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Year : 2022  |  Volume : 24  |  Issue : 3  |  Page : 114-116

Diagnostic Dilemmas in Cutaneous Pseudolymphomas

1 Department of Pathology, Armed Forces Medical College, Pune, Maharashtra, India
2 Dermatology and Venerology, Armed Forces Medical College, Pune, Maharashtra, India

Date of Submission31-Mar-2021
Date of Decision26-May-2021
Date of Acceptance04-Jun-2021
Date of Web Publication21-Jan-2022

Correspondence Address:
Lt Col (Dr) Puneet Baveja
Department of Pathology, Armed Forces Medical College, Pune, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jmms.jmms_47_21

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Cutaneous pseudolymphoma (CPL) is an umbrella term encompassing reactive lymphoproliferation that imitates cutaneous lymphomas clinically and/or histopathologically. We present the case of an elderly male presenting with solitary, painless, raised, and progressive swelling on the right side of the face of 9-month duration. Examination revealed a solitary, raised, slightly erythematous nodule without any surface changes. Clinically, the neoplastic differentials were given precedence owing to rapid onset and age at presentation. The nodule was excised in toto and, following histopathological examination and immunohistochemistry (IHC), diagnosed as CPL. We elaborate how pseudolymphomas can mimic lymphoma and can be distinguished only with an integrated clinical, histomorphological approach and the use of ancillary techniques including IHC.

Keywords: Cutaneous lymphoma, cutaneous pseudolymphoma, lymphoproliferative disorders

How to cite this article:
Paliwal G, Gopal A, Baveja P, Neema S. Diagnostic Dilemmas in Cutaneous Pseudolymphomas. J Mar Med Soc 2022;24, Suppl S1:114-6

How to cite this URL:
Paliwal G, Gopal A, Baveja P, Neema S. Diagnostic Dilemmas in Cutaneous Pseudolymphomas. J Mar Med Soc [serial online] 2022 [cited 2022 Sep 25];24, Suppl S1:114-6. Available from: https://www.marinemedicalsociety.in/text.asp?2022/24/3/114/336195

  Introduction Top

The process of accumulation of lymphocytes in the skin in response to a variety of known and unknown stimuli is collectively termed cutaneous pseudolymphoma (CPL).[1] It is usually a diagnosis of exclusion and can be classified on the basis of predominant immunophenotype as T-cell, B-cell, or mixed pseudolymphomas.[2] The histopathology of CPL is similar to variety of reactive and neoplastic lesions, hence clinical features and ancillary techniques assist in reaching a diagnosis.

Here, we present the case of a 78-year-old male presenting with a solitary progressive nodule on the right side of the face, its varied clinical possibilities, which turned out to be reactive lymphoproliferation.

  Case Report Top

A 78-year-old male presented to a tertiary care hospital in January 2021 with a painless, raised swelling on the right cheek noticed 9 months back, which had increased from initial size of <0.5 cm to present size of around 1.5 cm × 1.5 cm [Figure 1]a. The patient was a known case of primary hypertension and was on regular antihypertensives for the last 12 years. There was no history of any other drug intake. There was no history of any trauma or insect bite. The family history was noncontributory. The patient has not taken any treatment for the swelling.
Figure 1: (a) Nodular lesion of the left side of the face, (b) Dermal top-heavy diffuse infiltrate (H and E), (c) Subepidermal grenz zone (×40) (H and E), (d) Infiltrative. Ill circumscribed margin in deep dermis (×40) (H and E), (e) Subepidermal grenz zone with focal epidermotropism inset (×100) (H and E), (f) Mixed population of small-medium sized lymphoid cells and few histiocytes (×400) (H and E)

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On examination, a solitary, raised, firm nodule was present on the right cheek. It was not tender, slightly erythematous, with no evident surface changes. Dermoscopic examination revealed multiple arborizing vessels. The laboratory investigations including hemogram and biochemical parameters were within normal limits.

In view of the age profile and progressive nature of the nodule, the patient underwent wide local excision of the nodule with the clinical possibilities of nodular basal cell carcinoma, amelanotic melanoma, keratoacanthoma, trichoblastoma, and Merkel cell carcinoma.

The specimen received on gross examination revealed a skin covered tissue mass which included subcutaneous fat, measuring 4.5 cm × 2 cm × 1.2 cm, with a central nodular lesion measuring 1.4 cm × 1.4 cm × 0.7 cm. The cut surface of the nodule was homogeneous, firm, and white in color. All the four shave margins were processed separately.

Microscopic examination revealed a tissue lined by keratinized squamous epithelium with atrophic changes over the lesion. The lesion was located in the superficial dermis extending into the deeper dermis indicating a top-heavy lesion [Figure 1]b. A subepidermal grenz zone was evident with focal areas of epidermotropism and folliculotropism [Figure 1]c, [Figure 1]d, [Figure 1]e. It was composed of small- and medium-sized lymphoid cells having scant cytoplasm, round hyperchromatic nuclei, regular nuclear membrane, and inconspicuous nucleoli [Figure 1]f. Many intermixed plasma cells, histiocytes, and blood vessels were noted along with occasional eosinophils. Deeper adipose tissue was unremarkable. No spongiosis, Pautrier microabscess, or cerebriform nuclei were noted. The margins were free of the heavy diffuse infiltrate seen in the nodule.

On immunohistochemistry (IHC), the lymphoid cells showed diffuse positivity for CD45RA, CD45RO, CD3, CD2, CD5, CD8, and CD7. Focal positivity was seen for CD20, CD4, and CD68. The cells were negative for pan-cytokeratin (CK), CD30, ALK1, CD56, and synaptophysin. Mib-1 proliferation index was 20%–30% [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d, [Figure 2]e, [Figure 2]f.
Figure 2: Immunohistochemistry (×100): (a) CD45 positive in lymphoid cells, (b) These lymphoid cells are positive for CD3, (c) CD20 is positive in scattered b cells, (d and e) CD8-positive cells >CD4-positive cells, respectively, (f) Focal CD68 positive

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On the basis of histomorphology and IHC, a diagnosis of cutaneous T-cell lymphoid hyperplasia/pseudolymphoma was given.

  Discussion Top

CPL was first described under the term sarcomatosis cutis by Kaposi in 1891, and in 1967, Lever introduced the term pseudolymphoma of Spiegler and Fendt.[1],[3] With the passing time, more entities were added to the category of pseudolymphomas with a wide variety of causes, broadly divided into infectious, drugs, and foreign agents.[4] The exact incidence of this entity remains unknown.[5],[6] Pseudolymphomas have been classified according to the predominating immunophenotype (T-cell, B-cell, or mixed), the histopathological growth pattern, the etiology, or distinct clinical features.[4] Further, the cutaneous T-cell lymphomas (CTCLs) are divided into band-like pattern and nodular pattern, with B-cell lymphomas showing a nodular pattern.[5] Mitteldorf and Kempf have proposed to classify CPL into four main groups based on histopathological features and clinical data, namely nodular pseudolymphomas, pseudolymphomas as simulators of mycosis fungoides (MFs) and of other CTCLs, intravascular pseudolymphomas, and other pseudolymphomas.[7] These classifications help to shape an approach to tackle such cases and include a combination of histopathology (including IHC and molecular diagnostics), clinical presentation, and a further molecular workup, if necessary.

In our case, a diffuse pattern was identified on histomorphology with cells of small-to-medium size constituting the top-heavy dermal infiltrate. A possible diagnosis was still far at this juncture as both CTCL and pseudolymphomas have small-to-medium-sized cells. However, the presence of subepidermal grenz zone favored a B-cell CL. The morphological features pointing away from B-cell CL were lack of nodular architecture, focal epidermotropism, and folliculotropism. These features are found in MF which is a common CTCL and accounts for 50% of primary cutaneous lymphomas.[8] However, the absence of lymphocytes lining up along the dermoepidermal junction, the absence of Pautrier microabscess, and cerebriform nuclei convincingly ruled out MF and Sezary syndrome (SS) just on the basis of morphology. Further, the clinical features of history of 9 months, with gradual progression and localized nature of lesion, were against that of CTCL. Few variants of CTCL, like folliculotropic MF, also have an indolent course, and thus, ancillary studies were warranted further to clinical and morphological findings.

The characteristic basaloid cells with scant cytoplasm and peripheral palisading, peritumoral clefting, and mucinous stroma of basal cell carcinoma were absent. Trichoblastoma was also ruled out. The absence of keratin and atypical squamous cells also ruled out the possibility of keratoacanthoma. The cells were negative for pan-CK. The absence of nuclear clefting and neuroendocrine features ruled out Merkel cell carcinoma which was further confirmed by negative synaptophysin. Absence of prominent nucleoli, pigment and high mitotic index, supported by negative S-100 IHC assisted in ruling out the differential diagnosis of malignant melanoma.

IHC in our case showed the lymphoid cells to be positive for T-cell markers including CD3, CD2, CD5, CD8, and CD7 with focal cells positive for CD20, CD4, and CD68. The retained expression of CD3, CD7, and CD8> CD4 was confirmed against MF and SS.

The IHC features of CD8, CD3, and CD68 positivity and morphological profile of nonepidermotropic dense dermal infiltrates of small-to-medium-sized atypical lymphocytes along with clinically indolent course were guiding the diagnosis toward CD8+ acral T-cell lymphoma (CD8+), a provisional CTCL entity, which has been newly listed in the revised WHO classification 2017.[9] However, we were not able to exclude it for the want of transient ischemic attack-1 IHC and other ancillary studies including T-cell receptor gene rearrangement studies.

Treatment of pseudolymphoma is directed by the etiology and can vary from surgical excision to antibiotic therapy and stopping further exposure to inciting agent which was not evident in the instant case. Second-line therapy includes psoralen plus ultraviolet A therapy, 5-aminolevulinic acid photodynamic therapy, topical tacrolimus, topical imiquimod, and hydroxychloroquine sulfate.[4] Even after surgical excision, a watchful follow-up is imperative as CPL can progress to malignant lymphoma. The patient has been advised regular follow-up.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Kerl H. Inflammatory diseases that simulate lymphomas: Cutaneous pseudolymphomas. In: Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg IM, Austen KF, editors. Dermatology in General Medicine. New York: McGraw-Hill; 1993. p. 1315-27.  Back to cited text no. 1
Rijlaarsdam JU, Willemze R. Cutaneous pseudolymphomas: Classification and differential diagnosis. Semin Dermatol 1994;13:187-96.  Back to cited text no. 2
Bluefarb SM, editor. Lymphocytoma cutis. In: Cutaneous Manifestations of the Benign Inflammatory Reticuloses. Springfield (IL): Charles C Thomas; 1960. p. 131-99.  Back to cited text no. 3
Miguel D, Peckruhn M, Elsner P. Treatment of cutaneous pseudolymphoma: A systematic review. Acta Derm Venereol 2018;98:310-7.  Back to cited text no. 4
Ploysangam T, Breneman DL, Mutasim DF. Cutaneous pseudolymphomas. J Am Acad Dermatol 1998;38:877-95.  Back to cited text no. 5
Cerroni L. Pseudolymphoma, Cutaneous. In: Massi D, editors. Dermatopathology. Encyclopedia of Pathology. Switzwerland: SpringerNature; 2016. p. 277.  Back to cited text no. 6
Mitteldorf C, Kempf W. Cutaneous pseudolymphoma – A review on the spectrum and a proposal for a new classification. J Cutan Pathol 2020;47:76-97.  Back to cited text no. 7
Willemze R, Cerroni L, Kempf W, Berti E, Facchetti F, Swerdlow SH, et al. The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood 2019;133:1703-14.  Back to cited text no. 8
Petrella T, Maubec E, Cornillet-Lefebvre P, Willemze R, Pluot M, Durlach A, et al. Indolent CD8-positive lymphoid proliferation of the ear: A distinct primary cutaneous T-cell lymphoma? Am J Surg Pathol 2007;31:1887-92.  Back to cited text no. 9


  [Figure 1], [Figure 2]


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