The spectrum of CD30 positive lymphoproliferative disorders encompasses lymphomatoid papulosis (LYP),
primary cutaneous and secondary CD30+ve anaplastic large cell lymphoma (ALCL), borderline CD30 positive
lymphoproliferative disorder, Hodgkin's disease (HD) either primarily or secondarily involving the skin,
mycosis fungoides (MF) with large cell transformation, CD30+ve large B cell lymphoma and CD30+ve
lymphomatoid drug reactions. In one study that addressed the spectrum of CD30 positive cutaneous
lymphoproliferative lesions, ALCL comprised 45% of cases, LYP 17% of cases, borderline lesions 16% of
cases, non-Hodgkin's lymphoma of the nonanaplastic subtype 20% and HD 1% of cases (Paulli). This likely
represents a form of selection bias, however, as a study from MCP Hahnemann University, New York
University, and the University of California, San Francisco over a 3 year period showed ALCL to represent
a mere 0.9% of newly registered cutaneous lymphoma patients, while 13% of patients had LYP, 3% had
peripheral T-cell lymphoma, 4% had B-cell lymphoma, and the overwhelming majority represented mycosis
fungoides/Sezary syndrome (80%) (Zackheim). Lymphomatoid hypersensitivity reactions in the context of
persistent arthropod bite reactions, cutaneous herpes and paramyxovirus infection and chemotherapy and
other drug reactions may manifest reactive CD30 positive lymphoid infiltrates.
The diverse spectrum of cutaneous lesions associated with CD30 expression reflects the nature of the
CD30 molecule and the inherent diversity of cells in which it can be expressed including mitotically
active cells of monocytic, B cell or T cell lineage. The expression of CD30 does not equate with a
neoplastic event and can be identified in a minority of reactive T or B lymphocytes and in lymphocytes
exposed to transforming viruses such as Epstein Barr virus (EBV) and HTLV1. It was first detected on
Reed-Sternberg (RS) cells of HD but has since been described in stimulated or transformed peripheral
blood T or B cells, T cell and B cell lymphoma lines, and myeloid cell lines. In paraffin embedded
tissue, an epitope of the CD30 molecule which is preserved following formalin fixation is detected with
the BerH2 antibody; Ki-1, a monoclonal antibody raised against an HD cell line in 1982, is an antibody
which detects a much greater proportion of the CD30 molecule on frozen tissue and hence is a more
sensitive assay for CD30 expression. Ki-1 was subsequently shown to be expressed by a minority of small
lymphoid cells found in the parafollicular regions of normal lymph nodes. The Ki-1 antigen, now
designated the CD30 cluster, is part of the tumor necrosis factor family. The gene encoding the CD30
molecule is found on chromosome 1p36 .
LYMPHOMATOID PAPULOSIS (LYP)
First described by McCauley in 1968, LYP is a distinctive syndrome characterized by recrudescent eruption
of nodules or papules which clinically follow a benign course despite a worrisome histology. Clinical
criteria currently used to diagnose LYP are 1. Multiple papules or nodules; 2. Spontaneous regression or
waxing and waning of lesions that often heal with a scar; 3. No evidence that skin lesions progressively
grow to a diameter larger than 3 cm during 3 months of observation without treatment; and 4. Absence of
lymphadenopathy. Many articles suggest that 10 to 20% of cases manifest concurrent or subsequent
development of lymphomas include mycosis fungoides, anaplastic Ki-1 lymphoma, and Hodgkin's disease.
Recent reports indicate the actuarial cumulative risk approaches 80%. Lesions manifest no sex
predilection (Kadin) and can occur at any age from infancy to the eighth decade (Wang) with the median
age being in the fourth or fifth decades (Wang, Kadin). The incidence ranges from 1.2 - 1.9 per million
in New England (Wang). The overall prognosis in those patients who have LYP and then develop lymphoma
relates to the presence or absence of extracutaneous disease; those patients with extracutaneous disease
have a worse prognosis. Willemze first recognized two distinct variants: type A and type B. Those
patients who have or subsequently develop MF usually have type B LYP while those patients with CD30
positive lymphoma or Hodgkin's disease have type A LYP (Beljaards). It appears that progression of
lymphomatoid papulosis to malignant lymphoma is a more frequent occurrence in males (Beljaards).
The histology of LYP depends upon the age of the lesion biopsied (Kadin). Early lesions show only a
sparse, non-descript perivascular lymphoid infiltrate, while the characteristic atypical morphology is
seen in the fully-developed, mature lesion. With respect to the latter, two distinct morphologies are
described as "type A" and "type B" lesions (Willemze). The former comprise wedge-shaped superficial and
deep perivascular infiltrates which include both small lymphoid forms and atypical large lymphocytes
mimicking Reed-Sternberg cells and their variants. At a light microscopic level both variants show a
prominent angiocentric mononuclear cell infiltrate which expands the vessel wall with resultant luminal
attenuation. Ischemic alterations of the overlying epidermis may be seen. Mural or luminal fibrin
deposition is not observed. There is concomitant erythrocyte extravasation within the dermis and
epidermis. In the type A lesion the dominant cell around and within the vessel walls is a large
lymphoreticular cell in the 20 to 30 micron range with abundant lightly staining cytoplasm; the cells
have round, oval and or reniform nuclei with an open chromatin pattern and a prominent basophilic
nucleolus. Most of the cells are mononuclear although occasional binucleated forms can be seen. In some
cases there is hypereosinophilia of the cytoplasm with senescent alteration of the nucleus resulting in a
morphology reminiscent of the mummified cell encountered in Hodgkin's disease. Mitoses are numerous.
There is a polymorphous inflammatory background comprising eosinophils and neutrophils with
leukocytoclasia. The infiltrate extends deep and can expand the adventitial dermis of the eccrine coil
and pilosebaceous unit. Epidermotropism is minimal to absent. Fully-developed type A lesions of two or
three weeks' age frequently contain numerous histiocytes, neutrophils and eosinophils, with the
granulocyte component forming sheets in the superficial dermis and frequently manifesting exocytosis,
eventuating in epidermal necrosis, ulceration and formation of a neutrophil-containing scale-crust
(Willemze). Neutrophils may pack the blood vessels; fibrinoid necrosis and erythrocyte extravasation
may be seen (Willemze) and fibrosis may result. The so-called "type B" lesions mimic MF histologically,
with band-like infiltrates of small, irregularly-contoured lymphoid forms in close apposition to the
undersurface of the epidermis. Pautrier's micro-abscesses are unusual in both types of lesion and their
presence should raise consideration of MF. The so-called "type C" lesion shows nodules of CD30+ve cells
cognate to anaplastic large cell lymphoma but sparing the subcutis.
Phenotypic and molecular studies
Lymphomatoid papulosis is a lymphoproliferative disorder. A study of patients with LYP uncomplicated
by lymphoma showed through PCR amplification that a single Vβ-7 transcript of identical size was
present in each lesion in the majority. When the dominant band from each excised lesion was removed from
the gel, reamplified and directly sequenced, it was confirmed that monoclonality from multiple lesions of
patients with LYP is derived from a single transformed T cell. This study also showed via the method of
semiquantitative PCR and DNA sequencing that the atypical lymphocytes in lesions of LYP and lymphoma were
Immunophenotypically most large atypical lymphocytes of types A and B LYP exhibit pan T cell and
T-helper antigen expression (ie CD3,4+5). Both the large atypical cells of type A LYP and the large
cerebriform cells of type B LYP express activation markers HLADR, TAC (the antigen for the interleukin-2
receptor), transferrin receptor (T9) and Ki-67. Phenotypic abnormality is revealed in both subtypes of
LYP by virtue of diminished expression of the pan T cell antigens Leu-1 and/or CD7/Leu-9. The cells show
variable Ki1 expression but are frequently –ve in type B LYP.
Methotrexate (MTX) appears to the treatment of choice for more severe cases of LYP. The effectiveness
of MTX relates to its inhibitory effect on DNA synthesis, anti-inflammatory effects or both. The
atypical lymphocytes seen in LYP and Ki1 lymphoma manifest a high mitotic activity and hence it would
seem likely that methotrexate significantly inhibits the proliferation of these cells especially during
the initial phase of lesional development. The recommended dosage is 10 to 25 mg every 1 to 4 weeks.
The major side effect is hepatic fibrosis; liver biopsies with treatment guidelines similar to those used
for psoriasis patients should be employed.
BORDERLINE CD30 POSITIVE LYMPHOPROLIFERATIVE DISORDERS
There are cases that manifest borderline morphologic features between ALCL and LYP, with lesions
clinically compatible with the latter. The hallmarks light microscopically include a cohesive growth of
atypical cells in the depths of the lesion however more superficially the infiltrate of atypical cells is
arranged in small clusters and as well there are numerous admixed inflammatory cells including
granulocytes. The absolute distinction between ALCL and LYP can be difficult, prompting a diagnosis of
borderline C30+ve lymphoproliferative disease.
ANAPLASTIC Ki1 LYMPHOMA
At the other end of the spectrum of CD30 positive lymphoproliferative disorders is Ki-1 positive
lymphoma. Stein and coworkers in 1985 recognized a distinctive large cell hematopoietic neoplasm
associated with extensive lymph node effacement manifesting sinusoidal accentuation. The neoplastic cell
population is typically of T-cell or null-cell phenotype. There is heterogeneity in terms of the
morphologic spectrum of the lesion with cells ranging from small forms to large highly atypical
sarcomatoid variants. There are four main variants: the common type (classic), giant cell-rich or
pleomorphic, small cell, and lymphohistiocytic or Hodgkin's disease-like. There are other unusual
variants including neutrophil rich, eosinophil rich, sarcomatoid, and signet ring. Although one
recognizes these morphologic variants, there is no clear cut clinical difference between the various
subtypes except with respect to the small cell variant which often has a leukemic picture (Kinney) and a
more aggressive clinical course. An alternative classification scheme reflects anaplastic lymphoma
kinase (ALK) expression; specifically the lymphomas are categorized according to the presence or absence
of ALK. The vast majority of primary cutaneous ALCL's are ALK-ve; ALK–ve tumors tend to occur in older
individuals and have a much worse than do ALK+ve forms.
CD30+ve ALCL in the skin may represent a primary cutaneous lymphoma, may represent secondary
involvement in the setting of primary nodal Ki1 positive lymphoma, or may develop in the setting of
another form of lymphoma, specifically Hodgkin's disease, MF, and other forms of post thymic T cell
lymphoma (Kinney). Primary cutaneous ALCL arises denovo in the skin with
the median age of presentation being 60 years. Lesions usually present as solitary tumors manifesting
variable ulceration but may exhibit multicentricity. Approximately 25% of patients with ALCL showed
lesional regression. The absolute distinction between ALCL and LYP may be difficult, but in LYP the
lesions are multiple, small, and have a tendency for spontaneous regression; extracutaneous spread does
not occur. In contrast in primary cutaneous ALCL the lesions may be solitary, may not regress and may
manifest extracutaneous dissemination. Secondary ALCL may arise in the progression of other lymphomas
including peripheral T cell lymphoma, Hodgkin's disease, MF and LYP. The acquisition of CD30 expression
in a previously CD 30-ve lymphoma is considered a poor prognostic sign.
Some authors note that the presence of a solitary lesion greater than 3 centimeters, persistence
without spontaneous regression, and the presence of significant lymphadenopathy probably indicate
malignant lymphoma and/or progression of lesions of LYP into ALCL. Such criteria might be construed as
rather stringent in that there are published series addressing the clinical features of ALCL with lesions
smaller than 2 centimeters and where only 63% had a solitary lesion while the remainder had multiple
lesions. Others have used a 2 centimeter cut off as distinguishing lymphoma from LYP. Regression is
only marginally helpful as it may be seen in both conditions (Demieere). The cases that most frequently
undergo regression are the so-called borderline cases which are those which manifest overlap features
between CD30 positive lymphoma and LYP.
Molecular basis of anaplastic Ki-1 lymphoma
The pathogenetic basis of the regression is of interest. The question arises as to what molecular
events are responsible for the spontaneous regression of some cases of CD30 positive lymphoma and what
events lead to lesional progression eventuating in death. A transforming growth factor (TGF)-β
receptor designated TBRII is a multifunctional polypeptide which regulates cell proliferation and
differentiation; its main effect is one of growth inhibition. Cell culture lines derived from a lesion
of Ki1+ve lymphoma did not show an inhibitory growth response to TGFβ. The basis was a point
mutation in TBRII, leading to inhibition of the wild-type receptor and hence rendering the cell resistant
to the inhibitory effects of TBRII (Knaus).
Lymph node based CD30+ve large cell lymphomas of either T cell or null cell lineage manifest a
characteristic translocation, namely t(2;5)(p23;q35) and express the NPM-ALK hybrid protein detected by
the antibody ALK1. This distinctive translocation was first described in 1989. Five years later the
translocation site was cloned by Morris et al and it was shown that the chromosomal rearrangement fuses
part of the nucelophosmin gene on chromosome 5q35 to a portion of the ALK gene on chromosome 2p23
generating a chimeric molecule and a unique 80-kDa NPM ALK fusion protein. The incidence of this
translocation ranges from 15% to 80% of cases of ALCL in the hands of different authors. The
translocation has been detected in some peripheral T-cell lymphomas other than classical Ki1+ve ALCL and
in some diffuse large cell B cell lymphomas. In addition a cryptic abnormality has been detected that is
easily recognized using fluorescence in situ hybridization : inv (2)(p23q35). The result is distinctive
ALK protein expression restricted to the cytoplasm of the neoplastic cells. ALK protein expression is
held to be an independent positive prognostic variable based upon retrospective analyses (Kinney and
Kadin, 1999). The principle methods of detection of ALK are through RT in situ PCR, cytogenetics, and
Expression of ALK is seen in a small minority of cases of LYP and primary CD30+ve ALCL (i.e. less than
10% of cases) with several studies not detecting its presence in any cases. In contrast the rate of
t(2:5) is higher in lymph node-based CD30+ve lymphomas with a prevalence of about 40%. There is a
suggestion that the t(2:5) may be more common in cutaneous lesions derived from younger patients. The
findings suggest that lymph node based CD30+ve lymphoproliferative disease is distinct from its cutaneous
There are five distinct histomorphologic forms of ALCL (Kinney and Kadin, 1999). Most common in our
hands are the pleomorphic variant, comprising large cells with wreath-like giant cells, and the
monomorphic variant comprising sheets of monotypic medium or large cells. The lymphohistiocytic variant
has numerous admixed reactive histiocytes. The small cell variant shows scattered large atypical cells
as described above, but the dominant cell is a small to intermediate sized lymphocyte that demonstrates
nuclear contour irregularities including the presence of polylobate or floret-like forms; the cells have
clear cytoplasms and distinct cytoplasmic membranes. Sarcomatoid and signet ring variants of ALCL are
rare. There are two cytologic lymphocyte types that ought to prompt recognition of Ki1+ve ALCL
(Demierre). Type I cells are polygonal forms between 10 and 30 microns in diameter and exhibit a
distinct pink-staining cell membrane. Their angulated cell borders imparts a squamoid appearance to the
cell. The nuclei are usually round to oval but can show irregular foldings. The chromatin is dispersed
as coarse clumps, associated with large areas of clearing. Nucleoli are large and multiple. The
cytoplasm is abundant and is pale to lightly amphophilic in quality. The type II cell is monomorphous,
measuring 15 to 50 microns in diameter with a round to oval, lobulated, reniform or horseshoe shaped
nucleus that may be centrally placed with a prominent paranuclear hof. The chromatin is irregularly
clumped and shows less clearing than the type I cell. The cytoplasm is abundant and deeply amphophilic
or basophilic. The cells may contain multiple nuclei, oftentimes in a wreath like arrangement and/or
resembling those cells encountered in HD.
Pathologically CD30-positive lymphoma differs from LYP by virtue of a predominance of CD30 positive
cells with greater than 75% of cells having a large anaplastic morphology. In contrast, in LYP the CD30
positive cells are noted amidst a dominant polymorphous inflammatory cell background. Features
suggestive of evolution from LYP into CD30 positive lymphoma include a further loss of pan T cell marker
expression, extension into the subcutis and a greater proportion of atypical cells relative to the
inflammatory cell background with focal effacement of the dermal architecture by sheets of atypical
cells. In addition to the sheet like pattern of growth there is striking angiocentricity.
Pseudoepitheliomatous hyperplasia occurs in 20 to 30% of all cases of CD30+ve ALCL; the presence of this
phenomenon in lesions of LYP has not been previously reported (Scarisrick et al).
Most cases of Ki1+ve lymphoma exhibit a T cell or null cell phenotype, with a small minority having a
B cell phenotype. The basis of their classification as ALCL is due to co-expression of CD30, EMA, and
the demonstration of a t(2;5) translocation. However, the B cell variant, clearly representing the least
frequent of the immunophenotypic subgroups, is prognostically similar to other forms of large cell B cell
lymphoma. The expression of activation antigens is very common including T9, HLA-DR, and Tac. They may
show an aberrant T cell phenotype by virtue of CD3 negativity. Unlike Hodgkin's disease the cells are
CD45 positive and are Leu-M1 (CD15) negative. In addition, there is evidence of cytotoxic potential. In
nodal Ki1 positive lymphomas, the cytotoxic characteristics are revealed by virtue of the presence of
cytotoxic cell associated antigens including CD8, CD56, CD57, and the cytotoxic granular proteins
perforin and T-cell restricted intracellular antigen-1 (TIA-1), the latter a 15-kDa cytotoxic granule
associated membrane protein expressed in natural killer cells and cytotoxic T-lymphocytes that was first
characterized by Anderson et al in 1990 and that reacts with 20-36% of peripheral blood T-lymphocytes,
being strongly expressed by NK cells and CD8+ cytolytic T-cells and less strongly by CD4+ve cells. Since
then several studies have shown that the expression of these cytotoxic proteins are seen in a spectrum of
lymphoma including NK-cell lymphomas, rare cases of Hodgkin's lymphoma, Ki1+ve ALCL and certain
distinctive forms of peripheral T cell lymphoma including subcutaneous T cell lymphoma, hepatosplenic,
and intestinal lymphoma. In primary cutaneous Ki1+ve ALCL's granzyme B and TIA's have been observed
while in CD30-ve primary cutaneous large T-cell lymphomas the neoplastic cells usually do not express
these proteins (Kumar).
In the small cell variant, the smaller lymphoid cells are typically CD30 negative nevertheless there
is a clonal loss of one of the pan-T cell antigens especially CD3 and as well expression of the NPM-ALK
protein may be seen. In those cases of null phenotype expression of CD11b and CD13 has been observed
(Simonitsch). ALK positivity is seen in only 15% and 30% of the Hodgkin like and giant cell forms
respectively while ALK positivity is seen in 80 to 100% of classic small cell and lymphohistiocytic
In those null-cell ALCL's gene rearrangement studies nevertheless do demonstrate a rearrangement of
the T cell β-receptor (Foss) and even in these lymphomas there is expression of various cytotoxic
proteins including granyme, perforin, and TIA-1. It would appear that a certain percentage of these
tumors also may represent true NK cells in light of the expression of the NK cell associated marker CD56
in some cases of ALCL in concert with the failure to detect TCR gene rearrangements.
PRIMARY CUTANEOUS HODGKIN'S DISEASE
Although exceptional cases of primary cutaneous Hodgkin's disease (HD) occur, most cases of cutaneous HD
represent secondary involvement; even this is a rare event in patients with advanced disease. In most
instances the skin lesions represent a direct extension from extensive mediastinal disease. To diagnose
primary cutaneous HD there must be no evidence of extracutaneous HD at 6 months follow-up.
Histologically there is a background infiltrate of small mature lymphocytes producing a morphology
reminiscent of benign reactive lymphoid hyperplasia as seen in lesions of lymphocytoma cutis, but with
scattered Reed Sternberg (RS) like cells present that demonstrate the typical CD30+ve/CD15+ve/CD45-ve
phenotype. Some patients may have disease limited to the skin while others may develop nodal HD several
years after the initial cutaneous presentation.
Lymphocyte rich classic HD is a form of CD30+ve HD with two recognized variants: a diffuse and a
nodular form. The nodular form has also fallen under the alternative appellation of follicular HD. The
classic appearance is one of expanded follicles composed predominantly of mantle zone lymphocytes in the
absence of sclerosis. Within the expanded mantle zones are scattered RS cells and their variants; the
diagnosis is suspected due to the presence of these scattered RS cells in a benign-appearing follicle.
Prognostically lymphocyte rich forms of classical HD likely do better than either mixed cellularity or
nodular sclerosing variants. The histology closely resemble nodular lymphocyte predominant HD.
The molecular and phenotypic profile for HD is characteristic; specifically the RS like cells are
typically of B cell derivation. Occasionally a null phenotype exists; less than 2% of cases are of T
cell derivation. The RS cells are typically EMA-ve despite expression of CD30 and CD15.
PRIMARY CUTANEOUS CD30 POSITIVE T CELL RICH B CELL LYMPHOMA
We have encountered patients with CD30+ve 10CBCL. In one patient presenting with a
solitary scalp nodule there was an ensuing indolent course with no recurrence following complete removal.
In the other case in whom the morphology was dominated by sheets of transformed cells, the lesions were
multiple; the follow up in this case is only a matter of weeks and to date we are not aware of
extracutaneous disease in this patient. The diagnosis was difficult as the neoplastic component was
obscured by the reactive inflammatory infiltrate. Integral to the diagnosis was a high level of
suspicion based on the clinical presentation in concert with the morphologic identification of a minor
cell populace which demonstrated morphologic features that one associates with a CD30 positive
lymphoproliferative disease. Specifically, the cells manifested large eosinophilic multilobate or
irregularly notched nuclei; the traditional round, oval and regular undulating contours manifested by
transformed reactive cells were not encountered. Phenotypically the cells resembled a marginal zone
phenotype by virtue of being CD20+ve and CD10-ve with co-expression of CD43 along with CD23 and CD5
negativity. The differential diagnosis of the inflammatory cell rich case was primarily with primary
cutaneous HD however the co-expression of CD45 and the absence of CD15 expression did not support this
diagnosis. A form of extracutaneous CD30 positive large B cell lymphoma dominated by sheets of
transformed cells has been previously described and is to be distinguished from both Ki1+ve ALCL and HD;
prognostically they behave no differently than other forms of large B cell lymphoma. In the one
multicenter study on cutaneous CD30 positive lymphoproliferative disease only 2 out of 17 cases in the
CD30 positive non-Hodgkin's disease category were of B cell phenotype. The cells had a polymorphic
centroblastic morphology and or/ had a hybrid morphology including immunoblasts, centroblast-like cells
and RS-like cells comprising the dominant infiltrate. These uncommon lymphomas were designated as CD30
positive non-anaplastic large cell B cell lymphomas.
LYMPHOMATOID CD30+VE DRUG REACTIONS
We have encountered cases of lymphomatoid drug eruptions in which a significant number of CD30 +ve
lymphocytes was observed, mainly in a perivascular array. In particular, 5 of 15 cases of lymphomatoid
drug reaction, all showing clonal rearrangement of TCR- g, manifested CD30+ve large cells in the dermis
(Magro et al., 2003). These drug-associated atypical cutaneous lymphoid proliferations manifested
heterogenous clinical presentations included papular dermatitis, purpuric lesions, infiltrative plaques
resembling MF and erythroderma. Light microscopically, the lesions manifested lymphoid atypia which
assumed angiocentric, lichenoid or eczematous patterns, interstitial granulomatous inflammation, or
atypical pigmentary purpura, all patterns previously described in drug associated cutaneous lymphomatoid
hypersensitivity reactions (Magro + Crowson, 1997; Crowson et al., 1999; Crowson + Magro, 2002) .
The implicated drug classes were those previously associated with lymphomatoid drug reactions,
including minocycline and its analog erythromycin, ACE inhibitors, antidepressants, anticonvulsants,
antihistamines, anti-hypertensive blocking agents including b-blockers, calcium channel blockers, lipid
lowering agents, and a-antagonists In vitro studies have shown depression
of T-cell function with antihistamines, b -blockers, antidepressants, lipid lowering agents, sex steroid
related drugs, and calcium channel blockers.
Most cases demonstrated histological features useful in the distinction of lymphomatoid
hypersensitivity from malignant lymphoma including directed migration of lymphocytes into suprapapillary
plates, a site of preferential antigenic processing, eosinophilic spongiosis, papillary dermal edema and
the presence of intraepidermal lymphocytes which were less atypical than those in the dermis. Cases of
MF can manifest one or more of the aforesaid features and not all of these features are seen in every
case of lymphomatoid hypersensitivity. Although the light microscopic overlap between lesions of MF and
drug induced lymphomatoid hypersensitivity suggests that phenotypic and genotypic analyses would be
logical diagnostic adjuncts, in this study those analyses suggested MF over a reactive process, and were
In MF and other forms of post thymic CTCL, the neoplastic cells are of T cell lineage, and typically
express CD2, CD3, CD4 and CD5. The T-helper (Th) lineage of the neoplastic lymphocytes is suggested by
virtue of a CD4/8 ratio which exceeds 4:1 and by CD4 expression by cytologically atypical cells. In our
CD30+ve lymphomatoid drug reactions, most cases studied showed a CD4/8 ratio which exceeded 4:1. In a
few cases the intraepidermal lymphoid population was predominated by CD8 positive lymphocytes while the
dermal lymphocytes mainly expressed CD4, findings characteristic of a type IV immune reaction with
combined delayed type hypersensitivity and cellular cytotoxic features. This differential localization
of CD8 and CD4 lymphocytes to the epidermis and dermis, while characteristic of a reactive process, was
only present in a minority of cases.
The neoplastic lymphocytes of MF often manifest deletions of the pan T cell markers CD7 and CD62 K.
Therefore, CD7 and CD62 K expression in less than 50% of an infiltrate has been held to indicate MF; the
greater the diminution of expression, the more specific is the finding. As CD62 K is only demonstrable
in frozen tissue and there is rarely a deletion of CD2 and CD5 in lesions of MF, the lack of CD7
expression has been held by some authors to be an important phenotypic indicator of CTCL. However, 16 of
19 biopsies in our recent series exhibited reduced CD7 expression in only 50% or less of the infiltrate.
The number of T cells expressing CD7 was 30% or less in 5 cases, a profile indistinguishable from CTCL.
In 2 cases, there was also a significant reduction in CD62 K expression. Although the aforementioned
pattern of pan T cell marker deletion could be construed as being compatible with MF, there are
subpopulations of reactive T lymphocytes which do not express CD7 or CD62 K, including memory T-cells.
The expression of CD7 and CD62 K by lymphocytes correlates inversely with HLADR expression. CD62 K or
L-selectin is a member of a group whose cluster designations are CD62 K, CD62 E (E-selectin), and CD62 P
(P-selectin). L-selectin is expressed on blood monocytes, blood neutrophils, subsets of natural killer
cells and T and B lymphocytes including those of naïve phenotype, but not cells of Th1 memory subtype,
and is shed from the surface of activated leukocytes. Hence T lymphocytes lacking both CD7 and CD62 K
would be expected in type IV antigen driven inflammatory processes.
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