Detection of HHV-8 in pyogenic granuloma-like Kaposi sarcoma

Kaposi sarcoma (KS) is a low-grade vascular neoplasm associated with human herpesvirus-8 (HHV-8) infection. Clinically, lesions commence as blue-red macules that may develop into plaques and eventually into nodules. The histologic appearance spans a broad spectrum and varies with the stage of the lesion. At each stage, KS has significant morphologic overlap with other vasoproliferative lesions. Recently, we encountered 6 KS tumors that histologically mimicked pyogenic granuloma (PG), a common benign vascular tumor of the skin that usually does not figure in the histologic differential diagnosis of KS. We stained 6 PG-like KS and 28 PGs with a mouse monoclonal antibody (13B10) against HHV-8 latent nuclear antigen-1 (LNA-1) to determine the utility of immunoperoxidase staining in distinguishing KS from PG. All 6 PG-like KS demonstrated nuclear staining for HHV-8 LNA-1. No staining was identified in any of the 28 PGs. Histologic criteria often used to differentiate between these two entities were not helpful in our cases. The only distinguishing feature was the presence or absence of HHV-8 LNA-1 staining. The presence of HHV-8 LNA-1 nuclear staining seems to be a specific marker for KS when comparing PGs and PG-like KS. Immunoperoxidase staining for HHV-8 LNA-1 is a useful diagnostic tool in this setting.     

Mycosis fungoides presenting as pigmented purpuric eruption

A case of pigmented purpuric eruptions evolving to mycosis fungoides during the 4-year follow-up period is described. Clinical manifestation was characterized by petechial lesions with irregular shaped, diffusely pigmented plaques partly sharing morphological similarities with chronic pigmented purpura. Histologically, lymphocytes infiltrated around the capillaries of the superficial dermis with extravasated erythrocytes as well as into the epidermis to form Pautrier microabscesses. Whereas CD4+ cells were observed in the epidermis and upper dermis, CD8+ cells tended to be distributed around the capillaries. Notably, the Rumpel-Leede test revealed extensive punctuate purpura limited to the lesional skin. The aggregation response of platelets was not impaired. Either CD4+ tumor lymphocytes or CD8+ reactive lymphocytes appeared to induce capillary damage resulting in the formation of petechial lesions. Pigmented purpuric eruptions, such as atypical chronic pigmented purpura, is thus an important initial clinical manifestation of mycosis fungoides.     

Bednár tumor associated with dermal melanocytosis: melanocytic colonization or neuroectodermal multidirectional differentiation?

BACKGROUND: Neuroectodermal differentiation or melanocytic colonization are the opposing theories of histogenesis for the Bednár tumor or pigmented dermatofibrosarcoma protuberans (DFSP). OBSERVATION: A 31-year-old African-American woman presented with a 2-cm blue-black shoulder nodule of 1-year duration. Punch biopsy revealed a CD34+, Factor XIIIa-DFSP, harboring numerous, pigmented spindle S100+, Mart-1+ and HMB-45+ cells. Subsequent wide excision demonstrated pigmented dendritic and spindled cells widely scattered throughout the dermis of the 3-cm excisional margins and punch biopsy specimens of normal skin from both shoulders. This latter process was interpreted as dermal melanocytosis (nevus of Ito). The dermal pigmented spindle cells were Mart-1+ and CD34-, and were associated with non-pigmented CD34+, cytologically banal spindle cells, which were more numerous in the excisional margins than the contralateral shoulder. CONCLUSION: Reported herein is a singular case of Bednár tumor associated with dermal melanocytosis. Although the coexistence of these processes implicates colonization of the DFSP by constituent dermal melanocytes, the mixed immunophenotype (CD34+ or Mart-1+ cells) of dispersed dermal spindle cells hints at the possibility of a common cell of origin: the putative neuromesenchymal cell. In effect, the Bednár tumor could represent one part of a spectrum of neural crest-derived dermal tumors that includes dermal melanocytosis, cellular blue nevus and conventional DFSP.     

Insect bite-like reaction associated with mantle cell lymphoma: clinicopathological, immunopathological, and molecular studies

A cutaneous eruption simulating insect bites has been repeatedly described in association with chronic lymphocytic leukemia (CLL). It was only rarely described with mantle cell lymphoma (MCL). Our study was performed to elucidate the clinical, histologic, immunopathological, and molecular characteristics of insect bite like reaction (IBLR) associated with MCL. The clinical presentation and histologic findings in 3 IBLR cases associated with MCL were found to be similar to 3 IBLR cases associated with CLL. The eruptions consisted of itchy erythematous papules, nodules, plaques, and vesicles. Non-vesicular lesions were characterized histologically by normal or mildly spongiotic epidermis. Vesicular lesions were characterized by marked spongiosis and intraepidermal spongiotic vesicles containing eosinophils, or marked subepidermal edema occasionally leading to a dermoepidermal separation. Most of the lesions were characterized by superficial and mid dermal to deep perivascular and interstitial, and occasionally periadnexal, inflammatory-cell infiltrate consisting of mononuclear cells and eosinophils. The densities of the infiltrates varied and the inflammatory-cell infiltrate extended often into the fat lobules. Neutrophils and nuclear dust were found more frequently and abundantly in the IBLR lesions associated with MCL. Immunophenotyping, direct immunofluorescence (DIF) tests, and IgH gene rearrangement studies were performed in the lesions associated with MCL only. The majority of the infiltrating lymphocytes were CD3+, CD5+ and CD43+, more CD4+ than CD8+, and only a small minority was CD20+. The cells did not stain for bcl-1 protein and CD30, and with no evidence of clonality. The DIF test result was negative. The IBLR eruption associated with MCL resembles clinically and histologically IBLR associated with CLL. The eruption seems to be reactive rather than neoplastic, because there is no evidence of MCL involvement in the skin lesions.     

Matrix metalloproteinases in the progression and regression of Kaposi's sarcoma

BACKGROUND: Matrix metalloproteinases (MMPs) are associated with Kaposi's sarcoma (KS) tumorigenesis. To date, only a few MMPs have been studied in KS lesions. Their role in KS regression has not been investigated. The aim of this study was to evaluate the expression of multiple MMPs in developing and pharmacologically regressed KS lesions. METHODS: Nine samples of acquired immune deficiency syndrome (AIDS)-related and classic cutaneous KS lesions at various histological stages were studied. Regressing KS lesions from three patients treated with systemic therapy were procured after one and two cycles of chemotherapy. Tissue sections from all specimens were immunostained using monoclonal antibodies to MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, and MMP-14. RESULTS: KS lesional cells were immunoreactive for all MMPs, except MMP-14. Admixed inflammatory cells were immunoreactive for MMP-1, MMP-2, MMP-7, MMP-9, and MMP-13. The MMP immunoprofile in residual KS lesional cells was unaltered in regressed lesions. Increased extracellular matrix (ECM) and macrophage immunoreactivity for MMPs was identified in regressed specimens. CONCLUSIONS: These data show that developing KS lesional cells express collagenases (MMP-1, MMP-13), gelatinases (MMP-2, MMP-9), stromelysin-1 (MMP-3), and matrilysin (MMP-7) but not the membrane-type MMP-14. This MMP expression profile is retained by residual KS cells and also expressed by infiltrating macrophages in regressed KS lesions. Pantanowitz L, Dezube BJ, Hernandez-Barrantes S, Tahan SR, Dabbous MK. Matrix metalloproteinases in the progression and regression of Kaposi's sarcoma.     

The Histopathology of Subcutaneous Minocycline Hyperpigmentation

A variety of benign and malignant cutaneous vascular lesions occur in irradiated skin. We report two cases of vascular lesions that developed on the breast within a year after radiation therapy for breast carcinoma. Both cases mimicked Kaposi's sarcoma (KS) histologically. We compare these with one case of post‐irradiation angiosarcoma and 3 cases of acquired progressive lymphangioma (APL) unrelated to radiation therapy. The post‐irradiation vascular lesions showed slit‐like vessels dissecting through superficial dermal collagen, leading to an initial diagnosis of KS by one contributing pathologist. Immunohistochemically, the vessels in both cases expressed CD31 and CD34, stained only partially for actin, and had a low Ki67 proliferation index. Neither case expressed HHV8. The post‐irradiation angiosarcoma occurred three years after radiation, and also exhibited a focal slit‐like growth pattern resembling KS. However, there was marked cytologic atypia, a high proliferation rate, and negative staining for HHV8. The APL were characterized by more ectactic vascular spaces and deeper involvement of the dermis than was present in the post‐irradiation lesions. These cases also failed to stain for HHV8. Recognition of the phenomenon of post‐irradiation vascular proliferations is important, especially because such lesions may resemble KS, yet invariably follow a benign clinical course.     

I Forgot to Shave My Hands: Spiny Keratoderma of the Palms and Soles

Lymphomatoid papulosis (LyP) is a cutaneous CD30+ lymphoproliferative disorder characterized by recurrent papulonecrotic or papulonodular lesions with histologic features of a malignant lymphoma and an excellent prognosis. Three morphologic types (A, B, and C) of LyP exist and typically display an immunophenotype of CD4+, CD8−, and CD30+. We present a case of a 63‐year‐old woman with a one‐year history of relapsing papulonecrotic skin eruptions. Biopsy of a lesion on the forearm showed a superficial and deep dermal wedge‐shaped infiltrate with large lymphoid cells (Type A LyP). A lesion on the abdomen showed a band‐like superficial dermal infiltrate composed of small lymphoid cells with extensive epidermotropism and cerebriform nuclei (Type B LyP). Lastly, a lesion on the buttock histologically showed a dense, diffuse dermal infiltrate composed of a mixture of small and large lymphoid cells (Type C LyP). In all three lesions, the atypical lymphocytes were immunoreactive to CD8 and CD30 and nonreactive to CD4. CD8 positive cases of LyP are rare in the literature and tend to occur in pediatric patients. Moreover, while approximately 10% of patients may present with lesions of both the type A and type B types, cases showing all three types of LyP are exceedingly rare.     

Lymphangioma-like Kaposi sarcoma

BACKGROUND: Lymphangioma-like Kaposi's sarcoma (LLKS) is a rare morphologic expression of Kaposi's sarcoma (KS) that occurs in virtually all of the well-recognized clinical subtypes of the disease and has the potential to mimic other pathologic processes. In this study, we present the clinical and pathological features of four patients with LLKS. METHODS: Four cases of LLKS were retrieved from the dermatopathology files of our institution. All four tumours were tested immunohistochemically with anti-human herpesvirus-8 (HHV-8) latent nuclear antigen-1 (LNA-1) and anti-CD34 antibodies. RESULTS: Clinically, each patient presented with violaceous patches, papules or plaques; one patient presented with bullous lesions. All of the LLKS biopsy specimens revealed areas with characteristic light microscopic features of KS. Lymphangioma-like foci consisted of ectatic, irregularly shaped vascular spaces lined by mildly atypical endothelial cells. All tumour cells, including those associated with LLKS foci, showed a strong and diffuse reactivity for anti-HHV-8 LNA-1 and anti-CD34. KS progressed slowly in two patients with adequate follow-up. CONCLUSIONS: As LLKS can mimic other disease processes, the correct diagnosis relies heavily on the recognition of salient clinical and histological features of conventional KS, including a strong immunohistochemical expression of HHV-8-associated LNA-1 in lesional cells.     

Lymphangioma-like pattern and anaplastic evolution in a case of classic Kaposi's sarcoma

Background Usually, classic Kaposi's sarcoma (KS) is clinically characterized by maculae, plaques and nodules and histologically by a proliferation of irregularly-shaped blood vessels, spindle cells and extravasated erythrocytes. The course is indolent. Very rarely, cases have been reported in which malignant transformation occurred with subsequent visceral diffusion. Observations A case of classic KS in an 82-year-old man is reported. Clinically, the lesion appeared lo be a nodule which grew rapidly to become an exophytic tumour mass. Histopathologically, it was characterized at the beginning by a lymphangioma-like pattern with subsequent frank anaplasia. The diagnosis of KS was based on lymph node examination which showed typical features. The patient died after 1 year. Conclusions Taking into account these unusual patterns we emphasize their importance in the differential diagnosis of KS from other angiomatous and anaplastic lesions.     

Congenital Myxoid and Pigmented Dermatofibrosarcoma Protuberans: A Case Report

Dermatofibrosarcoma protuberans (DFSP) is a low‐grade, mesenchymal, spindle cell tumor. In addition to the classical form characterized by a storiform pattern of tumor cells, pigmented (Bednar's tumor) and myxoid variants can be observed. Classical DFSP and Bednar's tumor are easily diagnosed. The myxoid variant represents a diagnostic challenge. Pigmented and myxoid variants are rare and thus far have never been reported in association in congenital DFSP. We came across a unique DFSP that was, at the same time, congenital, pigmented, and myxoid. The tumor was surgically excised with broad free margins and no recurrence. The differential diagnosis with other entities such as giant cell fibroblastoma, CD34‐positive plaque‐like dermal fibroma, superficial plaque‐like CD34 DFSP, and neurocristic hamartoma is discussed. The recognition of this hybrid variant of congenital DFSP is important to avoid under‐ or overtreatment.     

Regression of oral Kaposi''s sarcoma in a case of AIDS on Zidovudine (AZT)

A case with oral Kaposi's sarcoma (KS) is reported that regressed during therapy with Zidovudine (AZT) which was started 5 months after the first dermal and oral tumours were noted. After 6 months of treatment the absolute number of T-helper cells had increased from 54/microliters to 232/microliters and the ratio of T-helper to T-suppressor cells from 0.15 to 0.3. During the same time the lesions of KS on the gingiva, uvula and the body as well as the face disappeared. The lesion of KS on the hard palate regressed.     

Pre-Kaposi's sarcoma: an expansion of the spectrum of Kaposi's sarcoma lesions.

We report on a lymphoedematous form of classic Kaposi's sarcoma (KS) in which characteristic purplish lesions were surrounded by atypical oedematous, flesh-coloured papules. Histological examination of these papular lesions revealed a proliferation of grouped, rather thick-walled capillaries with inflammatory infiltrates. Hot-start PCR amplification with KS 330-233 primer sequences demonstrated the presence of human herpesvirus 8 (HHV-8) sequences. In addition, cells isolated from these oedematous papules showed morphological and immunohistochemical features similar to those reported for KS-derived spindle cells. As a whole, these results suggest that these oedematous papular lesions represent pre-KS lesions and may expand the clinico-pathological spectrum of KS. The role of oedema in their induction is discussed.     

Prurigo pigmentosa: role of ICAM-1 in the localization of the eruption

Immunohistochemical studies were carried out on the skin lesions of two cases of prurigo pigmentosa. There was a predominance of CD4+ cells in the dermal infiltrate, whereas those lymphocytes in the epidermis were mainly CD8+ cells. The majority of dermal and epidermotropic lymphocytes showed an intense expression of lymphocyte function-associated antigen 1 (LFA-1). The number of CD1+ cells was increased in the epidermis. There was intense expression of ICAM-1 by keratinocytes in the erythematous papules. Focal expression of ICAM-1 was still observed in the residual pigmented areas and could explain the recurrence of the lesions at these sites.     

Solitary sclerotic fibroma of skin: a possible link with pleomorphic fibroma with immunophenotypic expression for O13 (CD99) and CD34

BACKGROUND: Solitary sclerotic fibroma (SF) presents as a well circumscribed dermal nodule, composed of sparse spindle cells with alternating wavy collagen fibers arranged in a storiform pattern. The histogenesis and nature of this histologically distinct lesion are uncertain. Whether this peculiar tumor represents a true hamartoma or a degenerating end of various fibrous lesions such as pleomorphic fibroma (PF), dermatofibroma, or angiofibroma is still controversial. High proliferating index of spindle cells in SF argues against the possibility of being a degenerating end product of another lesion. METHODS: We studied morphological features and immunoprofile of eight SFs, in comparison with four PFs, one collagenized dermatofibroma, two angiofibromas, and two periungual fibromas. Immunostains for CD34, CD31, O13 (CD99), Factor XIIIa, S-100, CD68 (KP-1), and MIB-1 were carried out using a labeled streptavidin-biotin method with DAKO-automated immunostainer. Paraffin blocks of two SFs were reprocessed for electron microscopic studies. Clinical data of all patients with SF were also reviewed. RESULTS: Spindle cells and pleomorphic cells in SF and PF showed diffuse immunoreactivity for CD34 and O13 but were negative for CD31, S-100, and CD68. Spindle cells in one dermatofibroma and one angiofibroma were positive for Factor XIIIa. Proliferating index (MIB-1) was very low in all cases of SF, contradicting some previous reports. CONCLUSIONS: SF is a fibrotic lesion with cells positive for CD34 and O13. It shares a common immunoprofile with PF but is distinct from dermatofibroma and other common spindle cell lesions of skin. O13 expression in SF has not been previously described.     

Superficial dermal melanocytosis of the elderly: An exceptional occurrence?

The development of flat pigmented lesions on chronically sun-damaged (CSD) skin of the face may represent the clinical manifestation of a wide variety of hyperplastic/neoplastic melanocytic proliferations. We report the exceptional case of an acquired pigmented patch occurring on CSD skin, histopathologically characterized by diffuse hyperplasia of dendritic/spindled melanocytes in the superficial dermis within a widened band of actinic elastosis. This lesion was associated with a small focus of early invasive lentigo maligna melanoma (LMM). We show the melanocytic nature of the population of dermal pigmented cells by means of single and double immunohistochemical staining for melanocytic and histiocytic markers. The biologic significance of the focus of LMM within the hyperpigmented lesion (whether random collision phenomenon or causally related occurrence), as well as the pathogenesis of the whole dermal lesion are difficult to elucidate. Our case emphasizes the need for a better understanding of the pathophysiology of so-called dermal melanocytes.     

Two Cases of Vitiligo Developed on the Persisting Dermal Melanocytosis: Is There a Difference between Epidermal Melanocytes and Dermal Melanocytes?

Vitiligo is one of the most common pigmentary skin disorders; it is characterized by circumscribed depigmented macules due to the destruction of melanocytes. Although the etiology of vitiligo has not been fully elucidated, multiple factors including autoimmune and oxidative stress have been implicated in the pathogenesis of vitiligo. In contrast, dermal melanocytosis is histologically characterized by the presence of dermal melanocytes. It has been described that there are ectopic dermal melanocytes, which have failed to reach their proper location. A literature search revealed very few reports of patients with vitiligo developing vitiligo within dermal melanocytosis. Here, we report two cases of patients with vitiligo that occurred at pre-existing sites of dermal pigmented lesions. The histopathology showed the loss of epidermal melanocytes in spite of the existence of melanocytes in the dermis. There was no significant infiltration of inflammatory cells in the dermis. These cases illustrate unknown environmental factors as well as heterogeneity.     

Cutaneous sclerosing perineurioma of the digits: an uncommon soft-tissue neoplasm. Report of two cases with immunohistochemical analysis

BACKGROUND: Cutaneous sclerosing perineurioma is a recently characterized, uncommon tumor composed of perineurial cells, which exhibits immunoreactivity for epithelial membrane antigen (EMA). These lesions occur preferentially in children and young adults and usually develop as dermal or subcutaneous nodules in the hands or palms. METHODS: We report two cases of cutaneous sclerosing perineurioma in young patients without stigmata of neurofibromatosis. Histologically, these lesions were well-circumscribed masses and were characterized by a variable number of epithelioid and spindle cells with wavy nuclei end elongated cytoplasmic processes embedded in a dense collagen stroma. RESULTS: These cells showed focal whorling formation, demonstrated robust immunoreactivity for EMA and CD99, and were uniformly negative for S-100 protein, actin (HHF-35), CD34, cytokeratin AE1-3, and CD57. CONCLUSION: We comment on the differential diagnosis of fibrous cutaneous lesions based on immunohistochemistry.     

Compound blue nevus: a variant of blue nevus with an additional junctional dendritic component. A clinical, histopathologic, and immunohistochemical study of six cases

We studied six cases of heavily pigmented melanocytic lesions with features of blue nevi within the dermis, but with an additional junctional dendritic component. This compound variant of blue nevus is an uncommon lesion that has not been previously identified as a distinct histologic entity. Immunoperoxidase staining for S100 protein and counterstaining with azure B distinguished the presence of melanocytes among numerous melanophages within the dermis. The compound variant of blue nevus can be distinguished histologically from combined blue nevus, pigmented spindle cell nevus, malignant melanoma, and melanosis due to a regressed malignant melanoma. The six lesions were from three men and three women whose ages ranged from 11 to 51 years (mean, 31 years). Three lesions were located on the trunk, two on the extremities, and one on the head. After a mean follow-up period of 47 months (range, 38 to 58 months), there was no evidence of recurrence.     

Inverse correlation between CD34 expression and proline-4-hydroxyase immunoreactivity on spindle cells noted in hypertrophic scars and keloids

The CD34 positive (CD34+) spindle cells constitute a special population of spindle cells which show a unique distribution in the skin. So far, however, the functional role of CD34+ spindle cells and the regulation of CD34 expression on dermal spindle cells are totally unknown. We examined immunohistologically the pattern of the expression of CD34 and proline-4-hydroxylase, a marker for the fibroblasts that participate in active collagen synthesis, on dermal spindle cells at various stages of scar and keloidal tissues.
Dermal spindle cells in the lesions of hypertrophic scar and those at inflammatory expanding borders of keloids totally lost CD34 expression, but they strongly expressed proline-4-hydroxylase. On the other hand, they expressed CD34, together with decreased immunoreactivity to anti-proline-4-hydroxylase antibody, in non-inflammatory scars or in a non-inflammatory central portion of keloid. In two cases of scars, in which inflammation began to subside, double immunofluorescence demonstrated that both CD 34 and proline-4-hydroxylase were expressed on the same spindle cells.
CD34 expression, once disappeared from the lesions of hypertrophic scar or keloid, seems to return on CD34–proline-4-hydroxylase+ cells, when the initial inflammatory changes begin to regress. There is a reverse correlation between CD34 expression on spindle cells and the synthesis of type I collagen in the skin.     

Cellular digital fibromas: distinctive CD34-positive lesions that may mimic dermatofibrosarcoma protuberans

BACKGROUND: Digital fibromas are common benign acral tumors typically reported as angiofibromas (AFs) or acquired digital fibrokeratomas (ADFs). Cellular variants are not well recognized. METHODS: We collected 14 acral fibrocytic lesions showing a spindle cell morphology from our files, and evaluated CD34, Factor XIIIa, epithelial membrane antigen (EMA), and S100 protein staining of these lesions. We compared the histologic and immunohistochemical features of these cellular fibromas with five digital AFs, five ADFs, and five digital dermatofibromas. RESULTS: The 14 cellular digital fibromas showed intersecting fascicles of thin delicate bland spindle cells in the superficial reticular dermis with a fibrotic-to-slight myxoid stroma. The spindle cells in all cases stained strongly for CD34, and only scattered stromal cells stained for Factor XIIIa. Five tested cases were negative for EMA and S100 protein. The digital AFs, fibrokeratomas, and dermatofibromas stained predominately for Factor XIIIa, with no or minimal staining for CD34. CONCLUSIONS: These findings suggest that a subset of digital fibromas is characterized by a dense cellular proliferation of CD34-positive spindle cells. Awareness of this variant of digital fibroma and its staining pattern is critical in preventing misdiagnosis as dermatofibrosarcoma protuberans, particularly in superficial biopsies.