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Extraordinary Case Report

Sarcomatoid Variant of Primary Cutaneous Anaplastic Large Cell Lymphoma

Natsuaki, Yohei MD, PhD*; Muto, Ikko MD*; Kawamura, Miyuki MD*; Saruta, Hiroshi MD, PhD*; Teye, Kwesi PhD; Ohshima, Koichi MD, PhD; Nakama, Takekuni MD, PhD*; Ohata, Chika MD, PhD*

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The American Journal of Dermatopathology: December 2019 - Volume 41 - Issue 12 - p e164–e167
doi: 10.1097/DAD.0000000000001483
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Abstract

INTRODUCTION

Sarcomatoid anaplastic large cell lymphoma (ALCL) is rare, and most of the previously reported cases were primary systemic ALCL, some of which had cutaneous involvement.1,2 Only 3 cases of primary cutaneous sarcomatoid ALCL have been reported previously.3–5 Cutaneous ALCL is usually anaplastic lymphoma kinase (ALK)–negative, and ALK-positive ALCL is considered a systemic disease.6,7 Here, we report a new case of cutaneous sarcomatoid ALCL, which demonstrated spontaneous regression in the early disease course.

CASE REPORT

A 30-year-old woman presented to a gynecologist with a red nodule on the left groin with fever. Because an inflamed cyst was suspected, an incision was performed. However, it was not an inflammatory lesion but a mass. Therefore, a biopsy was conducted that revealed an unusual inflammatory and fibromyxoid tumor. Soon after the biopsy, the patient developed red plaques on other skin areas. Then, the patient was referred to our hospital. The patient had a medical history of chronic urticaria. Physical examination revealed 4 × 1-cm red nodule with central ulcer on the left groin (Fig. 1A). In addition, several red nodules or plaques, some of which had central ulcer, were observed on the back, both groins, left forearm, and left axilla (Fig. 1B). A new biopsy from the left groin revealed infiltration of spindle cells in the dermis with highly myxoid and vascular background (Fig. 2A). In addition to spindle cells, stellate-shaped cells were occasionally observed, and both types of cells had large atypical nuclei (Fig. 2B). Many neutrophils were admixed with these cells. Furthermore, reactive lymphocytes infiltrated in the deep dermis. Immunohistochemically, the spindle cells were positive for CD4, CD30, MIC2 (CD99), and epithelial membrane antigen (Figs. 2C–F) and negative for CD3, CD8, CD20, T-cell intracytoplasmic antigen-1, granzyme B, and ALK. Then, most of the skin lesions spontaneously resolved, but only a red nodule on the left axilla progressively expanded to the infraclavicular area during the following 2 months. A biopsy from the left axilla revealed a combination of CD30-positive spindle and round cells with occasional atypical multinucleated cells in the myxoid background (Fig. 2G). In addition, neutrophils also infiltrated in the lesion, but less as compared to the biopsy specimen taken from the left groin. Immunohistochemical profiles were the same as those of the previous biopsy (Figs. 2H, I). Although positron emission tomography and computed tomography revealed a large mass from the left axilla to the infraclavicular area, there was no apparent lymph node involvement. Bone marrow aspiration revealed normocellular bone marrow, and T-cell receptor rearrangement was not confirmed in either skin lesion or bone marrow. The patient was diagnosed with sarcomatoid variant of primary cutaneous ALCL. Finally, the patient received chemotherapy with 6 courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), which resulted in complete remission. Eighteen months have passed without relapses.

FIGURE 1
FIGURE 1:
A, Clinical manifestation of a red nodule with central ulcer on the left groin. B, Two crusted red nodules on the left forearm.
FIGURE 2
FIGURE 2:
A–F, A biopsy specimen from the left groin. A, A highly myxoid and vascular area was observed in the upper dermis (hematoxylin & eosin [H&E] ×20). B, In the highly myxoid and vascular area, in addition to many neutrophils, spindle cells and occasional stellate-shaped cells with large atypical nuclei were observed (H&E ×400). Atypical spindle cells were positive for CD4 (C), CD30 (D), MIC2 (E), and EMA (F) (C–F, ×400). G–I, A biopsy specimen from the left axilla. G, In the less myxoid background, spindle and stellate cells as well as round cells were observed with neutrophils (H&E ×400). Atypical spindle and round cells were positive for CD4 (H) and CD30 (I) (H, I, ×400).

DISCUSSION

Only 3 cases of primary cutaneous sarcomatoid ALCL have been reported to date.3–5 The first case was a 45-year-old man with skin lesion on the lower part of his right leg.3 Initially, the lesion was believed to be infective; however, incision and drainage did not improve the lesion. Then, a biopsy was performed, but because of sarcomatoid histological features with a myxoid stroma, high-grade sarcoma was misdiagnosed. The correct diagnosis of ALCL was made based on the following biopsy of one of the lymph nodes, which enlarged after local excision and postoperative radiotherapy of the skin lesion. However, the patient died of infection soon. The second case was a 68-year-old woman with 2 skin lesions on the back.4 Owing to the predominance of spindle over round cells in a myxoid stroma, several dermatologists and hematopathologists shared the impression of sarcoma. Immunohistochemistry revealed CD3, CD4, and CD30 positivity and CD8 and ALK-1 negativity of the tumor cells, resulting in the diagnosis of sarcomatoid ALCL. The patient had no systemic involvement, and the 2 skin lesions regressed without treatment. The third case was a 30-year-old woman with several painful ulcerated nodules on the right lower limb.5 Initially, the lesion was believed to be infective; however, empirical treatment was not effective. A biopsy of a nodule revealed fascicles of plump spindle-shaped cells in the diffuse mucoid degeneration of interstitial tissue in the dermis and the subcutis. The spindle cells were positive for CD4, CD5, CD30, EMA, TIA-1, GrB, and ALK but negative for CD3, CD15, CD20, CD8, CD56, CD68, SMA, and desmin. The patient had no systemic involvement. The diagnosis of cutaneous sarcomatoid ALK-positive ALCL was made. Although the patient achieved complete remission with chemotherapy, the lesions recurred in a short while. The tumors spread to the right upper limb and abdomen despite additional chemotherapy. The patient died of severe infection.

The previous 3 cases of cutaneous sarcomatoid ALCL shared the feature of atypical spindle cells and myxoid background with our case. Although the first and the second cases showed a storiform pattern, our case did not show it.3,4 We consider it was because of highly myxoid change in the left groin lesion and less spindle cell proportion in the left axilla lesion in our case, compared with the first and the second cases. The third case also did not show a storiform pattern despite lack of highly myxoid change.5 The scanning view of the biopsy specimen of the third case was reminiscent of septal panniculitis.

According to the recent review of sarcomatoid ALCL, MIC2 (CD99) was not tested in this category.8 However, frequent expression of CD99 in ALCL has been reported.9 In primary cutaneous ALCL, 64% of cases were positive for CD99. Our case demonstrated that sarcomatoid variant could also show CD99 positivity.

Our case was suspected with an inflammatory lesion at first, and lymphoma was not suspected because of the fibromyxoid nature in the initial biopsy. The first and the third previous cases and our case highlight that the clinical presentation of primary cutaneous sarcomatoid ALCL may mimic inflammatory skin lesions. In fact, it is hard to suspect lymphoma when the initial lesion is solitary.

The second previous case and our case demonstrated spontaneous regression. Although spontaneous regression of primary cutaneous ALCL occasionally occurs, relapse is common.6 In our case, despite regression of most lesions, the lesion in the left axilla expanded and required chemotherapy. However, the prognosis of primary cutaneous ALCL is usually excellent with 10-year disease-related survival rates exceeding 95%, and most cases are controlled by local radiotherapy.6 Skin relapses after chemotherapy often occur, but they do not show an aggressive clinical behavior.6 To the contrary, the clinical course of the third previous case, in which ALK was positive, was aggressive.5 ALK-positive primary cutaneous ALCL is rare and characterized by more aggressive clinical features than classic primary cutaneous ALCL, in which ALK is negative.10–13 Sarcomatoid feature does not seem to be related to the particular clinical course, but ALK positivity or negativity seems to be associated with prognosis regardless of histopathological variation.

Recently, Fernandez-Flores et al reported 2 cases of myxoid variant of primary cutaneous ALCL.14 According to them, myxoid variant is extremely rare, and their cases were the first reported cases.14 In those cases, tumoral cells were large atypical lymphocytes with hyperchromatic nuclei and prominent nucleoli, which were not considered as sarcomatoid. Although the authors did not describe the morphology of the tumoral cells in the details, it seemed to us that the figures showed some spindle cells among roundish atypical cells. Thus, myxoid primary cutaneous ALCL may be a close variant to primary cutaneous sarcomatoid ALCL.

Because the present case had multiple regressed lesions, the most important differential diagnosis was lymphomatoid papulosis (LyP). Primary cutaneous ALCL and LyP, both of which are primary cutaneous CD30+ lymphoproliferative disorders, share expression of CD30 antigen as a common immunophenotypic hallmark and exhibit an excellent prognosis but differ in regard to their clinical presentation.15 LyP is characterized by a chronic course of years to decades of recurrent papulonodular lesions, each of which undergoes spontaneous regression after weeks or months. Although 1 case of LyP with atypical CD30+ spindle cells was reported,16 spindle-cell/sarcomatoid variant is extremely rare in LyP. Primary cutaneous ALCL manifests in most patients with a solitary or grouped, rapidly growing and ulcerating large tumors or thick plaques. Rarely, the disease manifests with multifocal lesions. Spontaneous complete or partial regression of the tumors was reported in up to 44% of the patients.6,17 The large size of the lesions in the present case was more typical of ALCL.

In summary, our case and the previous 3 cases presented a difficulty in suspecting lymphoma only by the hematoxylin and eosin–stained sections, particularly when the lesion is solitary. Suspecting lymphoma even in a sarcomatoid solitary lesion is essential. Immunohistochemical studies are necessary to reach a correct diagnosis of sarcomatoid ALCL.

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Keywords:

sarcomatoid; anaplastic large cell lymphoma; cutaneous

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