Case 1.
The patient presented with an ulcerative plaque of the lower extremity, which was biopsied. Based on the following images, the best diagnosis is:
a) Catastrophic antiphospholipid-antibody syndrome
b) Calciphylaxis
c) Erythema induratum
d) Purpura fulminans
Case 2.
The patient has a well-known history of lupus erythematosus and now presents with multiple, dusky, erythematous lesions with concomitant bullae formation. The following images represent the diagnosis of:
a) Rowell’s syndrome
b) Phototoxic drug reaction
c) Acute graft versus host-disease
d) Atopic dermatitis
Case 3.
The patient was a previously well 71-year-old male who presented with relatively sudden onset of an intensely pruritic rash predominantly involving the back and extensor aspects of the upper extremities. A biopsy was performed. Based on the following slides, the correct diagnosis in this case is:
a) Bullous pemphigoid
b) Anti-epiligrin pemphigoid
c) Epidermolysis bullosa acquisita
d) P200 pemphigoid
Case 4.
A 46-year-old man presented with a pruritic rash over his body for many years prior to the initial diagnosis. In addition, he reported waxing and waning lymphadenopathy in the inguinal and cervical regions. His biopsies had always been interpreted as an eczematous dermatitis likely reflective of an atopic diathesis. He was treated with various topical treatments with no improvement. On examination, he had a dry and scaling skin on his face, back and arms as well as erythematous plaques on his feet. The patient had significant posterior cervical, bilateral axillary and bilateral inguinally lymphadenopathy diagnostic of a peripheral T cell lymphoma. Based on the following images, the correct diagnosis is:
a) Lymphomatoid papulosis
b) Atopic eczema
c) Drug rash with eosinophilia and systemic symptoms syndrome
d) Vesicular mycosis fungoides
Quiz Answers
Case 1 — B
Calciphylaxis
The biopsy shows highly characteristic features of calciphylaxis, a distinct form of calcific thrombotic microangiopathy. The low power view shows an intact epidermis and dermis, while the brunt of the pathologic alterations are present within the subcutaneous fat, findings that are more apparent in panels B, C and D.
In panel B, there is a pauci-inflammatory thrombogenic vasculopathy localized to vessels of the subcutaneous fat without similar changes present in the overlying dermis. In panel C, the highly characteristic arteriopathy is noted, characterized by intimal expansion by calcium. Panel D illustrates the von Kossa preparation, which is specific for calcium, showing a black stippled reaction pattern within the microvasculature corroborative of the presence of calcium within the thrombosed vessels.
The term “calciphylaxis” was originally introduced by Hans Seyle in 1961 to characterize a specific state characterized by sudden precipitous deposition of calcium in the soft tissue of animals under a unique set of sensitizing factors that antedate the calcification, such as hyperparathyroidism in concert with subsequent triggers that would provoke calcium deposition, most notably trauma. The first case of clinical calciphylaxis was in 1969 by Rees and Cole.
Calciphylaxis is now associated with a distinct syndromic complex in humans separate from experimental calciphylaxis. In human calciphylaxis, there is tissue compromise attributable to unique microangiopathy that combines features of both vascular thrombosis and endoluminal calcification. While early reports were primarily in the context of patients who were in renal failure on chronic emodialysis, calciphylaxis can occur in diverse clinical settings including cirrhosis, multiple myeloma, POEMS syndrome, protein C and S deficiency, obesity, rapid weight loss, connective tissue disease and infections.
Likely, 2 critical factors contribute to calcipylaxis. The first is an underlying procoagulant state. Indeed, a significant percentage of patients with calciphylaxis will have antiphospholipid antibodies and/or a significant reduction in critical anticoagulant factors such as protein C and protein S. The second factor likely relates to enhanced osteopontin production. Osteopontin is a phosphorylated matrix protein that is synthesized by various cell types including smooth muscle within the vessel wall under the influence of high levels of uric acid. This protein has a unique affinity for hydroxyapatite and is also a critical regulator of extramedullary deposition of calcium. Not surprisingly, the other conditions unrelated to renal failure, in which calciphylaxis is described, are those where higher levels of osteopontin can be observed.
Case 2 — A
Rowell’s syndrome
The biopsy is compatible with Rowell’s syndrome. In Rowell’s syndrome, one characteristically observes a severe cytotoxic interface dermatitis that can range in quality from a pattern resembling erythema multiforme to one more typical for toxic epidermal necrolysis. As one can see, in this particular biopsy, there is very extensive epidermal necrosis in a fashion reminiscent of toxic epidermal necrolysis versus erythema multiforme. In panel C, where there is full-thickness necrosis unaccompanied by significant lymphocyte satellitosis, the pattern is more toxic epidermal necrolysis-like. In panel D, the background changes that one associates with lupus erythematosus, namely an atrophying interface dermatitis with marked follicular involvement with follicular hyperkeratosis, is an important clue pointing toward a diagnosis of Rowell’s syndrome.
Rowell’s syndrome is a distinct variant of lupus erythematosus, which combines an overlapping morphology clinically of lupus erythematosus with erythema multiforme. These patients frequently have antibodies to Ro and as well may have concomitant changes of chilblains lupus erythematosus. The exact pathogenetic basis of Rowell’s syndrome is unclear. One might postulate an exogenous trigger such as a drug. However, there is an increasing body of literature that suggests that its etiologic basis may be one related to a true cytotoxic type IV immune response directed at endogenous antigenic epitopes. For example, an important serologic hallmark of Rowell’s syndrome is one of antibodies to Ro. Indeed, clonal expansion of T cells directed at the Ro antigen has been shown in experimental studies.
One should always consider a diagnosis of Rowell’s syndrome when there is a patient who has a known history of lupus erythematosus but with concomitant clinical features of erythema multiforme, often in the setting of antibodies to Ro. Direct immunofluorescent studies will characteristically show a positive lupus band test of all isotypes (ie, a full house immunoglobulin pattern) along with extensive decoration of keratinocytes for immunoglobulin G and complement reflective of the presence of antibodies to Ro.
Case 3 — B
Anti-epiligrin pemphigoid
The biopsy findings are characteristic of anti-epiligrin pemphigoid. In a minority of cases, the biopsy will show a neutrophil rich subepidermal blistering dermatosis reminiscent of other subepidermal blistering dermatoses, such as bullous systemic lupus erythematosus, linear IgA disease, P200 pemphigoid and inflammatory epidermolysis bullosa acquisita, a finding well-exemplified by this case.
In Panel B, there are linear deposits of immunoglobulin G (IgG) demonstrating dermal localization within the epidermal basement membrane zone. Circulating IgG antibodies react with the dermal side of a saline induced split skin devoid in collagen VII, and circulating IgG antibodies to laminin 5 detected by immunoblotting or immunoprecipitation. In Panel C, an indirect immunofluorescent assay is conducted utilizing patient’s serum and skin devoid in type VII collagen, a positive result is identified because immunoreactivity is not dependent the type VII antigenic epitope. In Panel D, salt split skin studies performed on the patient’s skin biopsy shows localization of immunoreactivity to the floor of the saline induced split. The antibody activity is against laminin 5, which also falls under alternative names including laminin 332, epiligrin, calanin and nicien. The actual molecular composition of laminin 5 is one comprising a heterodimer defined by 3 distinct chains designated alpha 3, beta 3 and gamma 2, respectively. The vast majority of patients who have this form of cicatricial pemphigoid have antibodies against the alpha 3 subunit. The association of anti-epiligrin pemphigoid with underlying malignancy may be related to the expression of laminin 5 by certain types of malignancies. Its high mortality reflects the underlying high-grade malignancy and immunosuppressive sequelae of iatrogenic drug therapy.
Case 4 — D
Vesicular mycosis fungoides
Although the diagnosis was obscured by vesiculation, there are important clues pointing to the correct diagnosis. In all cases, a very atypical, cerebriform, epitheliotropic, lymphocytic infiltrate was present. The intraepidermal lymphoid atypia characteristically exceeds that noted in the epidermis. The background architectural disposition of basilar colonization of the epidermis by atypical lymphocytes is a fairly ubiquitous finding. When one considers a conventional eczematous dermatitis, this pattern of passive interface dermatitis is not a feature. However, the most important clue is the mucinous quality of the vesicles essentially recapitulating follicular mucinosis. The abnormal lymphoid populace is of the CD4 (Panel C) subset exhibiting striking reductions in the expression of CD7 (Panel D) typical for plaque stage mycosis fungoides.
There are 6 prior cases of vesicular mycosis fungoides reported in the literature. In those cases exhibiting vesicular both clinically and histologically, the clinical course has been aggressive. Three of the 6 cases reported in the literature demonstrated lymph node involvement. In our experience, we have encountered 4 similar cases of which 2 of the cases have exhibited lymph node involvement.
The basis of the vesiculation could be reflective of a Th2 dominant cytokine microenvironment analogous to that seen in the setting of atopic eczema. It is well-established that conversion from a Th1 dominant microenvironment to one associated with a Th2 profile correlates with a more aggressive clinical course in the setting of mycosis fungoides, and hence could explain the association between vesicular mycosis fungoides and a more aggressive clinical course.
Dr. Magro is the director of dermatopathology at the Weill CornellMedical College in Manhattan NY, and is board certified in anatomic pathology, dermatopathology and cytopathology.
Dr. Magro is an expert in the diagnosis of complex inflammatory skin diseases. Her areas of expertise include cutaneous manifestations of autoimmune disease, systemic viral disease and vasculitis, atypical drug reactions, benign, atypical and overtly malignant lymphocytic infiltrates of the skin and diagnostically difficult melanocytic proliferations.
For more information, please visit www.weillcornelldermpath.com.
Disclosure: The author reports no relevant financial relationships.
Case 1.
The patient presented with an ulcerative plaque of the lower extremity, which was biopsied. Based on the following images, the best diagnosis is:
a) Catastrophic antiphospholipid-antibody syndrome
b) Calciphylaxis
c) Erythema induratum
d) Purpura fulminans
Case 2.
The patient has a well-known history of lupus erythematosus and now presents with multiple, dusky, erythematous lesions with concomitant bullae formation. The following images represent the diagnosis of:
a) Rowell’s syndrome
b) Phototoxic drug reaction
c) Acute graft versus host-disease
d) Atopic dermatitis
Case 3.
The patient was a previously well 71-year-old male who presented with relatively sudden onset of an intensely pruritic rash predominantly involving the back and extensor aspects of the upper extremities. A biopsy was performed. Based on the following slides, the correct diagnosis in this case is:
a) Bullous pemphigoid
b) Anti-epiligrin pemphigoid
c) Epidermolysis bullosa acquisita
d) P200 pemphigoid
Case 4.
A 46-year-old man presented with a pruritic rash over his body for many years prior to the initial diagnosis. In addition, he reported waxing and waning lymphadenopathy in the inguinal and cervical regions. His biopsies had always been interpreted as an eczematous dermatitis likely reflective of an atopic diathesis. He was treated with various topical treatments with no improvement. On examination, he had a dry and scaling skin on his face, back and arms as well as erythematous plaques on his feet. The patient had significant posterior cervical, bilateral axillary and bilateral inguinally lymphadenopathy diagnostic of a peripheral T cell lymphoma. Based on the following images, the correct diagnosis is:
a) Lymphomatoid papulosis
b) Atopic eczema
c) Drug rash with eosinophilia and systemic symptoms syndrome
d) Vesicular mycosis fungoides
Quiz Answers
Case 1 — B
Calciphylaxis
The biopsy shows highly characteristic features of calciphylaxis, a distinct form of calcific thrombotic microangiopathy. The low power view shows an intact epidermis and dermis, while the brunt of the pathologic alterations are present within the subcutaneous fat, findings that are more apparent in panels B, C and D.
In panel B, there is a pauci-inflammatory thrombogenic vasculopathy localized to vessels of the subcutaneous fat without similar changes present in the overlying dermis. In panel C, the highly characteristic arteriopathy is noted, characterized by intimal expansion by calcium. Panel D illustrates the von Kossa preparation, which is specific for calcium, showing a black stippled reaction pattern within the microvasculature corroborative of the presence of calcium within the thrombosed vessels.
The term “calciphylaxis” was originally introduced by Hans Seyle in 1961 to characterize a specific state characterized by sudden precipitous deposition of calcium in the soft tissue of animals under a unique set of sensitizing factors that antedate the calcification, such as hyperparathyroidism in concert with subsequent triggers that would provoke calcium deposition, most notably trauma. The first case of clinical calciphylaxis was in 1969 by Rees and Cole.
Calciphylaxis is now associated with a distinct syndromic complex in humans separate from experimental calciphylaxis. In human calciphylaxis, there is tissue compromise attributable to unique microangiopathy that combines features of both vascular thrombosis and endoluminal calcification. While early reports were primarily in the context of patients who were in renal failure on chronic emodialysis, calciphylaxis can occur in diverse clinical settings including cirrhosis, multiple myeloma, POEMS syndrome, protein C and S deficiency, obesity, rapid weight loss, connective tissue disease and infections.
Likely, 2 critical factors contribute to calcipylaxis. The first is an underlying procoagulant state. Indeed, a significant percentage of patients with calciphylaxis will have antiphospholipid antibodies and/or a significant reduction in critical anticoagulant factors such as protein C and protein S. The second factor likely relates to enhanced osteopontin production. Osteopontin is a phosphorylated matrix protein that is synthesized by various cell types including smooth muscle within the vessel wall under the influence of high levels of uric acid. This protein has a unique affinity for hydroxyapatite and is also a critical regulator of extramedullary deposition of calcium. Not surprisingly, the other conditions unrelated to renal failure, in which calciphylaxis is described, are those where higher levels of osteopontin can be observed.
Case 2 — A
Rowell’s syndrome
The biopsy is compatible with Rowell’s syndrome. In Rowell’s syndrome, one characteristically observes a severe cytotoxic interface dermatitis that can range in quality from a pattern resembling erythema multiforme to one more typical for toxic epidermal necrolysis. As one can see, in this particular biopsy, there is very extensive epidermal necrosis in a fashion reminiscent of toxic epidermal necrolysis versus erythema multiforme. In panel C, where there is full-thickness necrosis unaccompanied by significant lymphocyte satellitosis, the pattern is more toxic epidermal necrolysis-like. In panel D, the background changes that one associates with lupus erythematosus, namely an atrophying interface dermatitis with marked follicular involvement with follicular hyperkeratosis, is an important clue pointing toward a diagnosis of Rowell’s syndrome.
Rowell’s syndrome is a distinct variant of lupus erythematosus, which combines an overlapping morphology clinically of lupus erythematosus with erythema multiforme. These patients frequently have antibodies to Ro and as well may have concomitant changes of chilblains lupus erythematosus. The exact pathogenetic basis of Rowell’s syndrome is unclear. One might postulate an exogenous trigger such as a drug. However, there is an increasing body of literature that suggests that its etiologic basis may be one related to a true cytotoxic type IV immune response directed at endogenous antigenic epitopes. For example, an important serologic hallmark of Rowell’s syndrome is one of antibodies to Ro. Indeed, clonal expansion of T cells directed at the Ro antigen has been shown in experimental studies.
One should always consider a diagnosis of Rowell’s syndrome when there is a patient who has a known history of lupus erythematosus but with concomitant clinical features of erythema multiforme, often in the setting of antibodies to Ro. Direct immunofluorescent studies will characteristically show a positive lupus band test of all isotypes (ie, a full house immunoglobulin pattern) along with extensive decoration of keratinocytes for immunoglobulin G and complement reflective of the presence of antibodies to Ro.
Case 3 — B
Anti-epiligrin pemphigoid
The biopsy findings are characteristic of anti-epiligrin pemphigoid. In a minority of cases, the biopsy will show a neutrophil rich subepidermal blistering dermatosis reminiscent of other subepidermal blistering dermatoses, such as bullous systemic lupus erythematosus, linear IgA disease, P200 pemphigoid and inflammatory epidermolysis bullosa acquisita, a finding well-exemplified by this case.
In Panel B, there are linear deposits of immunoglobulin G (IgG) demonstrating dermal localization within the epidermal basement membrane zone. Circulating IgG antibodies react with the dermal side of a saline induced split skin devoid in collagen VII, and circulating IgG antibodies to laminin 5 detected by immunoblotting or immunoprecipitation. In Panel C, an indirect immunofluorescent assay is conducted utilizing patient’s serum and skin devoid in type VII collagen, a positive result is identified because immunoreactivity is not dependent the type VII antigenic epitope. In Panel D, salt split skin studies performed on the patient’s skin biopsy shows localization of immunoreactivity to the floor of the saline induced split. The antibody activity is against laminin 5, which also falls under alternative names including laminin 332, epiligrin, calanin and nicien. The actual molecular composition of laminin 5 is one comprising a heterodimer defined by 3 distinct chains designated alpha 3, beta 3 and gamma 2, respectively. The vast majority of patients who have this form of cicatricial pemphigoid have antibodies against the alpha 3 subunit. The association of anti-epiligrin pemphigoid with underlying malignancy may be related to the expression of laminin 5 by certain types of malignancies. Its high mortality reflects the underlying high-grade malignancy and immunosuppressive sequelae of iatrogenic drug therapy.
Case 4 — D
Vesicular mycosis fungoides
Although the diagnosis was obscured by vesiculation, there are important clues pointing to the correct diagnosis. In all cases, a very atypical, cerebriform, epitheliotropic, lymphocytic infiltrate was present. The intraepidermal lymphoid atypia characteristically exceeds that noted in the epidermis. The background architectural disposition of basilar colonization of the epidermis by atypical lymphocytes is a fairly ubiquitous finding. When one considers a conventional eczematous dermatitis, this pattern of passive interface dermatitis is not a feature. However, the most important clue is the mucinous quality of the vesicles essentially recapitulating follicular mucinosis. The abnormal lymphoid populace is of the CD4 (Panel C) subset exhibiting striking reductions in the expression of CD7 (Panel D) typical for plaque stage mycosis fungoides.
There are 6 prior cases of vesicular mycosis fungoides reported in the literature. In those cases exhibiting vesicular both clinically and histologically, the clinical course has been aggressive. Three of the 6 cases reported in the literature demonstrated lymph node involvement. In our experience, we have encountered 4 similar cases of which 2 of the cases have exhibited lymph node involvement.
The basis of the vesiculation could be reflective of a Th2 dominant cytokine microenvironment analogous to that seen in the setting of atopic eczema. It is well-established that conversion from a Th1 dominant microenvironment to one associated with a Th2 profile correlates with a more aggressive clinical course in the setting of mycosis fungoides, and hence could explain the association between vesicular mycosis fungoides and a more aggressive clinical course.
Dr. Magro is the director of dermatopathology at the Weill CornellMedical College in Manhattan NY, and is board certified in anatomic pathology, dermatopathology and cytopathology.
Dr. Magro is an expert in the diagnosis of complex inflammatory skin diseases. Her areas of expertise include cutaneous manifestations of autoimmune disease, systemic viral disease and vasculitis, atypical drug reactions, benign, atypical and overtly malignant lymphocytic infiltrates of the skin and diagnostically difficult melanocytic proliferations.
For more information, please visit www.weillcornelldermpath.com.
Disclosure: The author reports no relevant financial relationships.
Case 1.
The patient presented with an ulcerative plaque of the lower extremity, which was biopsied. Based on the following images, the best diagnosis is:
a) Catastrophic antiphospholipid-antibody syndrome
b) Calciphylaxis
c) Erythema induratum
d) Purpura fulminans
Case 2.
The patient has a well-known history of lupus erythematosus and now presents with multiple, dusky, erythematous lesions with concomitant bullae formation. The following images represent the diagnosis of:
a) Rowell’s syndrome
b) Phototoxic drug reaction
c) Acute graft versus host-disease
d) Atopic dermatitis
Case 3.
The patient was a previously well 71-year-old male who presented with relatively sudden onset of an intensely pruritic rash predominantly involving the back and extensor aspects of the upper extremities. A biopsy was performed. Based on the following slides, the correct diagnosis in this case is:
a) Bullous pemphigoid
b) Anti-epiligrin pemphigoid
c) Epidermolysis bullosa acquisita
d) P200 pemphigoid
Case 4.
A 46-year-old man presented with a pruritic rash over his body for many years prior to the initial diagnosis. In addition, he reported waxing and waning lymphadenopathy in the inguinal and cervical regions. His biopsies had always been interpreted as an eczematous dermatitis likely reflective of an atopic diathesis. He was treated with various topical treatments with no improvement. On examination, he had a dry and scaling skin on his face, back and arms as well as erythematous plaques on his feet. The patient had significant posterior cervical, bilateral axillary and bilateral inguinally lymphadenopathy diagnostic of a peripheral T cell lymphoma. Based on the following images, the correct diagnosis is:
a) Lymphomatoid papulosis
b) Atopic eczema
c) Drug rash with eosinophilia and systemic symptoms syndrome
d) Vesicular mycosis fungoides
Quiz Answers
Case 1 — B
Calciphylaxis
The biopsy shows highly characteristic features of calciphylaxis, a distinct form of calcific thrombotic microangiopathy. The low power view shows an intact epidermis and dermis, while the brunt of the pathologic alterations are present within the subcutaneous fat, findings that are more apparent in panels B, C and D.
In panel B, there is a pauci-inflammatory thrombogenic vasculopathy localized to vessels of the subcutaneous fat without similar changes present in the overlying dermis. In panel C, the highly characteristic arteriopathy is noted, characterized by intimal expansion by calcium. Panel D illustrates the von Kossa preparation, which is specific for calcium, showing a black stippled reaction pattern within the microvasculature corroborative of the presence of calcium within the thrombosed vessels.
The term “calciphylaxis” was originally introduced by Hans Seyle in 1961 to characterize a specific state characterized by sudden precipitous deposition of calcium in the soft tissue of animals under a unique set of sensitizing factors that antedate the calcification, such as hyperparathyroidism in concert with subsequent triggers that would provoke calcium deposition, most notably trauma. The first case of clinical calciphylaxis was in 1969 by Rees and Cole.
Calciphylaxis is now associated with a distinct syndromic complex in humans separate from experimental calciphylaxis. In human calciphylaxis, there is tissue compromise attributable to unique microangiopathy that combines features of both vascular thrombosis and endoluminal calcification. While early reports were primarily in the context of patients who were in renal failure on chronic emodialysis, calciphylaxis can occur in diverse clinical settings including cirrhosis, multiple myeloma, POEMS syndrome, protein C and S deficiency, obesity, rapid weight loss, connective tissue disease and infections.
Likely, 2 critical factors contribute to calcipylaxis. The first is an underlying procoagulant state. Indeed, a significant percentage of patients with calciphylaxis will have antiphospholipid antibodies and/or a significant reduction in critical anticoagulant factors such as protein C and protein S. The second factor likely relates to enhanced osteopontin production. Osteopontin is a phosphorylated matrix protein that is synthesized by various cell types including smooth muscle within the vessel wall under the influence of high levels of uric acid. This protein has a unique affinity for hydroxyapatite and is also a critical regulator of extramedullary deposition of calcium. Not surprisingly, the other conditions unrelated to renal failure, in which calciphylaxis is described, are those where higher levels of osteopontin can be observed.
Case 2 — A
Rowell’s syndrome
The biopsy is compatible with Rowell’s syndrome. In Rowell’s syndrome, one characteristically observes a severe cytotoxic interface dermatitis that can range in quality from a pattern resembling erythema multiforme to one more typical for toxic epidermal necrolysis. As one can see, in this particular biopsy, there is very extensive epidermal necrosis in a fashion reminiscent of toxic epidermal necrolysis versus erythema multiforme. In panel C, where there is full-thickness necrosis unaccompanied by significant lymphocyte satellitosis, the pattern is more toxic epidermal necrolysis-like. In panel D, the background changes that one associates with lupus erythematosus, namely an atrophying interface dermatitis with marked follicular involvement with follicular hyperkeratosis, is an important clue pointing toward a diagnosis of Rowell’s syndrome.
Rowell’s syndrome is a distinct variant of lupus erythematosus, which combines an overlapping morphology clinically of lupus erythematosus with erythema multiforme. These patients frequently have antibodies to Ro and as well may have concomitant changes of chilblains lupus erythematosus. The exact pathogenetic basis of Rowell’s syndrome is unclear. One might postulate an exogenous trigger such as a drug. However, there is an increasing body of literature that suggests that its etiologic basis may be one related to a true cytotoxic type IV immune response directed at endogenous antigenic epitopes. For example, an important serologic hallmark of Rowell’s syndrome is one of antibodies to Ro. Indeed, clonal expansion of T cells directed at the Ro antigen has been shown in experimental studies.
One should always consider a diagnosis of Rowell’s syndrome when there is a patient who has a known history of lupus erythematosus but with concomitant clinical features of erythema multiforme, often in the setting of antibodies to Ro. Direct immunofluorescent studies will characteristically show a positive lupus band test of all isotypes (ie, a full house immunoglobulin pattern) along with extensive decoration of keratinocytes for immunoglobulin G and complement reflective of the presence of antibodies to Ro.
Case 3 — B
Anti-epiligrin pemphigoid
The biopsy findings are characteristic of anti-epiligrin pemphigoid. In a minority of cases, the biopsy will show a neutrophil rich subepidermal blistering dermatosis reminiscent of other subepidermal blistering dermatoses, such as bullous systemic lupus erythematosus, linear IgA disease, P200 pemphigoid and inflammatory epidermolysis bullosa acquisita, a finding well-exemplified by this case.
In Panel B, there are linear deposits of immunoglobulin G (IgG) demonstrating dermal localization within the epidermal basement membrane zone. Circulating IgG antibodies react with the dermal side of a saline induced split skin devoid in collagen VII, and circulating IgG antibodies to laminin 5 detected by immunoblotting or immunoprecipitation. In Panel C, an indirect immunofluorescent assay is conducted utilizing patient’s serum and skin devoid in type VII collagen, a positive result is identified because immunoreactivity is not dependent the type VII antigenic epitope. In Panel D, salt split skin studies performed on the patient’s skin biopsy shows localization of immunoreactivity to the floor of the saline induced split. The antibody activity is against laminin 5, which also falls under alternative names including laminin 332, epiligrin, calanin and nicien. The actual molecular composition of laminin 5 is one comprising a heterodimer defined by 3 distinct chains designated alpha 3, beta 3 and gamma 2, respectively. The vast majority of patients who have this form of cicatricial pemphigoid have antibodies against the alpha 3 subunit. The association of anti-epiligrin pemphigoid with underlying malignancy may be related to the expression of laminin 5 by certain types of malignancies. Its high mortality reflects the underlying high-grade malignancy and immunosuppressive sequelae of iatrogenic drug therapy.
Case 4 — D
Vesicular mycosis fungoides
Although the diagnosis was obscured by vesiculation, there are important clues pointing to the correct diagnosis. In all cases, a very atypical, cerebriform, epitheliotropic, lymphocytic infiltrate was present. The intraepidermal lymphoid atypia characteristically exceeds that noted in the epidermis. The background architectural disposition of basilar colonization of the epidermis by atypical lymphocytes is a fairly ubiquitous finding. When one considers a conventional eczematous dermatitis, this pattern of passive interface dermatitis is not a feature. However, the most important clue is the mucinous quality of the vesicles essentially recapitulating follicular mucinosis. The abnormal lymphoid populace is of the CD4 (Panel C) subset exhibiting striking reductions in the expression of CD7 (Panel D) typical for plaque stage mycosis fungoides.
There are 6 prior cases of vesicular mycosis fungoides reported in the literature. In those cases exhibiting vesicular both clinically and histologically, the clinical course has been aggressive. Three of the 6 cases reported in the literature demonstrated lymph node involvement. In our experience, we have encountered 4 similar cases of which 2 of the cases have exhibited lymph node involvement.
The basis of the vesiculation could be reflective of a Th2 dominant cytokine microenvironment analogous to that seen in the setting of atopic eczema. It is well-established that conversion from a Th1 dominant microenvironment to one associated with a Th2 profile correlates with a more aggressive clinical course in the setting of mycosis fungoides, and hence could explain the association between vesicular mycosis fungoides and a more aggressive clinical course.
Dr. Magro is the director of dermatopathology at the Weill CornellMedical College in Manhattan NY, and is board certified in anatomic pathology, dermatopathology and cytopathology.
Dr. Magro is an expert in the diagnosis of complex inflammatory skin diseases. Her areas of expertise include cutaneous manifestations of autoimmune disease, systemic viral disease and vasculitis, atypical drug reactions, benign, atypical and overtly malignant lymphocytic infiltrates of the skin and diagnostically difficult melanocytic proliferations.
For more information, please visit www.weillcornelldermpath.com.
Disclosure: The author reports no relevant financial relationships.
