granulomatous dermatitis characterized by a diffuse infiltration of the interstitium by histiocytes with piecemeal fragmentation of collagen and formation of small granulomas around degenerative areas in concert with variable numbers of polymorphonuclear leukocytes sprinkled within the infiltrate. Churg-Strauss granulomas in miniature and flame figures were occasionally observed and indicated continued or increased activity of the associated autoimmune disease(s). CONCLUSIONS: Interstitial granulomatous dermatitis with plaques is a distinct entity with highly reproducible clinical and histopathologic features; recognition of these features identifies a patient who may have an underlying systemic autoimmune disorder.     

Erfolgreiche Therapie einer granulomatösen Rosazea mit Dapson

Granulomatous rosacea is an uncommon variant of rosacea. It is characterized by disseminated, red-brown papules and nodules especially in periocular and centrofacial locations. This form of rosacea causes considerable distress among patients because of the inflammatory facial lesions and represents a therapeutic challenge. A 62-year old man with granulomatous rosacea failed to improve with systemic doxycycline. Systemic isotretinoin and corticosteroids produced only a temporary reduction in cutaneous findings. Finally, systemic treatment with dapsone resulted in remission of the skin lesions and long-term stabilization.     

Non‐infectious granulomatous dermatoses

Granulomatous dermatoses comprise a wide range of etiologically and clinically distinct skin diseases that share a common histology characterized by the accumulation of histiocytes include macrophages. While the pathogenesis of these disorders is not fully understood, the underlying mechanism is thought to involve a reaction pattern caused by an immunogenic stimulus. Antigen‐presenting cells and the effect of various cytokines play a key role. Our understanding of granulomatous reaction patterns has been advanced by insights drawn from observations of such reactions in patients on immunomodulatory therapy and in individuals with genetic immunodeficiency. Traditionally, a distinction is made between infectious and non‐infectious granulomatous dermatoses. The present CME article addresses granulomatous skin diseases for which there is no evidence of a causative infectious agent. Common representatives include granuloma annulare, necrobiosis lipoidica and cutaneous sarcoidosis. Granulomatous dermatoses may be part of the clinical spectrum of various systemic disorders or may be associated therewith. Some neoplastic disorders may mimic granulomatous dermatoses histologically. Given the pathogenetic diversity involved, the clinical presentation, too, is quite varied. Overall, however, each disorder is characterized by typical clinical features. The diagnosis always requires thorough clinicopathologic correlation. Treatment is preferably based on the underlying pathogenesis and frequently involves anti‐inflammatory agents. In most cases, however, there is insufficient study data. The dermal nature of these disorders frequently poses a therapeutic challenge, especially with respect to topical treatment.     

Sea-urchin granuloma: histologic profile. A pathologic study of 50 biopsies

BACKGROUND: Sea-urchin granuloma is a chronic granulomatous skin lesion caused by injury with sea-urchin spines. Frequently these lesions occur on the hands and develop several months after the initial injury. Classified as an allergic foreign-body reaction, their most common histological pattern resembles sarcoid. The purpose of this study was to evaluate the light microscopic features of biopsies from lesions clinically diagnosed of sea-urchin granolomas. METHODS: We retrospectively reviewed 50 biopsy specimens corresponding to 35 patients with sea-urchin granulomas. These lesions were caused by injuries with the spines of the sea-urchin Paracentrotus lividus. Data were collected between 1990 and 1999 from patients in the seashore of Galicia (NW Atlantic coast, Spain). RESULTS: The cohort consisted of 35 patients (31 males, 4 females), with a median age of 35 years (range 14-60 years). The median duration of the disease was 7.5 months (range 2-60 months). We identified different histopathologic patterns. A granulomatous reaction was observed in 39 biopsies (78%). In 70% corresponding to 35 biopsies this granulomatous reaction was predominant. Foreign-body, sarcoidal, tuberculoid, necrobiotic and suppurative granulomas were identified. The remaining 15 biopsies (30%) showed a predominant inflammatory reaction with features of non-specific chronic inflammation or suppurative dermatitis. A panel of histopathologic features, including epidermal and dermal changes were evaluated. Presence of focal necrosis and microabscesses were common findings. In 50% of our specimens we found umbilication and/or perforation. Additional features included the presence of inclusion epidermoid cysts in four cases and squamous syringometaplasia in one case. CONCLUSIONS: Our observations suggest that sea-urchin granuloma span a wide morphologic spectrum. A granulomatous inflammatory reaction was predominant, with the foreign body and sarcoidal types the most frequent patterns. Other histopathologic patterns with non granulomatous inflammation can be noted. Some features, such as the frequency of perforation and the presence of necrobiotic granulomas have not previously been recognized in the literature.