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Alert Number 169

CLL and Skin Cancers: How to "Sell" Your Doctors

Date: June 18, 2006

After reading our last Alert dated June 16th, 2006, several subscribers to Alerts wrote and asked for specific published references regarding the risk of skin cancer (basal cell and squamous cell carcinoma) in CLL patients. For some patients, these references may be needed to get their oncologist and/or dermatologist to take their concerns seriously.

Fair enough, the good doctors need evidence, we shall give them evidence, by the boat-load. Below is a list of abstracts that I have collected over the past few years. The publication dates span from August 1979 to December 2005. All you have to do is read the titles of the abstracts. The take home message is clear:

  • CLL patients are more likely to run into skin cancer problems. This risk factor can be made worse by therapy, especially with T-cell depleting drugs.
  • Common BCC and SCC can be more dangerous in CLL patients, than in normal people.
  • Skin cancer issues may compromise your ability to deal with CLL and vice versa.
  • Catching skin cancer early and taking prompt action is your best bet of avoiding serious (and potentially life threatening) complications down the road.
  • By the way, squamous cell carcinoma can happen where the sun don't shine, such as inside of your mouth, lining of the lungs, uterus etc. There is not a whole lot you can do about the deep interior regions, but you surely can do something about getting examined for all the accessible regions, including the inside of your mouth, between your toes, soles of your feet etc. You get my drift.

Here is an email that I got this morning (name and email address withheld for confidentiality), from someone who knows what he is talking about:

Chaya--I am a dermatologist with CLL, and have been following your website for the last few years, and I commend your attention to the hazards of skin cancer in CLL patients. Readers should know now, that in addition to sun-block with high SPF, there are now many companies selling sun-block clothing, and these should be used along with repetitive sun-block application. One can find long sleeve shirts and long thin pants for swimming, golf, etc.

Keep up the great work!

With admiration for all of your efforts,

XXX

Please get this message out to others who may not be frequent visitors to this website. If you are an Opinion Leader and have your own website or discussion group, this is one Alert you have our permission to reproduce in full. You will be saving lives.

Be well,

Chaya
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Abstracts:

J Am Acad Dermatol. 2005 Dec;53(6):1067-71.

Increased metastasis and mortality from cutaneous squamous cell carcinoma in patients with chronic lymphocytic leukemia.

Mehrany K, Weenig RH, Lee KK, Pittelkow MR, Otley CC.

Department of Dermatology, Oregon Health Sciences University, Portland, Oregon.

In patients with chronic lymphocytic leukemia, squamous cell carcinoma behaves aggressively. Our purpose was to compare squamous cell carcinoma metastasis and mortality between patients with chronic lymphocytic leukemia and control subjects. Medical records were assessed retrospectively for 28 patients with chronic lymphocytic leukemia who underwent surgical excision of cutaneous squamous cell carcinoma and for 56 matched control subjects. The rate of metastasis and mortality from cutaneous squamous cell carcinoma were determined on a per-patient basis. Three of 28 patients with chronic lymphocytic leukemia had metastasis and died of metastatic disease. No metastases or deaths occurred among the 56 control subjects. Compared with control subjects, chronic lymphocytic leukemia patients with cutaneous squamous cell carcinoma were more likely to have metastasis (P = .0031) and die of metastasis (P = .0033). No significant association was detected between metastasis and history of chemotherapy administration for chronic lymphocytic leukemia. Among patients with chronic lymphocytic leukemia, surveillance for skin cancer and a decreased threshold for biopsy of suspect lesions are warranted.

PMID: 16310071 [PubMed - indexed for MEDLINE]
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Skinmed. 2005 Sep-Oct;4(5):300-4.

Cutaneous squamous cell carcinoma in patients with chronic lymphocytic leukemia.

Kaplan AL, Cook JL.

Department of Medicine (Dermatology), Duke University Medical Center, Durham, NC.

Patients with chronic lymphocytic leukemia are at heightened risk for the development of cutaneous mali gnancies, especially squamous cell carcinoma. These tumors portend a worse prognosis than is typically seen in immunocompetent patients. Patients with chronic lymphocytic leukemia who develop squamous cell carcinoma are more likely to develop multiple tumors, recurrences after treatment, and regional or distant spread of their tumor. Evaluation of the literature substantiates the ominous nature of squamous cell carcinoma in patients with underlying lymphocytic malignancies.

PMID: 16282752 [PubMed - indexed for MEDLINE]
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Leuk Lymphoma. 2005 Jul;46(7):1051-5.

Accelerated growth of skin carcinoma following fludarabine therapy for chronic lymphocytic leukemia.

Rashid K, Ng R, Mastan A, Sager D, Hirschman R.

Division of Hematology-Oncology, Cabrini Medical Center, NY

We present four patients with chronic lymphocytic leukemia treated with fludarabine, who developed aggressive skin cancer after years of quiescence, a short time after institution of treatment. Their leukemias responded well to therapy with fludarabine with initial treatment as well as relapse. Three patients had recurrence with basal cell carcinomas with multiple, rapidly growing tumors and one had recurrence of both basal and squamous cancers and eventually died of metastatic squamous cell carcinoma. Fludarabine induces prolonged period of lymphopenia, affecting especially the T cell population, which is crucial in the defense against skin cancers. There appears to be a direct association between fludarabine and the flare up of skin cancers in these patients, possibly analogous to the increased incidence of these malignancies in patients on chronic cyclosporine immunosuppression.

PMID: 16019557 [PubMed - indexed for MEDLINE]
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Dermatol Surg. 2005 Jan;31(1):38-42; discussion 42.

High recurrence rates of squamous cell carcinoma after Mohs' surgery in patients with chronic lymphocytic leukemia.

Mehrany K, Weenig RH, Pittelkow MR, Roenigk RK, Otley CC.

Department of Dermatology, Mayo Clinic, Roches ter, MN

BACKGROUND: Cutaneous cancers exhibit a much higher incidence in patients with chronic lymphocytic leukemia than in nonleukemic patients. Squamous and basal cell carcinomas also exhibit greater subclinical tumor extension in patients with chronic lymphocytic leukemia.
OBJECTIVE: The purpose of this study was to estimate and compare the recurrence rates of squamous cell carcinoma after Mohs' surgery in patients with chronic lymphocytic leukemia compared with those in controls and to evaluate differences among squamous cell carcinoma size and histologic grade.
METHODS: We retrospectively assessed the clinical histories, postoperative notes, and surgical photographs of patients with chronic lymphocytic leukemia and controls matched (2:1) for age, sex, and surgical year. Both patients and controls underwent Mohs' surgery for squamous cell carcinoma of the head and neck at the Mayo Clinic between March 1988 and April 1999.
RESULTS: Twenty-eight patients who underwent Mohs' surgery for 57 squamous cell carcinomas had 7 recurrences. The cumulative incidence of recurrence on a per-tumor basis was 4.3% at 1 year, 14.8% at 3 years, and 19.0% at 5 years. Squamous cell carcinoma was seven times more likely to recur in patients with chronic lymphocytic leukemia than in controls (p = .003). The distribution of tumor histologic grade was not significantly different between patients and controls (p = .39). Maximum preoperative tumor diameters were clinically similar between patients and controls (median 15 mm vs 14 mm; p = .04).
CONCLUSION: The recurrence rates of squamous cell carcinoma were significantly higher in patients with chronic lymphocytic leukemia. Squamous cell carcinomas in patients with chronic lymphocytic leukemia did not exhibit a significant difference in histologic grade or clinical difference in preoperative tumor size. Close surveillance for squamous cell carcinoma recurrence is warranted in patients with chronic lymphocytic leukemia.

PMID: 15720094 [PubMed - indexed for MEDLINE]
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Arch Dermatol. 2004 Aug;140(8):985-8.

High recurrence rates of Basal cell carcinoma after mohs surgery in patients with chronic lymphocytic leukemia.

Mehrany K, Weenig RH, Pittelkow MR, Roenigk RK, Otley CC.

Department of Dermatology, Mayo Clinic, Rochester, MN

OBJECTIVES: To estimate and compare the recurrence rates of basal cell carcinoma (BCC) after Mohs surgery in patients with chronic lymphocytic leukemia (CLL) and controls and to evaluate differences among histologic subtypes of BCC.
DESIGN: Retrospective assessment of clinical histories, postoperative notes, and surgical photographs.
SETTING: Tertiary-care institution (Mayo Clinic, Rochester, Minn).
PATIENTS: Twenty-four patients with CLL who underwent Mohs surgery for 33 BCCs and 66 controls matched for sex, age, and surgical year who underwent Mohs surgery for BCC of the head and neck from May 1988 through September 1998.
RESULTS: Among the 24 patients with CLL who underwent Mohs surgery for 33 BCCs, there were 4 recurrences. The cumulative incidence of recurrence on a per-tumor basis was 3% at 1 year, 12% at 3 years, and 22% at 5 years. Basal cell carcinoma was 14 times more likely to recur in patients with CLL than in controls (P =.02). Overall, there were no significant differences between patients with CLL and controls in preoperative tumor size (median, 1.6 cm vs 1.4 cm; P =.18) and proportion of aggressive histologic subtypes of BCC (58% vs 41%; P =.12).
CONCLUSIONS: Recurrence rates of BCC are significantly higher after Mohs surgery in patients with CLL. Overall, patients with CLL do not appear to have significantly larger BCCs or more aggressive histologic subtypes of BCC. In patients with CLL, close surveillance is warranted for recurrence of BCC and a decreased threshold is indicated for subsequent biopsies.

PMID: 15313816 [PubMed - indexed for MEDLINE]
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Br J Dermatol. 2004 Jun;150(6):1129-35.

Cutaneous findings in chronic lymphocytic leukaemia.

Agnew KL, Ruchlemer R, Catovsky D, Matutes E, Bunker CB.

Department of Dermatology The Royal Marsden Hospital, London SW3 6JJ, U.K.

BACKGROUND: Chronic lymphocytic leukaemia (CLL) is a malignancy characterized by clonal expansion of B lymphocytes with distinct morphology and immunophenotype. The dermatological literature relating to CLL is sparse. A global descriptive survey of a large number of CLL patients has not previously been published.
OBJECTIVES: To report the spectrum of dermatological conditions seen in a large series of CLL patients.
METHODS: Skin complications in patients with established CLL were identified retrospectively from clinical and photographic records, principally a database of over 750 consecutive cases. These events were classified, enumerated and compared.
RESULTS: Forty patients with 125 skin manifestations were identified and studied. Forty-one manifestations had documented clinical or histological atypia. In 21 of these 41 complications there had been no prior immunosuppressive therapy. We observed that cutaneous malignancies frequently presented atypically both clinically and histologically. There were 18 patients with 56 instances of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), and clinical atypia was more common with SCC than with BCC. Other cutaneous findings included varicella zoster (n = 6), leukaemia cutis (n = 3), acute graft-versus-host disease (n = 5), cutaneous drug eruptions (n = 9), multiple warts (n = 3), herpes simplex (n = 3), cutaneous T-cell lymphoma (n = 2), eosinophilic folliculitis (n = 2), malignant melanoma (n = 2) and Merkel cell tumour (n = 2).
CONCLUSIONS: We have identified a range of dermatological conditions in CLL patients, with a tendency to atypical presentations. The atypia was independent of prior chemotherapy.

PMID: 15214899 [PubMed - indexed for MEDLINE]
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Dermatol Surg. 2003 Jul;29(7):769-71.

A diagnosis of chronic lymphocytic leukemia prompted by cutaneous lymphocytic infiltrates present in mohs micrographic surgery frozen sections.

Padgett JK, Parlette HL 3rd, English JC 3rd.

Department of Dermatology, University of Virginia, Charlottesville, VA

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the United States. Patients with CLL are at an increased risk for the development of second malignant neoplasms, the most common of which is cuta-neous squamous cell carcinoma (SCC). Cutaneous infiltrates of CLL have been reported in association with primary cutaneous neoplasms, including SCC, basal cell carcinoma, and actinic keratosis. The finding of a dense lymphocytic infiltrate surrounding a cutaneous neoplasm should prompt consideration of possible underlying CLL.
OBJECTIVE: To review the relationship of CLL to cutaneous SCC and to raise awareness of the possible coexistence of these two neoplasms.
METHODS: The case report describes a patient with a SCC of the left cheek treated with Mohs micrographic surgery. A dense lymphocytic infiltrate was noted on the frozen sections, and a complete blood count was obtained.
RESULTS: A lymphocytosis was detected, leading to the diagnosis of CLL, stage 0.
CONCLUSION: Patients with CLL are at an increased risk for the development of cutaneous neoplasms. An infiltrate of leukemic cells in documented CLL patients can be associated with cutaneous neoplasms such as SCC. We present a patient with no known hematologic malignancy who demonstrated a dense lymphocytic infiltrate on Mohs sections. The diagnosis of CLL was considered based on the appearance of this infiltrate. Subsequently, a new case of CLL was confirmed with appropriate testing. The finding of a dense subcutaneous infiltrate of lymphocytes on Mohs frozen sections should raise the possibility of CLL and lead to appropriate screening tests.

PMID: 12828704 [PubMed - indexed for MEDLINE]
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Clin Exp Dermatol. 2002 May;27(3):199-201.

Cutaneous zosteriform squamous cell carcinoma metastasis arising in an immunocompetent patient.

Bauza A, Redondo P, Idoate MA.

Department of Dermatology, University Clinic of Navarra, Pamplona, Spain.

Cutaneous metastases from internal malignancies or primary skin cancers are uncommon, and a zosteriform pattern is very rare. Histologically, these cutaneous metastases usually appear as malignant epithelial cells located throughout the dermis or subcutaneous fat and without connection to the overlying epidermis. The presence of melanocytes in such lesions is atypical. Moreover, although zosteriform cutaneous metastases of cutaneous squamous cell carcinoma have previously been described in immunosuppressed patients, they have not been reported in immunocompetent patients. We report an unusual case of a woman with cutaneous hyperchromic zosteriform metastases, clinically mimicking a metastatic melanoma but appearing histologically as epidermotropic and pigmented metastases of a cutaneous squamous cell carcinoma.

PMID: 12072007 [PubMed - indexed for MEDLINE]
____________

J Cutan Pathol. 1998 Mar;25(3):160-4.

Cutaneous infiltrate of chronic lymphocytic leukemia and relationship to primary cutaneous epithelial neoplasms.

Smoller BR, Warnke RA.

Department of Pathology, Stanford University Medical Center, California

Chronic lymphocytic leukemia involves the skin in a small percentage of patients and may portend an ominous prognosis in some patients. We report a series of eight biopsies from seven different patients in which the cutaneous leukemic infiltrate was confined exclusively to the region immediately surrounding primary epithelial neoplasms including squamous cell carcinoma (6), basal cell carcinoma (1) and actinic keratosis (1). The malignant lymphocytes appear to constitute a host response to these neoplasms and do not appear to suggest a rapid downhill course for these patients. These observations serve to 1) suggest a new pattern of cutaneous involvement by leukemic cells and 2) offer some insights into potential cellular trafficking patterns of these neoplastic cells.

PMID: 9550315 [PubMed - indexed for MEDLINE]
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J Laryngol Otol. 1996 Jul;110(7):694-5.

Aggressive cutaneous squamous cell carcinoma of the head and neck in patients with chronic lymphocytic leukaemia.

Hartley BE, Searle AE, Breach NM, Rhys-Evans PH, Henk JM.

Head and Neck Unit, Royal Marsden Hospital, London, UK.

We describe multiple cutaneous squamous cell carcinomas of the head and neck in five patients with chronic lymphocytic leukaemia (CLL). When associated with CLL, cutaneous squamous cell carcinomata behave in a much more aggressive manner than otherwise expected. Four patients developed local recurrence after primary treatment. All five patients developed lymph node metastases containing squamous cell carcinoma. Three of five patients (60 per cent) had multiple primary lesions. Whereas the increased incidence of second cancers in CLL and notably of skin cancers is documented, little has been written to describe the aggressive behaviour of these tumours. It is important, when treating these patients, to be aware of the high tendency towards local recurrence and lymph node metastasis and to consider an aggressive management plan and careful follow-up.

PMID: 8759553 [PubMed - indexed for MEDLINE]
___________

Ann Dermatol Venereol. 1995;122(1-2):23-5.

Multiple cutaneous carcinoma and chronic lymphoid leukemia

Lippens N, Meunier L, Lavabre T, Navarro M, Barneon G, Meynadier J.

Service de Dermatologie, Hopital Saint-Charles, Montpellier.

INTRODUCTION. Skin cancer occurs more readily in more aggressive forms in immunodepressed subjects. We report the case of a patient with chronic lymphoid leukaemia and multiple skin carcinomas complicated with carcinomatous lymphangitis.
CASE REPORT. A 63 year-old man with chronic lymphoid leukaemia, stage A in the Binet classification, had multiple epidermoid carcinomas on the trunk and face. The skin tumours were complicated with cervical lymph mode metastases, then a prethoracic carcinomatous lymphangitis with a rapidly fatal clinical course.
DISCUSSION. Chronic lymphoid leukaemia and lymphomas are associated with a high incidence of skin carcinoma. The immunodepression inherent in the haematologic disease would appear to favor aggressive skin cancers. Our case was particularly severe since the carcinomatous lymphangitis was rapidly fatal.

PMID: 7668777 [PubMed - indexed for MEDLINE]
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Hum Pathol. 1988 Dec;19(12):1397-402

Clinicopathologic features of cutaneous squamous cell carcinomas of the head and neck in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma.

Frierson HF Jr, Deutsch BD, Levine PA.

Department of Pathology, University of Virginia Medical Center, Charlottesville, VA

The clinicopathologic features of 32 cutaneous squamous cell carcinomas of the head and neck in 12 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma were examined to determine the frequency of clinically aggressive and histologically poorly differentiated carcinomas in this group of patients. Two thirds of the neoplasms were multiple and 56% were high grade (grade 3 or 4). One of the 12 patients had recurrent carcinoma, two patients had recurrent and metastatic disease, and two patients had metastatic tumor without recurrence. Two patients died of tumor, one patient is alive with extensive recurrent and metastatic disease, and one patient died of an uncertain type of carcinoma. An additional patient with squamous cell carcinoma of the face died of cutaneous squamous cell carcinoma that arose on the chest. This study shows that cutaneous squamous cell carcinomas of the head and neck in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma are often high grade and have the potential for recurrence and metastasis.

PMID: 3056829 [PubMed - indexed for MEDLINE]
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Cutis. 1985 Dec;36(6):467-9.

Multiple cutaneous squamous cell carcinomas in a patient with chronic lymphocytic leukemia.

Fowler JF Jr, Knuckles ML.

A 79-year-old white woman had stasis dermatitis and multiple cutaneous squamous cell carcinomas not only in the exposed areas of the face, neck, and arms, but also on the lower legs in the area of dermatitis. Further evaluation revealed early chronic lymphocytic leukemia. This case illustrates the need to search for an underlying abnormality in patients with multiple or unusual skin cancers and to examine biopsy specimens from suspicious skin lesions in immunocompromised patients.

PMID: 4075840 [PubMed - indexed for MEDLINE]
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J Am Acad Dermatol. 1981 Apr;4(4):446-50.

Aggressive behavior of squamous cell carcinoma in a patient with preceding lymphocytic lymphoma.

Turner JE, Callen JP.

Actinically induced squamous cell carcinomas of the skin (SCC) are generally considered nonaggressive and usually curable tumors. However, in patients with lymphoma or leukemia, these tumors may behave in an extremely aggressive manner. We report a case in which an actinically induced SCC occurred in a patient with preceding lymphocytic lymphoma. The tumor progressed from a localized lesion to an invasive destructive lesion which resulted in death. The occurrence of SCC in patients with lymphoma or leukemia possibly should be more aggressively treated, early in its course.

PMID: 6894457 [PubMed - indexed for MEDLINE]
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J Dermatol Surg Oncol. 1979 Aug;5(8):609-14.

Aggressive biologic behavior of basal- and squamous-cell cancers in patients with chronic lymphocytic leukemia or chronic lymphocytic lymphoma.

Weimar VM, Ceilley RI, Goeken JA.

Three basal- and four squamous-cell carcinomas in seven patients with chronic lymphocytic leukemia or chronic lymphocytic lymphoma recurred repeatedly after conventional treatment, and grew to large sizes. The squamous-cell carcinomas metastasized in all four of the patients so afflicted. Absolute numbers of circulating T lymphocytes were normal in the seven patients, but they had cutaneous anergy to intradermal tests with common antigens and to dinitrochlorobenzene. The following recommendations for management of cutaneous carcinomas in patients with malignant lymphomatoses are made: 1) closer surveillance than for patients with cutaneous cancers but without malignant lymphomatoses, 2) early treatment of actinic keratoses to prevent possible transformation to malignancy, and 3) microscopically controlled excision of basal- or squamous-cell carcinomas larger than 1

PMID: 479446 [PubMed - indexed for MEDLINE]
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