|Year : 2015 | Volume
| Issue : 3 | Page : 656
A rare case of ALK negative CD30+ primary cutaneous anaplastic large cell lymphoma in a young adult
HB Sridevi1, PR Shanthala2, CV Raghuveer2, Ananth K Prabhu3, Jallaluddin K. C. Akbar3, GS Shivaprasad3, Pooja K Suresh1, Sanjay Navani4
1 Department of Pathology, Kasturba Medical College, Mangalore, Manipal University, Manipal, India
2 Department of Pathology, Yenepoya Medical College, Yenepoya University, Mangalore, India
3 Department of Surgery, Yenepoya Medical College, Yenepoya University, Mangalore, India
4 Department of Pathology, Surgical Pathologist and Immunochemist, Lab Surgpath, The Human Protien Atlas (HPA) Project, Mumbai, Maharashtra, India
|Date of Web Publication||9-Oct-2015|
H B Sridevi
Department of Pathology, Kasturba Medical College, Mangalore, Manipal University, Manipal - 575 001, Karnataka
Source of Support: None, Conflict of Interest: None
Cutaneous anaplastic large cell lymphoma can present either as a primary disease or as secondary to a pre-existing systemic anaplastic lymphoma. Distinguishing primary cutaneous anaplastic lymphoma (PC-ALCL) from its systemic counterpart requires a complete clinical and laboratory workup. We hereby report a case of PC-ALCL in a young adult, who presented with unusual rapidly progressive ulcerated mass in the neck. Biopsy showed anaplastic large cells, which were strongly positive for CD30 and CD25 but ALK1 gene product was negative. Clinical examination and computed tomography (CT) scan ruled out extracutaneous involvement. Chemotherapy with 6 cycles of CHOP regimen was planned and on follow-up, a complete remission of the lesion was attained.
Keywords: Anaplastic lymphoma kinase, aggressive, CD30, chemotherapy, primary cutaneous anaplastic large cell lymphoma
|How to cite this article:|
Sridevi H B, Shanthala P R, Raghuveer C V, Prabhu AK, Akbar JK, Shivaprasad G S, Suresh PK, Navani S. A rare case of ALK negative CD30+ primary cutaneous anaplastic large cell lymphoma in a young adult. J Can Res Ther 2015;11:656
|How to cite this URL:|
Sridevi H B, Shanthala P R, Raghuveer C V, Prabhu AK, Akbar JK, Shivaprasad G S, Suresh PK, Navani S. A rare case of ALK negative CD30+ primary cutaneous anaplastic large cell lymphoma in a young adult. J Can Res Ther [serial online] 2015 [cited 2020 Jul 16];11:656. Available from: http://www.cancerjournal.net/text.asp?2015/11/3/656/139338
| > Introduction|| |
Primary cutaneous anaplastic large-cell lymphoma (PC-ALCL) is the second most common cutaneous T-cell lymphoma.  In the 2008, WHO classification, PC-ALCL is categorized under primary cutaneous CD30-positive T-cell lymphoproliferative disorders along with lymphomatoid papulosis.  PC-ALCL remains confined to the skin with rare dissemination beyond local lymph nodes in most cases.  PC-ALCL must be distinguished from secondary cutaneous lesions of systemic ALCL since the latter runs a poor clinical course.  PC-ALCL mainly affects older patients in the sixth decade, although it has rarely been described in the young adults. ,, We hereby report a case of unusually aggressive PC-ALCL in a young adult.
| > Case report|| |
An 18-year-old boy presented with a right sided, 2 × 3 cm tender, ulcerated neck swelling of two months duration. The mass rapidly increased to 8 × 8 cm with pain and bleeding [[Figure 1]a; ulcerated swelling in the right side of neck lifting the ear lobe] extending from right post-auricular region below the mandible up to the midline of neck. There was no significant organomegaly or any other skin lesions or lymphadenopathy. There was no history suggesting towards lymphomatoid papulosis that generally presents with multiple grouped self-healing rhythmical paradoxical erythematous papules or nodules that spontaneously regresses. There was also absence of scar and hyperpigmentation.
|Figure 1: Primary Cutaneous Anaplastic Large Cell Lymphoma. (a) Ulcerated swelling in the right side of neck lifting the ear lobe. (b) Axial view of CT scan neck with a heterogeneously enhancing mass in the neck extending laterally from the skin and compressing the internal jugular vein medially|
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Ultrasound abdomen and chest X-ray were normal. The CT scan revealed a heterogeneously enhancing mass in the neck extending laterally from the skin and medially compressing the internal jugular vein and causing effacement of the right parapharyngeal and carotid spaces [[Figure 1]b; Axial view of CT scan neck with a heterogeneously enhancing mass in the neck extending from the skin and involving up to the midline (arrow)]. Routine blood counts and urine investigations examination were within normal limits. Serum lactate dehydrogenase (LDH) was raised. Liver and renal function tests were normal. HBsAg and HIV tests were non-reactive.
Histopathology showed marked ulceration and necrosis of skin with a tumor composed of dense sheets and nodular aggregates of pleomorphic large cells exhibiting tendency of discohesion separated by an edematous, inflamed stroma [[Figure 2]a; Confluent sheets and nodular aggregates of anaplastic large cells (H and E, ×100). Inset: Markedly ulcerated and necrosed skin (H and E, ×40)]. The tumor cells had the characteristic morphology of anaplastic cells, showing round, oval and irregularly lobated nuclei, multiple prominent nucleoli and abundant eosinophilic cytoplasm; few Reed-Sternberg (RS)-like cells were also noted [[Figure 2]b; Anaplastic cells with reniform nuclei and prominent nucleoli. Inset: RS-like cell (H and E, ×400)]. High mitotic activity, both typical and atypical forms were observed (Six/HPF). Large areas of necrosis with an exuberant inflammatory infiltrate of neutrophils and histiocytes were present. Skin adnexal structures were completely destroyed.
|Figure 2: Histopathology and immunohistochemistry of PC-ALCL. (a) Confluent sheets and nodular aggregates of anaplastic large cells (H&E, ×100). Inset: Markedly ulcerated and necrosed skin (H&E, ×40). (b) Anaplastic cells with irregular lobated nuclei and prominent nucleoli. Inset: RS like cell (H&E,×400). (c and d) Anaplastic cells strongly positive for CD30 and CD25. (e) ALK1 negativity in tumor cells. (f) High Ki67 proliferative index. (IHC, ×400)|
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Immunohistochemistry (IHC) revealed more than 75% of large atypical cells showing CD30 membrane and golgi region positivity and membrane positivity for CD25 [[Figure 2]c and d; Anaplastic cells strongly positive for CD30 and CD25 (IHC, ×400)]. However, anaplastic lymphoma kinase (ALK) 1 was negative [[Figure 2]e; ALK1 negativity in tumor cells (IHC, ×400)]. LCA, CD 20, PAX5, CD2, CD3, CD4, CD5, CD45RO, epithelial membrane antigen (EMA) and myogenin were also negative. The Ki67 proliferative index was very high and was expressed by majority (95%) of neoplastic cells [[Figure 2]f; High Ki67 proliferative index (IHC, ×400)]. Thereby, with the morphological findings, immunohistochemical workup and by absence of clinical signs of systemic involvement, the diagnosis of primary cutaneous anaplastic large cell lymphoma was made.
Patient received six cycles of chemotherapy with a combination of vincristine (1 mg), doxorubicin (30 mg), cyclophosphomide (500 mg) and prednisolone. The response to treatment has been remarkable with complete disappearance of the swelling [[Figure 3]; Remission of swelling with scar formation following chemotherapy]. The patient has been advised follow-up on a monthly basis for the first 4-6 months, and once in 2 months for the next six months. After one year, depending on the patient's response, the frequency of the follow-up can be once in 3 months or every six months. The patient does not have any evidence of relapse in the last 14 months.
|Figure 3: Remission of swelling with scar formation following chemotherapy|
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| > Discussion|| |
Primary Cutaneous T-cell lymphomas refer to clinically and biologically heterogenous group of non-Hodgkin's lymphomas (NHL) defined by clonal proliferation of cutaneous T lymphocytes.  PC-ALCL accounts for approximately 9% of all cutaneous T-cell lymphomas.  The criteria for the diagnosis of PC-ALCL includes - more than 75% of CD30 + large anaplastic cells in skin biopsy and absence of clinical history of lymphomatoid papulosis, mycosis fungoides or other cutaneous lymphomas along with absence of extracutaneous localization after extensive investigations at presentation.  Our patient fulfilled all the criteria for PC-ALCL.
PC-ALCL mostly occurs in elderly men as solitary asymptomatic reddish to violaceous nodule, plaque or tumor over the head, trunk and extremities. It is uncommon before the age of 20 and generally peaks in the sixth decade of life.  The lesions are often slow growing with an indolent clinical course and may present for a long time before being diagnosed.  In contrast, our patient was a young man of 18 years with a solitary swelling, which progressed rapidly in a very short duration complicated with bleeding from ulcer site.
PC-ALCL is characterized histologically by dense cohesive sheets of large atypical cells, known as "hallmark cells", comprising more than 75% of the cellular infiltrate. The cells have abundant cytoplasm with reniform-shaped hyperchromatic nuclei and prominent eosinophilic nucleoli with frequent mitoses;  similar histological findings were observed in our case.
PC-ALCL can be classified as T (CD3+), B (CD20+) or null (CD3-, CD20-) cell immunophenotype.  Our case was both CD3 and CD20 negative, and hence can be classified as null-cell type of PC-ALCL.
Tumour cells of all anaplastic large cells lymphomas either systemic or cutaneous types, strongly expresses CD30 on the cell membrane and Golgi bodies; hence presence of membrane associated CD30 expression is used for defining ALCL.  Nuclear matrix protein (NMP)-ALK is a nuclear fusion protein, which is not expressed in normal lymphocytes. ALK expression is common in systemic ALCL and rare in PC-ALCL; its expression in skin is a warning to look for systemic disease.  Systemic lymphomas and cutaneous involvement secondary to systemic ALCL usually expresses EMA.  Our case was CD30+, ALK- and EMA-. The above immunoprofile and absence of evidence of systemic involvement excluded the above possibilities.
Our patient was in T1bN0M0 stage, based on the TNM classification for primary cutaneous lymphomas other than mycosis fungoides/Sezary syndrome of the ISCL and EORTC.  Long-term follow-up is essential in all cases of PC-ALCL limited to localized disease, as extracutaneous dissemination can occur in approximately 10% of cases, particularly to the regional lymph nodes. 
PC-ALCLs are chemosensitive and radiosensitive with treatment options being surgical excision, radiotherapy and CHOP chemotherapy or combination of these.  Treatment of PC-ALCL should be decided according to the size and extent of the tumor. Surgical excision or radiotherapy can be the initial or first-line therapy for single or localized grouped lesions and chemotherapy with CHOP regimen can be limited to multifocal PC-ALCL. Surgical excision and radiotherapy when applied individually can achieve a complete remission rate of at least 95% as against 85% with CHOP regimen.  Even though surgical excision or radiotherapy remains the preferred mode of treating localized PC-ALCL; the cases with large tumor burden that are rapidly progressing or those with extracutaneous involvement can be treated with systemic chemotherapy.  In view of an aggressive clinical course, our patient was treated with chemotherapy and presently after completion of 6 cycles of CHOP, the tumor has disappeared completely. Alternative therapies such as low-dose methotrexate, which is generally non myelosuppressive, systemic retinoids, topical treatments with bexarotene (targretin) or nitrogen mustard (mustargen), Interferon-alpha (IFNα) or thalidomide may be used for treating PC-ALCL. , Relapse is common with any of treatment regimen, hence long term follow-up is required. 
| > Conclusion|| |
PC-ALCL is a diagnostic and therapeutic challenge, which requires a systematic multidisciplinary approach to rule out systemic ALCL or other forms of systemic lymphomas. The clinical presentations and histomorphology of both types are similar which adds to further diagnostic difficulties. Since PC-ALCLs have better prognosis compared to other lymphomas, rendering a definite diagnosis would be helpful in better patient management. Though, provisional diagnosis may be possible on light microscopy, the definite role of panel of IHC markers in making the final diagnosis is evident from the present case. Our case also enlightens about the variable clinical presentation of localized PC-ALCL in a young adult with an unusually aggressive clinical course that required systemic chemotherapy as first-line of treatment and thus cautions the clinicians to have high index of suspicion of such similar presentation.
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[Figure 1], [Figure 2], [Figure 3]