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Dermatopathology

Case 6 - T-cell Rich Angioma-like Polypoid Pseudolymphoma

Alexander Lazar


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Clinical History:
Female age 36 with an erythematous nodule on the shoulder present for "some months". The clinical assessment was possible pyogenic granuloma. The excised lesion was received in consultation with concern for a lymphomatous process. The lesion has not recurred during more than 6 years of follow-up and no additional lesions have been noted.


Case 6 - Slide 1
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Case 6 - Figure 1
The lesion is polypoid with a somewhat nodular infiltrate, 20x.
Case 6 - Figure 2
The infiltrate consists primarily of lymphocytes, 100x.
Case 6 - Figure 3
At most, minimal cytologic atypia is noted, 400x.

Case 6 - Figure 4
Very focal areas of necrosis and surrounding fibrosis are noted.
Case 6 - Figure 5 - CD3
The infiltrate consists primarily of CD3-positive T-cells, 40x.
Case 6 - Figure 6 - CD20
Nodules of CD20-positive B-cells are admixed, 100x.


Histologic Features:
The sections reveal a polypoid lesion with a nodular dermal infiltrate composed of lymphocytes admixed with small vessels. At most, minimal cytologic atypia was noted in the infiltrate. A focal area of necrosis with surrounding fibrosis was also seen.

Ancillary Studies:
Immunohistochemical studies revealed that the lymphocytic infiltrate consists primarily CD3-positive T cells with small nodules of CD20-positive B cells admixed. Both B- and T-cell gene re-arrangement studies revealed a polyclonal population.

Differential Diagnosis:
On the basis of the histologic and immunohistochemical images presented, the differential diagnosis would include:
  • Cutaneous lymphoma

  • Acral pseudolymphomatous angiokeratoma of children (APACHE)

  • Angiolymphoid hyperplasia with eosinophilia

  • Benign cutaneous lymphoid hyperplasia

  • Lobular capillary hemangioma / pyogenic granuloma

  • T-cell rich angioma-like polypoid pseudolymphoma

Diagnosis:
T-cell Rich Angioma-like Polypoid Pseudolymphoma

Discussion:
We believe that this case may represent a novel lesion that we have provisionally termed T-cell rich angioma-like polypoid pseudolymphoma. The most important point is that this lesion appears to behave in a benign fashion. We have accumulated 13 strikingly similar cases which will be discussed further below.

Cutaneous lymphoma:
The two primary cutaneous B-cell lymphomas that would be diagnostic considerations in this case would be follicular center lymphoma and marginal zone B-cell lymphoma in the WHO-EORTC classification [1]. This case lacks the expanded germinal centers of follicular lymphoma and the expanded marginal zone with lymphoplasmacytoid forms of marginal zone lymphoma. In addition, cytologic atypia is minimal and the B-cells constitute only a minority of the cells by immunohistochemistry. This case is not characteristic or particularly suggestive of any described form of T-cell lymphoma.

Acral pseudolymphomatous angiokeratoma of children (APACHE):
This lesion was originally described in 1988 as grouped angiomatous papules on acral sites with a keratotic surface or collar around the base, suggestive of angiokeratoma of Mibelli. [2, 3] It has also been described under a variety of suggested monikers including "small papular pseudolymphoma [4]," "acral angiokeratoma-like pseudolymphoma [4, 5], " "acral pseudolymphomatous angiokeratoma [3]," "papular angiolymphoid proliferation with epithelioid features in adults and children (PALEFACE) [6]," and "papular angiolymphoid hyperplasia [7]." Although APACHE was considered a vascular neoplasm initially, it is now considered a pseudolymphoma rather than an angiokeratoma. Immunohistochemical studies showed an admixture of B-and T-cells in varying proportions. Although, the present case shares many features of this entity, APACHE is described as multiple papules primarily in children (but may occur in adults on occasion), and is present at acral sites. The present case occured in an adult and on the shoulder.

Lobular capillary hemangioma / pyogenic granuloma:
This was primarily a clinical concern. The histologic features did not show a well-developed lobular capillary vascular proliferation characteristic of this entity [8].

Angiolymphoid hyperplasia with eosinophilia / epithelioid hemangioma (ALHE):
While there is a definite angiomatous/vascular component to this case, it lacks the characteristic plump endothelial cells of ALHE which are epithelioid in appearance and often have prominent cytoplasmic vacuoles. Instead, the vessels and endothelial cells of this case resemble the high endothelial venules of the paracortical area of the lymph nodes. The stromal cellular infiltrate of ALHEalso has prominent eosinophils and mast cells, which are absent in this case. Finally, ALHE is usually encountered in the head and neck region rather than the shoulder. [9]

Benign cutaneous lymphoid hyperplasia (BCLH):
BCLH is a diagnostic consideration. However, the polypoid nature of the present case, lack of germinal center formation and vascular pattern would be somewhat unusual for BCLH. A similar proliferation of small blood vessels is observed in the entity angioplasmocellular hyperplasia, [10] but the present case lacks endothelial cells with vacuolated cytoplasm and a predominance of plasma cells. [10]

We (Eduardo Calonje and myself) have now collected a series of 13 lesions with strikingly similar features to that presented above. While these lesions share features with APACHE, we believe them to be distinct. Since the original description of APACHE, an additional 23 histologically similar cases of this benign and non-progressive entity have been reported in the international literature, 18 of which conformed to the classical presentation described above. [2, 3, 4, 5, 6, 7, 11, 12, 13, 14, 15, 16, 17, 18] However, rare cases of APACHE are described as solitary lesions (n=3), [3, 6, 15] occurring in adults (n=6) [3, 4, 5, 12] and at non-acral sites (n=4). [3, 6, 15] The 3 described solitary cases [3, 6, 15] show striking clinical and histological resemblance to our collection of 13 cases, which we believe are dissimilar in terms of clinical presentation, but likely related to APACHE given the overlapping histologic features. This may imply that both entities belong to a wider spectrum of related lesions.

Our collected series of 13 cases includes 10 females and 3 males ranging in age from 16 to 71 (median, 41). Each presented as solitary polypoid erythematous papule ranging in size from 2.5 to 9 mm (mean, 7.5 mm). They occurred primarily from the trunk or head and neck regions. The majority were excised with a clinical impression of pyogenic granuloma, but were sent in consultation with concern for a lymphomatous process. All were treated by excision and none has recurred with median follow-up of 24 months indicating a benign nature.

References:
  1. Willemze R, Jaffe ES, Burg G, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. May 15 2005;105(10):3768-3785.

  2. Ramsay B, Dahl MGC, Malcom A, Wilson Jones E. Acral pseudolymphomatous angiokeratoma of children (APACHE). Br J Dermatol. 1988;119 ((Suppl 33)):13.

  3. Kaddu S, Cerroni L, Pilatti A, Soyer HP, Kerl H. Acral pseudolymphomatous angiokeratoma. A variant of the cutaneous pseudolymphomas. Am J Dermatopathol. Apr 1994;16(2):130-133.

  4. Okada M, Funayama M, Tanita M, Kudoh K, Aiba S, Tagami H. Acral angiokeratoma-like pseudolymphoma: one adolescent and two adults. J Am Acad Dermatol. Dec 2001;45(6 Suppl):S209-211.

  5. Ohtsuka T, Yamazaki S. Acral angiokeratoma-like pseudolymphoma in a 28-year-old Japanese woman. Dermatology. 2003;207(1):77-78.

  6. Fernandez-Figueras MT, Puig L. Of APACHEs and PALEFACEs. Am J Dermatopathol. Apr 1995;17(2):209-211.

  7. Okuda C, Ito K, Ito M. Acral pseudolymphomatous angiokeratoma of children: a case with a lesion on the wrist. Acta Derm Venereol. 2002;82(4):301-302.

  8. Patrice SJ, Wiss K, Mulliken JB. Pyogenic granuloma (lobular capillary hemangioma): a clinicopathologic study of 178 cases. Pediatr Dermatol. Dec 1991;8(4):267-276.

  9. Olsen TG, Helwig EB. Angiolymphoid hyperplasia with eosinophilia. A clinicopathologic study of 116 patients. J Am Acad Dermatol. May 1985;12(5 Pt 1):781-796.

  10. Gonzalez S, Molgo M. Primary cutaneous angioplasmocellular hyperplasia. Am J Dermatopathol. Jun 1995;17(3):307-311.

  11. Gansz B, Stander S, Metze D. [Acral pseudolymphomatous angiokeratoma of children (APACHE)]. Hautarzt. Mar 2005;56(3):270-272.

  12. Hagari Y, Hagari S, Kambe N, Kawaguchi T, Nakamoto S, Mihara M. Acral pseudolymphomatous angiokeratoma of children: immunohistochemical and clonal analyses of the infiltrating cells. J Cutan Pathol. May 2002;29(5):313-318.

  13. Hara M, Matsunaga J, Tagami H. Acral pseudolymphomatous angiokeratoma of children (APACHE): a case report and immunohistological study. Br J Dermatol. Apr 1991;124(4):387-388.

  14. Kim Y, Dawes-Higgs E, Mann S, Cook DK. Acral pseudolymphomatous angiokeratoma of children (APACHE). Australas J Dermatol. Aug 2005;46(3):177-180.

  15. Kiyohara T, Kumakiri M, Kawasaki T, Takeuchi A, Kuwahara H, Ueda T. Linear acral pseudolymphomatous angiokeratoma of children (APACHE): further evidence that APACHE is a cutaneous pseudolymphoma. J Am Acad Dermatol. Feb 2003;48(2 Suppl):S15-17.

  16. Lee MW, Choi JH, Sung KJ, Moon KC, Koh JK. Acral pseudolymphomatous angiokeratoma of children (APACHE). Pediatr Dermatol. Sep-Oct 2003;20(5):457-458.

  17. Lee MW, Lee DK, Choi JH, Moon KC, Koh JK. Clinicopathologic study of cutaneous pseudolymphomas. J Dermatol. Jul 2005;32(7):594-601.

  18. Murakami T, Ohtsuki M, Nakagawa H. Acral pseudolymphomatous angiokeratoma of children: a pseudolymphoma rather than an angiokeratoma. Br J Dermatol. Sep 2001;145(3):512-514.