Case Studies

A 47 year old man developed wheezing and shortness of breath on mild exertion, as well as general malaise. These symptoms worsened over the course of 4 months, and chest radiographs were obtained. They demonstrated reticulonodular interstitial infiltrates throughout both lung fields.

In addition, thorough inspection of the skin showed nodular lesions of palpable purpura on the distal extremities.

Examination of the peripheral blood leukocytes revealed 34% eosinophils, and active urine sediment was present on urinalysis.

A skin biopsy was done.

DIAGNOSIS = CHURG-STRAUSS (ALLERGIC) GRANULOMATOSIS

Churg-Strauss Syndrome (CSS) is a systemic vasculitis, and it was first described in 1951 by Dr. Jacob Churg and Dr. Lotte Strauss. The syndrome they identified includes asthma, eosinophilia, fever, and accompanying vasculitis of various organ systems. CSS shares many clinical and pathological features with polyarteritis nodosa, but the latter disease lacks granulomas as well as tissue or peripheral blood eosinophilia. An alternative designation for CSS is that of Allergic granulomatosis.

Patients with CSS are usually middle aged, with a slight male predominance. They develop adult-onset or newly-worsened asthma and also may manifest signs and symptoms relating to other organ systems, including the skin. Nasal polyps and allergic rhinitis may be present as well. The overt phase of the disease is often marked by eosinophilia, as high as 60% in differential white blood cell counts.

The vasculitis of CSS potentially involves the skin, lungs, nerves, kidneys, and heart. A peculiar feature of this aspect of the disease is that of mononeuritis multiplex. Cutaneous manifestations usually take the form of deeply-seated vasculitic lesions, with fibrinoid necrosis of vessels walls, granulomatous inflammation, and intense eosinophilia with "flame figures."

Among all of the vasculitides, asthma is a distinctive feature of CSS. The particular combination of symptoms and signs, the pattern of organ involvement, and the presence of eosinophilia are singular for this disorder. In addition to a detailed history and physical examination, results of CBCs, chest radiographs, nerve conduction tests, and biopsies of the skin, upper airways, or skin are helpful diagnostically.

Treatment is based on the use of corticosteroids, with additional cytostatic medications and/or plasmapheresis. Durable remissions are obtained in approximately 65% of cases.

References

1. Guillevin L, Pagnoux C, Mouthon L: Churg-Strauss syndrome. Semin Respir Crit Care Med 2004; 25: 535-545.

2. Kawakami T, Soma Y, Kawasaki K, et al.: Initial cutaneous manifestations consistent with mononeuritis multiplex in Churg-Strauss syndrome. Arch Dermatol 2005; 141: 873-878.

3. 3. Diri E, Buscemi DM, Nugent KM: Churg-Strauss syndrome: diagnostic difficulties and pathogenesis. Am J Med Sci 2003; 325: 101-105.

4. 4. Solans R, Bosch JA, Perez-Bocanegra C, et al.: Churg-Strauss syndrome: outcome and long-term followup of 32 patients. Rheumatology 2001; 40: 763-771.

5. 5. Lee MW, Jang KA, Lim YS, et al.: Cutaneous extravascular necrotizing granulomas (Churg-Strauss granulomas). Clin Exp Dermatol 1999; 24: 193-195.

6. 6. Davis MD, Daoud MS, McEvoy MT, Su WPD: Cutaneous manifestations of Churg-Strauss syndrome: a clinicopathologic correlation. J Am Acad Dermatol 1997; 37: 199-203.

Case 2:

A 1 year old boy developed brownish-red macules and plaques over the trunk, which slowly enlarged. On physical examination, the lesions urticated when rubbed.

A biopsy was performed.

Chloroacetate esterase (von Leder's Stain) Immunostain for CD117 (c-kit)

DIAGNOSIS--- URTICARIA PIGMENTOSUM (MAST CELL DISEASE)

Urticaria pigmentosum (UP) is a cutaneous eruption caused by aggregations of mast cells in the dermis. Both adults and children are affected, but UP is typically seen in infancy. Indeed, some lesions may be present at birth.

The condition is reflected by the presence of small brown-red macules or papules, which itch, redden, and urticate after gentle rubbing (Darier's sign). These occur principally on the trunk. Sometimes, resolution leaves a residuum of melanin pigmentation.

Spontaneous improvement in UP usually occurs as the patient ages. Antihistamines may be helpful for symptom relief, and trauma should be avoided. Patients with UP may also benefit from the use of sodium cromoglycate, a mast-cell stabilizer.

Pathologically, one observes monomorphous infiltrates of oval to round cells throughout the dermis, surrounding adnexal structures. These may closely approximate the epidermal basement membrane, and pigment incontinence may be seen beneath it. Differential diagnosis centers on UP vs. Langerhans cell histiocytosis or melanocytic nevus. Histochemical staining for chloroacetate esterase, with the von Leder method, or imunopositivity for CD117 (c-kit protein) supports the diagnosis of UP.

References

1. Lazarus GS, Guzzo C, Lavker RM, Murphy GF, Schechter NM: Urticaria pigmentosum: nature’s experiment in mast cell biology. J Dermatol Sci 1991; 2: 395-401.

2. Akin C, Valent P, Escribano L: Urticaria pigmentosa and mastocytosis: the role of immunophenotyping in diagnosis and determining response to treatment. Curr Allergy Asthma Rep 2006; 6: 282-288.

Case 3:

A 41 year old man developed a slowly-growing plaque in the skin of the left thigh. When excised, it measured 4 cm in greatest dimension.

 CD34 Immunostain

Dx Dx=Cutaneous Solitary Fibrous Tumor

Over the last 15 years, it has become increasingly evident that the lesion now known as solitary fibrous tumor (SFT) is widely-distributed topographically. The pleura is the most common location for this lesion, but it has been reported in virtually all other body sites as well. SFT may be encountered in the superficial soft tissues or skin of the head and neck, trunk, and genitoperineal area. It ranges in size from 1 to 6 cm. in greatest dimension, and usually presents as a painless mass. Grossly , SFT of soft tissue is circumscribed but not encapsulated. It has a homogeneous, tan-gray, rubbery cut surface and is said by surgeons to “shell out." Histologically, one may encounter the patternless pattern of spindle-cell growth cited above in connection with GCA; alternatively, herringbone-like, storiform, undulating-neuroid, or densely cellular and mitotically-active growth patterns can be seen as well. However, there is typically no necrosis in subcutaneous lesions. The immunophenotypic profile of cutaneous & soft tissue SFT is like that seen in giant cell fibroblastoma, giant cell angiofibroma, or SFT of the pleural surfaces. Diffuse CD34-reactivity is the unifying feature, together with concurrent positivity for bcl-2 and CD99 in many instances. Superficial SFT only rarely recurs, and no metastases have been reported. Hence, it can be regarded as a borderline lesion for practical purposes.

REFERENCES

1: Cowper SE, Kilpatrick T, Proper S, Morgan MB. Solitary fibrous tumor of the skin. Am J Dermatopathol 1999; 21: 213-219.

2: Morgan MB, Smoller BR. Solitary fibrous tumors are immunophenotypically distinct from mesothelioma(s). J Cutan Pathol 2000; 27: 451-454.

3: Smith KJ, Skelton HG. Solitary fibrous tumor. Am J Dermatopathol 2001; 23: 81-82.

4: Sigel JE, Goldblum JR. Solitary fibrous tumor of the skin. Am J Dermatopathol 2001; 23: 275-278.

5: Hardisson D, Cuevas-Santos J, Contreras F. Solitary fibrous tumor of the skin. J Am Acad Dermatol 2002; 46 (2 Suppl): S37-S40.

6: Erdag G, Qureshi HS, Patterson JW, Wick MR. Solitary fibrous tumors of the skin: a clinicopathologic study of 10 cases and review of the literature. J Cutan Pathol 2007; 34: 844-850.